Publications by authors named "Phillip Parente"

47 Publications

Real-world use of first-generation antiandrogens: impact on patient outcomes and subsequent therapies in metastatic castration-resistant prostate cancer.

BJU Int 2021 10;128 Suppl 1:18-26

Walter and Eliza Hall Institute, Melbourne, Vic., Australia.

Objectives: To investigate the recent real-world use of first-generation antiandrogens (FGAs) in metastatic castration-resistant prostate cancer (mCRPC) using a retrospective multicentre cohort study.

Patients And Methods: The electronic CRPC Australian Database (ePAD) was interrogated to identify patients with mCRPC. Clinicopathological features, treatment and outcome data, stratified by FGA use, were retrieved and reported through descriptive statistics. Survival analyses were calculated using the Kaplan-Meier method and groups compared using log-rank tests. Factors influencing overall survival (OS) were analysed using Cox proportional hazards regression model.

Results: We identified 634 patients with mCRPC, enrolled in ePAD between January 2016 and March 2019, including 322 (51%) who received FGAs. The median follow-up was 21.9 months. Patients treated with FGAs were more likely to have lower International Society of Urological Pathologists (ISUP) grade group (P = 0.04), longer median time to CRPC (25.6 vs 16.0 months, P < 0.001), and were less likely to have visceral metastases (5.0% vs 11.2%, P = 0.005) or to have received upfront docetaxel (P < 0.001). A ≥50% reduction from pre-treatment prostate-specific antigen (PSA) level (PSA50 response) during FGA treatment occurred in 119 (37%) patients and was independently associated with improved OS (hazard ratio 0.233, P < 0.001). Prior FGA treatment did not significantly influence the selection of subsequent life-prolonging treatments for mCRPC or their PSA50 response rates.

Conclusion: In our present cohort, FGAs were commonly used in lower-risk mCRPC and their use did not significantly influence the choice or duration of subsequent systemic therapy. A PSA50 response to FGA therapy was an independent favourable prognostic marker associated with improved OS.
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http://dx.doi.org/10.1111/bju.15364DOI Listing
October 2021

Avelumab Combined with Stereotactic Ablative Body Radiotherapy in Metastatic Castration-resistant Prostate Cancer: The Phase 2 ICE-PAC Clinical Trial.

Eur Urol 2021 Sep 4. Epub 2021 Sep 4.

Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address:

Background: Immune checkpoint inhibitor monotherapy in metastatic castration-resistant prostate cancer (mCRPC) has produced modest results. High-dose radiotherapy may be synergistic with checkpoint inhibitors.

Objective: To evaluate the efficacy and safety of the PD-L1 inhibitor avelumab with stereotactic ablative body radiotherapy (SABR) in mCRPC.

Design, Setting, And Participants: From November 2017 to July 2019, this prospective phase 2 study enrolled 31 men with progressive mCRPC after at least one prior androgen receptor-directed therapy. Median follow-up was 18.0 mo.

Intervention: Avelumab 10 mg/kg intravenously every 2 wk for 24 wk (12 cycles). A single fraction of SABR (20 Gy) was administered to one or two disease sites within 5 d before the first and second avelumab treatments.

Outcomes Measurements And Statistical Analysis: The primary endpoint was the disease control rate (DCR), defined as a confirmed complete or partial response of any duration, or stable disease/non-complete response/non-progressive disease for ≥6 mo (Prostate Cancer Clinical Trials Working Group 3-modified Response Evaluation Criteria in Solid Tumours version 1.1). Secondary endpoints were the objective response rate (ORR), radiographic progression-free survival (rPFS), overall survival (OS), and safety. DCR and ORR were calculated using the Clopper-Pearson exact binomial method.

Results And Limitations: Thirty-one evaluable men were enrolled (median age 71 yr, 71% with ≥2 prior mCRPC therapy lines, 81% with >5 total metastases). The DCR was 48% (15/31; 95% confidence interval [CI] 30-67%) and ORR was 31% (five of 16; 95% CI 11-59%). The ORR in nonirradiated lesions was 33% (four of 12; 95% CI 10-65%). Median rPFS was 8.4 mo (95% CI 4.5-not reached [NR]) and median OS was 14.1 mo (95% CI 8.9-NR). Grade 3-4 treatment-related adverse events occurred in six patients (16%), with three (10%) requiring high-dose corticosteroid therapy. Plasma androgen receptor alterations were associated with lower DCR (22% vs 71%, p = 0.13; Fisher's exact test). Limitations include the small sample size and the absence of a control arm.

Conclusions: Avelumab with SABR demonstrated encouraging activity and acceptable toxicity in treatment-refractory mCRPC. This combination warrants further investigation.

Patient Summary: In this study of men with advanced and heavily pretreated prostate cancer, combining stereotactic radiotherapy with avelumab immunotherapy was safe and resulted in nearly half of patients experiencing cancer control for 6 months or longer. Stereotactic radiotherapy may potentially improve the effectiveness of immunotherapy in prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.08.011DOI Listing
September 2021

Real-world incidence of symptomatic skeletal events and bone-modifying agent use in castration-resistant prostate cancer - an Australian multi-centre observational study.

Eur J Cancer 2021 11 31;157:485-492. Epub 2021 Jul 31.

Eastern Health, Melbourne, Australia; Monash University, Melbourne, Australia; Weston Park Cancer Centre, Sheffield, United Kingdom. Electronic address:

Introduction: Bone metastases occur frequently in castration-resistant prostate cancer (CRPC) and may lead to skeletal-related events (SREs), including symptomatic skeletal events (SSEs). Bone-modifying agents (BMAs) delay SREs and SSEs. However, the real-world use of BMAs is debated given the absence of demonstrated survival advantage and potential adverse events (AEs). Our retrospective study examined BMA use and SSE rates in Australian patients with CRPC.

Methods: Patients with CRPC and bone metastases were identified from the electronic CRPC Australian Database. Patient characteristics, treatment patterns and AEs were analysed. Descriptive statistics reported baseline characteristics, SSE rates and BMA use. Comparisons between groups used t-tests and Chi-square analyses. Overall survival was calculated by the Kaplan-Meier method.

