Publications by authors named "Aliyah Pabani"

6 Publications

  • Page 1 of 1

Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials.

Eur J Cancer 2021 Jul 8;151:115-125. Epub 2021 May 8.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: Immuno-oncology (IO)-based therapies have been approved based on randomised clinical trials, yet a significant proportion of real-world patients are not represented in these trials. We sought to compare the outcomes of trial-ineligible vs. -eligible patients with advanced solid tumours treated with first-line (1L) IO therapy.

Patients And Methods: Using the International Metastatic Renal Cell Carcinoma (RCC) Database Consortium and the Alberta Immunotherapy Database, patients with advanced RCC, non-small-cell lung cancer (NSCLC) or melanoma treated with 1L PD-(L)1 inhibition-based therapy were included. Trial eligibility was retrospectively determined as per commonly used exclusion criteria. The outcomes of interest were overall survival (OS), overall response rate (ORR), treatment duration (TD) and time to next treatment (TTNT).

Results: A total of 395 of 1241 (32%) patients were deemed trial-ineligible. The main reasons for ineligibility based on preselected exclusion criteria were Karnofsky performance status <70%/Eastern Cooperative Oncology Group performance status >1 (40%, 158 of 395), brain metastases (32%, 126 of 395), haemoglobin < 9 g/dL (16%, 63 of 395) and estimated glomerular filtration rate <40 mL/min (15%, 61 of 395). Between the ineligible vs. eligible groups, the median OS, ORR, median TD and median TTNT were 10.2 vs. 39.7 months (p < 0.01), 36% vs. 47% (p < 0.01), 2.7 vs. 6.9 months (p < 0.01) and 6.0 vs. 16.8 months (p < 0.01), respectively. Subgroup analyses showed statistically significant inferior OS, TD and TTNT for trial-ineligible vs. -eligible patients across all tumour types. Adjusted hazard ratios for death in RCC, NSCLC and melanoma were 1.84 (95% confidence interval [CI] 1.22-2.77), 2.21 (95% CI 1.58-3.11) and 1.82 (95% CI 1.21-2.74), respectively..

Conclusions: Thirty-two percent of real-world patients treated with contemporary 1L IO-based therapies were ineligible for clinical trials. Although one-third of the trial-ineligible patients responded to treatment, the overall trial-ineligible population had inferior outcomes than trial-eligible patients. These data may guide patient counselling and temper expectations of benefit.
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http://dx.doi.org/10.1016/j.ejca.2021.04.004DOI Listing
July 2021

Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors.

Cancer Med 2021 04 16;10(8):2618-2626. Epub 2021 Mar 16.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.

Background: Metastatic uveal melanoma (MUM) is associated with poor survival and inferior response to immune checkpoint inhibitor (ICI) therapy when compared with metastatic cutaneous melanoma. Currently, prognostic biomarkers are lacking to guide treatment decisions.