Results: A total of 532 eligible patients were identified with a median age of 73 years (range: 44-97 years). BMAs were prescribed in 232 men (46%), 183 of whom received denosumab. Patients receiving first-line docetaxel for CRPC were more likely to commence BMAs than those receiving abiraterone or enzalutamide (51% vs 31% vs 38%; p = 0.004). SSEs occurred in 148 men (28%), most commonly symptomatic lesions requiring intervention (75%). At the time of initial SSEs, only 28% were receiving BMAs. Patients treated at sites with lower BMA use (
Conclusion: In our real-world cohort, SSEs occurred in almost one-third of patients with CRPC and bone metastases, whereas less than half of patients received BMAs. The lower rate of SSEs in treatment sites with increased BMA use supports their benefit in this setting.
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http://dx.doi.org/10.1016/j.ejca.2021.06.005DOI Listing
November 2021

Loss of in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy.

JCO Precis Oncol 2021 Jun 22;5. Epub 2021 Jun 22.

Department of Surgery, University of Melbourne, Parkville, Victoria, Australia.

Purpose: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition.

Methods: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing.

Results: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for , a key regulator of EMT reprogramming.

Conclusion: We show that EMT characterizes acutely resistant prostate tumors and that deletion of , a key transcriptional regulator of EMT, correlates with clinical response.
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http://dx.doi.org/10.1200/PO.20.00337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238292PMC
June 2021

Independent prognostic impact of plasma NCOA2 alterations in metastatic castration-resistant prostate cancer.

Prostate 2021 Sep 12;81(13):992-1001. Epub 2021 Jul 12.

Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.

Background: The androgen receptor (AR) pathway-associated gene nuclear receptor coactivator 2 (NCOA2) has an established oncogenic role in early prostate cancer and likewise is a driver of metastatic disease and castration-resistant prostate cancer. However, its significance as a biomarker in metastatic castration-resistant prostate cancer (mCRPC), both alone and in conjunction with co-occurring AR alterations using a liquid biopsy approach has not been investigated.

Methods: Ninety-one patients were included in this study, (n = 68 receiving an androgen receptor pathway inhibitor and n = 23 receiving taxane chemotherapy). Up to 30 ml of peripheral blood was collected before commencing treatment from each patient. Plasma cell-free DNA, along with a matched germline sample, underwent targeted next-generation sequencing using a validated, highly sensitive in-house prostate cancer panel. Variants in AR and NCOA2 were identified and correlated with clinical outcomes.

Results: Plasma AR and NCOA2 aberrations were identified in 35% and 13% of the cohort, respectively, whilst 8% had concurrent AR and NCOA2 alterations. NCOA2 copy number gain and any NCOA2 aberration predicted for lower prostate-specific antigen (PSA) response rates. Likewise, median overall survival was shorter for NCOA2 gain (10.1 vs. 18.3 months; p = .004), remaining significant after adjusting for covariates including circulating tumor DNA fraction and tumor suppressor gene alterations. Importantly, dual AR and NCOA2 aberrations were also associated with inferior outcomes, including no PSA responses in patients treated with AR pathway inhibitors (0% vs. 64%; p = .02).

Conclusions: These data highlight the importance of identifying multiple markers of AR pathway modulation in mCRPC and represent the first instance of the assessment of plasma NCOA2 status as a prognostic biomarker for standard-of-care therapies. Further assessment is warranted to determine if NCOA2 aberrations are a marker of primary resistance to AR pathway inhibitors.
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http://dx.doi.org/10.1002/pros.24194DOI Listing
September 2021

Whole blood expression as a prognostic biomarker in metastatic hormone-sensitive and castration-resistant prostate cancer.

Transl Androl Urol 2021 Apr;10(4):1688-1699

Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.

Background: As potent systemic therapies transition earlier in the prostate cancer disease course, molecular biomarkers are needed to guide optimal treatment selection for metastatic hormone-sensitive prostate cancer (mHSPC). The value of whole blood RNA to detect candidate biomarkers in mHSPC remains largely undefined.

Methods: In this cohort study, we used a previously optimised whole blood reverse transcription polymerase chain reaction assay to assess the prognostic utility [measured by seven-month undetectable prostate-specific antigen (PSA) and time to castration-resistance (TTCR)] of eight prostate cancer-associated gene transcripts in 43 mHSPC patients. Transcripts with statistically significant associations (P<0.05) were further investigated in a metastatic castration-resistant prostate cancer (mCRPC) cohort (n=119) receiving contemporary systemic therapy, exploring associations with PSA >50% response (PSA), progression-free survival (PFS) and overall survival (OS). Clinical outcomes were prospectively collected in a protected digital database. Kaplan-Meier estimates and multivariable Cox proportional-hazards models assessed associations between gene transcripts and clinical outcomes (mHSPC covariates: disease volume, docetaxel use and haemoglobin level; mCRPC covariates: prior exposure to chemotherapy or ARPIs, haemoglobin, performance status and presence of visceral disease). Follow-up was performed monthly during ARPI treatment, three-weekly during taxane chemotherapy, and three-monthly during androgen deprivation therapy (ADT) monotherapy. Serial PSA measurements were performed before each follow-up visit and repeat imaging was at the discretion of the investigator.

Results: Detection of circulating Grainyhead-like 2 () transcript was associated with poor outcomes in mHSPC and mCRPC patients. Detectable expression in mHSPC was associated with a lower rate of seven-month undetectable PSA levels (25% 65%, P=0.059), and independently associated with shorter TTCR (HR 7.3, 95% CI: 1.5-36, P=0.01). In the mCRPC cohort, expression predicted significantly lower PSA response rates (46% 69%, P=0.01), and was independently associated with shorter PFS (HR 3.1, 95% CI: 1.8-5.2, P<0.001) and OS (HR 2.9, 95% CI: 1.6-5.1, P<0.001). Associations were most apparent in patients receiving ARPIs.

Conclusions: Detectable circulating was a negative prognostic biomarker in our mHSPC and mCRPC cohorts. These data support further investigation of as a candidate prognostic biomarker in metastatic prostate cancer, in addition to expanding efforts to better understand a putative role in therapeutic resistance to AR targeted therapies.
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http://dx.doi.org/10.21037/tau-20-1444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100842PMC
April 2021

Predictors of real-world utilisation of docetaxel combined with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer.

Intern Med J 2021 Mar 12. Epub 2021 Mar 12.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Background: Docetaxel has emerged as a standard-of-care for metastatic hormone-sensitive prostate cancer (mHSPC). Uptake of docetaxel for mHSPC in Australia has not previously been reported.

Aims: i) To investigate the real-world uptake of docetaxel in mHSPC; and ii) To identify predictors of utilisation of Docetaxel in mHSPC.

Methods: Men diagnosed from June 2014 to December 2018 and enrolled in the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic) were included. Data collected includes demographics, diagnosis method and institution, staging investigations, and treatments within 12 months of diagnosis. Wilcoxon rank-sum, chi-square and trend tests were used to identify predictors of docetaxel utilisation. All predictors were entered as covariates simultaneously into a multivariable logistic regression model. Statistical significance was set at 0.05 (two-sided).

Results: 1014 men with mHSPC were analysed, 25% of whom received docetaxel with androgen deprivation therapy (ADT). Uptake of docetaxel increased from 20% in 2014 to 33% in 2018. Predictors of higher usage of docetaxel were younger age and treatment in a private hospital, with both remaining significant on multivariable analysis. Notably, the proportion of men under 70 receiving docetaxel increased from 54% in 2014-15 to 64% in 2016-18, while in men aged 70 and over the comparative figures were 15% and 22% respectively.

Conclusions: Although docetaxel was not used in a majority of cases, there was a clear increase in docetaxel uptake especially in younger men following publication of the CHAARTED and STAMPEDE trials. Identifying barriers to real-world implementation of pivotal clinical trial data is critical to improving outcomes in mHSPC. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15288DOI Listing
March 2021

Treatment outcomes for patients with metastatic castrate-resistant prostate cancer following docetaxel for hormone-sensitive disease.

Asia Pac J Clin Oncol 2021 Feb 24;17(1):36-42. Epub 2020 Sep 24.

Olivia Newton-John Cancer Wellness and Research Centre, Melbourne, Australia.

Aim: Optimal treatment for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) has evolved, with many patients deriving benefit from the addition of docetaxel to androgen deprivation therapy (D-ADT). This study sought to define the therapy used and associated activity following D-ADT.

Methods: Retrospective analysis of patients with mHSPC treated with one or more cycles of D-ADT who were identified from a prospectively maintained multisite prostate cancer database of patients treated in a community or academic center setting in Australia. The primary endpoint of this study was first-line time to treatment failure (1L TTF) for subsequent treatment of metastatic Castrate Resistant Prostate Cancer (mCRPC), with secondary endpoints of prostate-specific antigen (PSA) reduction >50% and time from 1L to second-line (2L) treatment initiation.

Results: A total of 93 patients received D-ADT for mHSPC, 85 (91%) had subsequent treatment for mCRPC. Median time to mCRPC (biochemical, clinical or radiographic) had been 14.8 months (95% confidence interval [CI], 11.9-16.5). 1L treatment was enzalutamide 47 patients (55%), abiraterone 23 (27%), cabazitaxel 7 (8%), docetaxel 4 (5%) and other therapies 4 (5%). Median 1L TTF was 6.3 months (95% CI, 4.9-7.6), PSA > 50% reduction was achieved in 32 of 89 patients (36%), median time from 1L to second-line treatment was 7.3 months (1.3-27.4), which did not differ significantly between treatment groups.

Conclusions: Abiraterone, enzalutamide, cabazitaxel and docetaxel all demonstrate activity following progression on D-ADT. No difference in efficacy was detected between treatment options for mCRPC. Prospective trials investigating the optimal treatment sequence for prostate cancer following progression on D-ADT needed.
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http://dx.doi.org/10.1111/ajco.13447DOI Listing
February 2021

Towards new models of cancer care in Australia: lessons from Victoria's response to the COVID-19 pandemic.

Intern Med J 2020 Oct 20;50(10):1282-1285. Epub 2020 Sep 20.

Department of Oncology, Monash University and Monash Health, Melbourne, Victoria, Australia.

In response to the COVID-19 pandemic, the Department of Health and Human Services Victoria (DHHS), the Monash Partners Comprehensive Cancer Consortium (MPCCC) and Victorian Comprehensive Cancer Centre (VCCC) pooled their combined infrastructure to establish the Victorian COVID-19 Cancer Network (VCCN) backed by a Taskforce of expert members. In a few short months, this state-wide clinical network implemented a number of new models of care including clinics to manage acutely presenting cancer patients away from emergency departments, chemotherapy in the home, telehealth models and addressing sustainability of clinical trials.
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http://dx.doi.org/10.1111/imj.15012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537092PMC
October 2020

The Victorian Lung Cancer Service Redesign Project: Impacts of a Quality Improvement collaborative on timeliness and management in lung cancer.

Intern Med J 2020 Sep 8. Epub 2020 Sep 8.

Department of Respiratory Medicine, Alfred Hospital, Melbourne.

Objectives: This initiative targeted Quality Improvement (QI) in lung cancer management, engaging a Quality Improvement collaborative using service redesign methodologies in five Victorian hospitals. QI targets included timeliness from referral and diagnosis to treatment, Multi-Disciplinary meeting (MDM) presentation and supportive care screening. Redesign strategies targeted process sustainability through enhanced team capability.

Designs: Prospective quality improvement cohort study with 6-month pre-intervention period and 6-month redesign implementation period, between September 2016 and August 2017, evaluated using Interrupted Time Series (ITS) analysis.

Setting: Three regional and two metropolitan hospitals in Victoria.

Participants: Newly diagnosed, tissue confirmed lung cancer.

Intervention: Site specific quality improvement service redesign.

Main Outcome Measures: Time intervals from Referral to First Specialist Appointment (FSA), Referral to Diagnosis, Diagnosis to First Treatment (any intent), MDM documented in medical records and Supportive Care Screening Tool (SCST) documented in medical records.

Results: There was a marked reduction in referral to FSA interval across all sites, with median (IQR) falling from 6 (0-15) to 4 (1-10) days, and proportion seen by a specialist within 14 days increased from 74.3% to 84.2%. The interval between diagnosis to treatment was not substantively changed in the 6-month implementation period. The proportion of subjects with documented presentation to the MDM increased from 61% to 67%. The proportion for whom supportive care screening documentation remained low at 26.3% post-intervention.

Conclusions: Data driven redesign initiatives enable identification and analysis of clinical practice variation and may be utilised to enhance timeliness of cancer care and improve local data service capabilities. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15043DOI Listing
September 2020

Prognostic Impact of Total Plasma Cell-free DNA Concentration in Androgen Receptor Pathway Inhibitor-treated Metastatic Castration-resistant Prostate Cancer.

Eur Urol Focus 2020 Jul 29. Epub 2020 Jul 29.

Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Electronic address:

Total plasma cell-free DNA (cfDNA) levels were recently shown to be prognostic in two large phase III trials of taxane chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). However, whether cfDNA concentration is predictive of treatment outcomes with androgen receptor pathway inhibitors (ARPIs) is unknown. We quantified plasma cfDNA levels at baseline (n = 74) and 4 weeks on treatment (n = 56) in a prospective cohort of mCRPC patients treated with the ARPIs abiraterone acetate or enzalutamide. Elevated total cfDNA concentration (log) at both baseline (hazard ratio [HR] 5.5, p < 0.001) and week 4 (HR 7.5, p < 0.001) was a significant negative prognostic factor for overall survival (OS), a finding maintained after adjustment for plasma circulating tumour DNA fraction. Unexpectedly, a rise in cfDNA concentration from baseline to week 4 was also associated with significantly improved OS (HR 0.14, p = 0.003). Conversely, patients with ≥29.8% decrease in cfDNA from baseline (optimal cut-point) had significantly shorter median OS than the rest of the cohort (10.5 vs 25.7 mo, p = 0.03). Collectively, our findings point to the potential prognostic utility of quantifying cfDNA in mCRPC and in particular suggest that dynamic changes in total cfDNA levels may be a novel early predictive biomarker for therapeutic outcome in ARPI-treated patients. PATIENT SUMMARY: We measured the levels of total cell-free DNA (cfDNA) in the plasma of patients with metastatic prostate cancer prior to and 4 weeks after starting new hormonal drugs. We found that patients with higher levels of cfDNA or a higher proportion of tumour-derived DNA at baseline had worse outcomes on hormonal therapies. Similarly, higher levels of cfDNA at 4 weeks into therapy were also associated with worse outcomes. However, a rise in total cfDNA levels at 4 weeks compared with baseline was linked with better outcomes. Measuring changes in cfDNA concentration may be a useful and technically straightforward early way to predict how patients will respond to treatment in metastatic prostate cancer.
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http://dx.doi.org/10.1016/j.euf.2020.07.001DOI Listing
July 2020

Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors.

J Clin Oncol 2020 07 17;38(19):2140-2150. Epub 2020 Mar 17.

Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.

Purpose: Lifirafenib is an investigational, reversible inhibitor of B-RAF, wild-type A-RAF, B-RAF, C-RAF, and EGFR. This first-in-human, phase I, dose-escalation/dose-expansion study evaluated the safety, tolerability, and efficacy of lifirafenib in patients with - or -mutated solid tumors.

Methods: During dose escalation, adult patients with histologically/cytologically confirmed advanced solid tumors received escalating doses of lifirafenib. Primary end points were safety/tolerability during dose escalation and objective response rate in preselected patients with and mutations during dose expansion.

Results: The maximum tolerated dose was established as 40 mg/d; dose-limiting toxicities included reversible thrombocytopenia and nonhematologic toxicity. Across the entire study, the most common grade ≥ 3 treatment-emergent adverse events were hypertension (n = 23; 17.6%) and fatigue (n = 13; 9.9%). One patient with -mutated melanoma achieved complete response, and 8 patients with mutations had confirmed objective responses: melanoma (n = 5, including 1 patient treated with prior B-RAF/MEK inhibitor therapy), thyroid cancer/papillary thyroid cancer (PTC; n = 2), and low-grade serous ovarian cancer (LGSOC; n = 1). One patient with -mutated non-small-cell lung cancer (NSCLC) had unconfirmed partial response (PR). Patients with -mutated endometrial cancer and codon 12-mutated NSCLC had confirmed PR (n = 1 each). No responses were seen in patients with -mutated colorectal cancer (n = 20).

Conclusion: Lifirafenib is a novel inhibitor of key RAF family kinases and EGFR, with an acceptable risk-benefit profile and antitumor activity in patients with -mutated solid tumors, including melanoma, PTC, and LGSOC, as well as -mutated NSCLC and endometrial carcinoma. Future comparisons with first-generation B-RAF inhibitors and exploration of lifirafenib alone or as combination therapy in patients with selected mutations who are resistant/refractory to first-generation B-RAF inhibitors are warranted.
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http://dx.doi.org/10.1200/JCO.19.02654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325368PMC
July 2020

Outcomes of a randomized controlled trial assessing a smartphone Application to reduce unmet needs among people diagnosed with CancEr (ACE).

Cancer Med 2020 01 25;9(2):507-516. Epub 2019 Nov 25.

Faculty of Health, School of Psychology, Deakin University, Geelong, Vic., Australia.

Background: Smartphone technology represents an opportunity to deliver practical solutions for people affected by cancer at a scale that was previously unimaginable, such as information, appointment monitoring, and improved access to cancer support services. This study aimed to determine whether a smartphone application (app) reduced the unmet needs among people newly diagnosed with cancer.

Methods: A single blind, multisite randomized controlled trial to determine the impact of an app-based, 4-month intervention. Newly diagnosed cancer patients were approached at three health service treatment clinics.

Results: Eighty-two people were randomized (intervention; n = 43 and control; n = 39), average age was 59.5 years (SD: 12.9); 71% female; 67% married or in a de facto relationship. At baseline, there were no differences in participants' characteristics between the groups. No significant effects, in reducing unmet needs, were demonstrated at the end of intervention (4-month) or 12-month follow-up. Overall, 94% used the app in weeks 1-4, which decreased to 41% in weeks 13-16. Mean app use time per participant: Cancer Information, 6.9 (SD: 18.9) minutes; Appointment Schedule, 5.1 (SD: 9.6) minutes; Cancer Services 1.5 minutes (SD: 6.8); Hospital Navigation, 1.4 (SD: 2.8) minutes.

Conclusions: Despite consumer involvement in the design of this smartphone technology, the app did not reduce unmet needs. This may have been due to the study being underpowered. To contribute to a meaningful understanding and improved implementation of smartphone technology to support people affected by cancer, practical considerations, such as recruitment issues and access to, and confidence with, apps, need to be considered. Australian New Zealand Clinical Trials Registration (ACTRN) Trial Registration: 12616001251415; WEF 7/9/2016.
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http://dx.doi.org/10.1002/cam4.2718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970035PMC
January 2020

Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma.

Pigment Cell Melanoma Res 2020 03 2;33(2):358-365. Epub 2019 Nov 2.

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.

The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment-naïve and 22% failed first-line BRAF/MEK inhibitors. Treatment-related adverse events occurred in 67% of patients, grade 3-5 in 38%. The overall objective response rate was 41%, 57% in treatment-naïve and 21% in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95% CI, 3.0-6.0) in the whole cohort, 11.0 months (95% CI, 6.0-NR) in treatment-naïve and 2.0 months (95% CI, 1.4-4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real-world population. While first-line efficacy appears comparable to trial populations, BRAF-mutant patients failing prior BRAF/MEK inhibitors show less response.
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http://dx.doi.org/10.1111/pcmr.12831DOI Listing
March 2020

Prognostic Utility of a Whole-blood Androgen Receptor-based Gene Signature in Metastatic Castration-resistant Prostate Cancer.

Eur Urol Focus 2021 01 15;7(1):63-70. Epub 2019 May 15.

Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. Electronic address:

Background: The treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly in recent years. Identifying predictive and/or prognostic biomarkers in the context of this rapidly expanding therapeutic armamentarium remains a pressing and unmet clinical need.

Objective: To develop a prognostic whole-blood gene signature for mCRPC patients.

Design, Setting, And Participants: As part of an ongoing prospective, multicentre biomarker research study (Australian Prostate Biomarker Alliance), we enrolled 115 mCRPC patients commencing chemotherapy (n = 34) or androgen receptor (AR) pathway inhibitors therapy (n = 81) and obtained pretreatment whole-blood samples in PAXgene RNA tubes. Gene expression was assessed using reverse transcription-polymerase chain reaction.

Outcome Measurements And Statistical Analysis: Gene transcripts correlating with overall survival (OS) at p < 0.10 in univariate Cox regression models were incorporated into a multigene signature. Kaplan-Meier survival estimates and multivariate analyses were used to assess association with clinical outcomes. Prognostic strength of the signature was estimated using a concordance probability estimate (CPE).

Results And Limitations: Based on univariate analysis for OS, the following genes were incorporated into a multigene signature: AR splice variant 7 (AR-V7), and three androgen-regulated genes: GRHL2, HOXB13, and FOXA1. The number of positive transcripts clearly stratified survival outcomes (median OS: not reached vs 24.8 mo vs 16.2 mo for 0, 1, and ≥2 transcripts, respectively; p = 0.0052). Notably, this multigene signature retained prognostic significance on multivariable analysis (hazard ratio, 2.1; 95% confidence interval, 1.1-4.0; p = 0.019). Moreover, CPE for this model was 0.78, indicating strong discriminative capacity. Limitations include short follow-up time.

Conclusions: Our data demonstrate the prognostic utility of a novel whole-blood AR-based signature in mCRPC patients commencing contemporary systemic therapies. Our pragmatic assay requires minimal processing, can be performed in most hospital laboratories, and could represent a key prognostic tool for risk stratification in mCRPC.

Patient Summary: We found that expression of certain genes associated with the androgen receptor could help determine how long men with advanced prostate cancer survive after starting modern drug therapies.
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http://dx.doi.org/10.1016/j.euf.2019.04.020DOI Listing
January 2021

Patterns of care for stage III non-small cell lung cancer in Australia.

Asia Pac J Clin Oncol 2019 Jun 14;15(3):93-100. Epub 2019 Mar 14.

St Vincent's Hospital and Kinghorn Cancer Centre, Darlinghurst, NSW, Australia.

Stage III non-small cell lung cancer (NSCLC) makes up a third of all NSCLC cases and is potentially curable. Despite this 5-year survival rates remain between 15% and 20% with chemoradiation treatment alone given with curative intent. With the recent exciting breakthroughs in immunotherapy use (durvalumab) for stage III NSCLC, further improvements in patient survival can be expected. Most patients with stage III NSCLC present initially to their general practitioner (GP). The recommended time from GP referral to first specialist appointment is less than 14 days with treatment initiated within 42 days. Our review found that there is a shortfall in meeting these recommendations, however a number of initiatives have been established in Australia to improve timely and accurate diagnosis and treatment patterns. The lung cancer multidisciplinary team (MDT) is critical to consistency of evidence-based diagnosis and treatment and can improve patient survival. We aimed to review current patterns of care and clinical practice recommendations for stage III NSCLC across Australia and identify opportunities to improve practice in referral, diagnosis and treatment pathways.
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http://dx.doi.org/10.1111/ajco.13140DOI Listing
June 2019

Exploring the spectrum of late effects following radical orchidectomy for stage I testicular seminoma: a systematic review of the literature.

Support Care Cancer 2019 Feb 22;27(2):373-382. Epub 2018 Oct 22.

Eastern Health Cancer Services, Level 4, 8 Arnold St., Box Hill, VIC, 3128, Australia.

Purpose: Testicular seminomas occur in young men and are highly curable. Toxicities following treatment for men with extensive stage II-III seminomas may cause long-term morbidities. However, it is not clear whether the risk of late effects also increases following surgery for testis-confined seminoma. In this systematic review, we examined the available literature regarding the incidence of late effects in our target population of patients with stage I seminoma treated with orchidectomy alone.

Method: Publications were identified through an electronic literature search using the MEDLINE, EMBASE and PsychInfo databases, identifying cohorts treated for stage I seminoma. Data on late effects were collected and classified as physical or psychological.

Results: Six hundred and four articles were screened to identify 100 studies. In the target population, available evidence suggests no increased risk of cardiovascular disease, metabolic syndrome, or renal dysfunction compared to the general population. Sperm counts were initially lower than an age-matched cohort; however, counts normalised when re-assessed 5 years later. Data were not specifically reported for the target population regarding bone health, second malignancy, hypogonadism, fertility and all psychological domains. Heterogeneity of study design and reporting methods contributed to uncertainty regarding the true incidence and clinical significance of late effects.

Conclusions: The curability of stage I seminoma and the wide range of potential late effects of treatment suggest the need for long-term monitoring alongside standard cancer surveillance. Important data are needed on the prevalence of late effects, specifically related to testicular cancer survivors undergoing surveillance following orchidectomy.

Implications For Cancer Survivors: Awareness and screening for relevant late effects may prevent further morbidity in men treated for stage I seminoma.
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http://dx.doi.org/10.1007/s00520-018-4492-7DOI Listing
February 2019

Motivational interviewing added to oncology rehabilitation did not improve moderate-intensity physical activity in cancer survivors: a randomised trial.

J Physiother 2018 10 11;64(4):255-263. Epub 2018 Sep 11.

School of Allied Health, La Trobe University; Allied Health Clinical Research Office, Eastern Health.

Question: Does adding weekly, physiotherapist-delivered motivational interviewing to outpatient oncology rehabilitation for cancer survivors increase physical activity levels and improve physical and psychosocial outcomes that are typically impaired in this cohort?

Design: Randomised controlled trial with blinded outcome assessment, concealed allocation and intention-to-treat analysis.

Participants: A heterogeneous sample of 46 cancer survivors (n=29 female; mean age 59 years) participating in a public outpatient oncology rehabilitation program.

Intervention: Participants were randomly allocated to receive oncology rehabilitation (n=24) or oncology rehabilitation with motivational interviewing delivered once weekly for 7 weeks via telephone by a physiotherapist (n=22).

Outcome Measures: The primary outcome was amount of physical activity of at least moderate intensity completed in 10-minute bouts, measured by an accelerometer worn continuously for 1 week. Secondary outcomes included other measures of physical activity, sedentary behaviour, physical function, psychosocial function, and quality of life.

Results: When added to oncology rehabilitation, motivational interviewing caused no appreciable increase in the amount of moderate-intensity physical activity (MD -1.2 minutes/day, 95% CI -2.5 to 0.02). Among many secondary outcomes, the only statistically significant result was a small effect on nausea, which probably represents a Type I error. However, several secondary outcomes related to lower-intensity physical activity had non-significant confidence intervals that included large effects such as: sedentary time (SMD -0.67, 95% CI -1.32 to 0.02), light-intensity physical activity (SMD 0.56, 95% CI -0.12 to 1.21) and daily step count (SMD 0.37, 95% CI -0.30 to 1.02).

Conclusion: Adding motivational interviewing to oncology rehabilitation did not increase moderate-intensity physical activity. Favourable trends on measures of lower-intensity physical activity suggest that motivational interviewing should be further investigated for its effects on reducing sedentary time and improving light-intensity physical activity for cancer survivors participating in rehabilitation.

Trial Registration: ANZCTR 12616001079437. [Dennett AM, Shields N, Peiris CL, Prendergast LA, O'Halloran PD, Parente P, Taylor NF (2018) Motivational interviewing added to oncology rehabilitation did not improve moderate-intensity physical activity in cancer survivors: a randomised trial. Journal of Physiotherapy 64: 255-263].
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http://dx.doi.org/10.1016/j.jphys.2018.08.003DOI Listing
October 2018

Does implementation matter if comprehension is lacking? A qualitative investigation into perceptions of advance care planning in people with cancer.

Support Care Cancer 2018 Nov 11;26(11):3765-3771. Epub 2018 May 11.

Faculty of Health, School of Nursing & Midwifery, Deakin University, 1 Gheringhap St, Geelong, VIC, Australia.

Purpose: While advance care planning holds promise, uptake is variable and it is unclear how well people engage with or comprehend advance care planning. The objective of this study was to explore how people with cancer comprehended advance care plans and examine how accurately advance care planning documentation represented patient wishes.

Methods: This study used a qualitative descriptive design. Data collection comprised interviews and an examination of participants' existing advance care planning documentation. Participants included those who had any diagnosis of cancer with an advance care plan recorded: Refusal of Treatment Certificate, Statement of Choices, and/or Enduring Power of Attorney (Medical Treatment) at one cancer treatment centre.

Results: Fourteen participants were involved in the study. Twelve participants were female (86%). The mean age was 77 (range: 61-91), and participants had completed their advance care planning documentation between 8 and 72 weeks prior to the interview (mean 33 weeks). Three themes were evident from the data: incomplete advance care planning understanding and confidence, limited congruence for attitude and documentation, advance care planning can enable peace of mind. Complete advance care planning understanding was unusual; most participants demonstrated partial comprehension of their own advance care plan, and some indicated very limited understanding. Participants' attitudes and their written document congruence were limited, but advance care planning was seen as helpful.

Conclusions: This study highlighted advance care planning was not a completely accurate representation of patient wishes. There is opportunity to improve how patients comprehend their own advance care planning documentation.
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http://dx.doi.org/10.1007/s00520-018-4241-yDOI Listing
November 2018

Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study.

BMC Health Serv Res 2018 03 1;18(1):147. Epub 2018 Mar 1.

Medical Oncology Service, Hospital Universitario La Paz (IDIPAZ), Madrid, Spain.

Background: Data are scarce regarding real-world health care resource use (HCRU) for non-small cell lung cancer (NSCLC). An understanding of current clinical practices and HCRU is needed to provide a benchmark for rapidly evolving NSCLC management recommendations and therapeutic options. The objective of this study was to describe real-world HCRU for patients with advanced NSCLC.

Methods: This multinational, retrospective chart review study was conducted at academic and community oncology sites in Italy, Spain, Germany, Australia, Japan, South Korea, Taiwan, and Brazil. Deidentified data were drawn from medical records of 1440 adults (≥18 years old) who initiated systemic therapy (2011 to mid-2013) for a new, confirmed diagnosis of advanced or metastatic (stage IIIB or IV) NSCLC. We summarized HCRU associated with first and subsequent lines of systemic therapy for advanced/metastatic NSCLC.

Results: The proportion of patients who were hospitalized at least once varied by country from 24% in Italy to 81% in Japan during first-line therapy and from 22% in Italy to 84% in Japan during second-line therapy; overall hospitalization frequency was 2.5-11.1 per 100 patient-weeks, depending on country. Emergency visit frequency also varied among countries (overall from 0.3-5.9 per 100 patient-weeks), increasing consistently from first- through third-line therapy in each country. The outpatient setting was the most common setting of resource use. Most patients in the study had multiple outpatient visits in association with each line of therapy (overall from 21.1 to 59.0 outpatient visits per 100 patient-weeks, depending on country). The use of health care resources showed no regular pattern associated with results of tests for activating mutations of the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements.

Conclusions: HCRU varied across countries. These findings suggest differing approaches to the clinical management of advanced NSCLC among the eight countries. Comparative findings and an understanding of country-specific clinical practices can help to identify areas of need and guide future resource allocation for patients with advanced NSCLC. Further studies evaluating the costs associated with resource use are warranted.
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http://dx.doi.org/10.1186/s12913-018-2946-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831211PMC
March 2018

Clinical need for standardised multidisciplinary meeting assessment processes.

Intern Med J 2018 02;48(2):230-231

Department of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/imj.13688DOI Listing
February 2018

Expression of Androgen Receptor Splice Variant 7 or 9 in Whole Blood Does Not Predict Response to Androgen-Axis-targeting Agents in Metastatic Castration-resistant Prostate Cancer.

Eur Urol 2018 06;73(6):818-821

Department of Medicine, School of Clinical Sciences, Monash University, Australia; Department of Medical Oncology, Monash Health, Australia. Electronic address:

In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response. To further investigate, we designed a highly sensitive and specific whole blood assay for detecting AR-V7 and AR-V9. We then examined for a correlation between baseline AR-V7/V9 status and treatment outcome in 37 mCRPC patients commencing abiraterone or enzalutamide. Of the patients, 24% (9/37) were AR-V-positive. Notably, prostate-specific antigen (PSA) response rates did not significantly differ between AR-V-positive (6/9) and AR-V-negative (18/28) patients (66% vs 64%, p=0.9). Likewise, median PSA progression-free survival was not significantly different between AR-V-positive and AR-V-negative patients (9.2 mo vs not reached; p=0.9). These data, which support the findings of the pivotal ARMOR3-SV clinical trial, suggest that baseline AR-V expression does not predict outcomes in mCRPC patients receiving abiraterone or enzalutamide.

Patient Summary: Detection of androgen receptor splice variants (AR-Vs) in circulating tumour cells of advanced prostate cancer patients has been linked to resistance to abiraterone and enzalutamide. We designed a blood test to detect AR-Vs that can be performed more routinely than tests involving circulating tumour cells and found that patients with AR-Vs still benefit from these effective treatments.
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http://dx.doi.org/10.1016/j.eururo.2018.01.007DOI Listing
June 2018

Measuring cancer caregiver health literacy: Validation of the Health Literacy of Caregivers Scale-Cancer (HLCS-C) in an Australian population.

Health Soc Care Community 2018 05 5;26(3):330-344. Epub 2017 Dec 5.

Faculty of Health, Deakin University, Burwood, VIC, Australia.

Caregivers have been largely neglected in health literacy measurement. We assess the construct validity, and internal consistency of the Health Literacy of Caregivers Scale-Cancer (HLCS-C), and present a revised, psychometrically robust scale. Using data from 297 cancer caregivers (12.4% response rate) recruited from Melbourne, Australia between January-July 2014, confirmatory factor analysis (CFA) was conducted to evaluate the HLCS-C's proposed factor structure. Items were evaluated for: item difficulty, unidimensionality and overall item fit within their domain. Item-threshold-ordering was examined though one-parameter Item Response Theory models. Internal consistency was assessed using Raykov's reliability coefficient. CFA results identified 42 poorly performing/redundant items which were subsequently removed. A 10-factor model was fitted to 46 acceptable items with no correlated residuals or factor cross-loadings accepted. Adequate fit was revealed (χ  = 1463.807[df = 944], p < .001, RMSEA = 0.043, CFI = 0.980, TLI = 0.978, WRMR = 1.00). Ten domains were identified: Proactivity and determination to seek information; Adequate information about cancer and cancer management; Supported by healthcare providers (HCP) to understand information; Social support; Cancer-related communication with the care recipient (CR); Understanding CR needs and preferences; Self-care; Understanding the healthcare system; Capacity to process health information; and Active engagement with HCP. Internal consistency was adequate across domains (0.78-0.92). The revised HLCS-C demonstrated good structural, convergent, and discriminant validity, and high internal consistency. The scale may be useful for the development and evaluation of caregiver interventions.
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http://dx.doi.org/10.1111/hsc.12524DOI Listing
May 2018

A case of autosplenectomy associated with T-cell checkpoint inhibitor treatment.

BMJ Case Rep 2017 Oct 19;2017. Epub 2017 Oct 19.

Department of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1136/bcr-2017-220775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665193PMC
October 2017

Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m) and the Currently Approved Dose (25 mg/m) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA.

J Clin Oncol 2017 Oct 15;35(28):3198-3206. Epub 2017 Aug 15.

Mario Eisenberger, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Anne-Claire Hardy-Bessard, Centre Armoricain d'Oncologie, Centre Armoricain de Radiothérapie, d'Imagerie Médicale et d'Oncologie-Hôpital Privé Des Côtes d'Armor, Plérin; Loïc Mourey, Institut Claudius Regaud, l'Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse; Mustapha Chadjaa, Sanofi, Vitry-sur-Seine, France; Choung Soo Kim, Asan Medical Center, Seoul, South Korea; Lajos Géczi, National Institute of Oncology, Budapest, Hungary; Daniel Ford, City Hospital, Cancer Centre at Queen Elizabeth Hospital, Birmingham; Johann de Bono, Prostate Cancer Targeted Therapy Team, Royal Marsden National Health Service Foundation Trust/The Institute of Cancer Research, Sutton, United Kingdom; Joan Carles, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona; Phillip Parente, Eastern Health Clinical School, Monash University, Box Hill Hospital, Melbourne, Victoria, Australia; Albert Font, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Gabriel Kacso, Iuliu Hatieganu Medical University, Amethyst Radiology Therapeutic Center, Cluj, Romania; Wenping Zhang, Sanofi, Bridgewater, NJ; and John Bernard, Sanofi, Cambridge, MA.

Purpose Cabazitaxel 25 mg/m (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25. To claim noninferiority of C20 (maintenance of ≥ 50% of the OS benefit of C25 v mitoxantrone in TROPIC) with 95% confidence level, the upper boundary of the CI of the hazard ratio (HR) for C20 versus C25 could not exceed 1.214 under a one-sided 98.89% CI after interim analyses. Secondary end points included progression-free survival, prostate-specific antigen (PSA), tumor and pain responses and progression, health-related quality of life, and safety. Results Overall, 1,200 patients were randomly assigned (C20, n = 598; C25, n = 602). Baseline characteristics were similar in both arms. Median OS was 13.4 months for C20 and 14.5 months for C25 (HR, 1.024). The upper boundary of the HR CI was 1.184 (less than the 1.214 noninferiority margin). Significant differences were observed in favor of C25 for PSA response (C20, 29.5%; C25, 42.9%; nominal P < .001) and time to PSA progression (median: C20, 5.7 months; C25, 6.8 months; HR for C20 v C25, 1.195; 95% CI, 1.025 to 1.393). Health-related quality of life did not differ between cohorts. Rates of grade 3 or 4 treatment-emergent adverse events were 39.7% for C20 and 54.5% for C25. Conclusion The efficacy of cabazitaxel in postdocetaxel patients with mCRPC was confirmed. The noninferiority end point was met; C20 maintained ≥ 50% of the OS benefit of C25 versus mitoxantrone in TROPIC. Secondary efficacy end points favored C25. Fewer adverse events were observed with C20.
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http://dx.doi.org/10.1200/JCO.2016.72.1076DOI Listing
October 2017

Cabazitaxel in patients with metastatic castration-resistant prostate cancer: safety and quality of life data from the Australian early access program.

Asia Pac J Clin Oncol 2017 Dec 10;13(6):391-399. Epub 2017 May 10.

Westmead Hospital, Sydney, NSW, Australia.

Aim: Cabazitaxel is a next generation taxane that has been shown to improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed during or after docetaxel-based therapy. A worldwide early access program (EAP) study was established to provide access to cabazitaxel ahead of commercial availability and to evaluate its safety and tolerability. The Australian EAP included patient-reported outcomes to evaluate the impact of cabazitaxel on quality of life (QoL). The final safety and QoL results from the Australian EAP for cabazitaxel are reported.

Methods: Australian patients with mCRPC previously treated with a docetaxel-containing regimen received cabazitaxel (25 mg/m ) every 3 weeks plus prednisone/prednisolone (10 mg daily) until disease progression, death, unacceptable toxicity, physician's decision or patient's refusal of further treatment. QoL data was collected using the AQoL-8D questionnaire.

Results: 104 patients from 18 Australian sites (median age at baseline, 70) enrolled in the EAP and completed at least one AQoL-8D questionnaire. Patients received a median of 6 cycles of cabazitaxel. 67 patients (64.4%) experienced grade ≥3 treatment-emergent adverse events (TEAEs); the most frequent TEAEs were neutropenia, febrile neutropenia, diarrhoea, and vomiting. QoL scores remained stable with increasing treatment cycles.

Conclusion: The results suggest that the safety profile cabazitaxel is manageable in the Australian clinical practice setting and that QoL is maintained with little or no detrimental effect of cabazitaxel in patients continuing on treatment without disease progression.
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http://dx.doi.org/10.1111/ajco.12679DOI Listing
December 2017

How accurate are medical oncologists' impressions of management of metastatic colorectal cancer in Australia?

Asia Pac J Clin Oncol 2018 Apr 16;14(2):e167-e174. Epub 2017 Mar 16.

Department of Medical Oncology, Western Hospital, Melbourne, Australia.

Aim: Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC.

Methods: Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice.

Results: Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals.

Conclusions: Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC.
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http://dx.doi.org/10.1111/ajco.12671DOI Listing
April 2018

The impact of bevacizumab in metastatic colorectal cancer with an intact primary tumor: Results from a large prospective cohort study.

Asia Pac J Clin Oncol 2017 Aug 25;13(4):314-321. Epub 2016 Nov 25.

Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.

Background: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood.

Methods: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed.

Results: Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)). Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623. CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.
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http://dx.doi.org/10.1111/ajco.12639DOI Listing
August 2017

Posterior reversible encephalopathy syndrome mimicking brain metastases in a patient with metastatic transitional cell carcinoma.

Asia Pac J Clin Oncol 2017 Oct 11;13(5):e534-e536. Epub 2016 Oct 11.

Eastern Health Clinical School, Monash University, Victoria, Australia.

Posterior reversible encephalopathy syndrome (PRES) has been described in the context of uncontrolled hypertension, eclampsia, renal disease and autoimmune conditions, or in patients treated with chemotherapy or immunosuppressive agents. In contrast, we report the occurrence of PRES in a patient with untreated metastatic transitional cell carcinoma. The case emphasizes important diagnostic challenges associated with atypical presentations without "typical" risk factors and the limitations of common diagnostic imaging modalities. It highlights the ability of nonmalignant conditions like PRES to mimic brain metastases and the importance of magnetic resonance imaging as a diagnostic tool. A high index of suspicion is warranted in atypical presentations, as prompt treatment is imperative to ensure full neurological recovery.
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http://dx.doi.org/10.1111/ajco.12510DOI Listing
October 2017
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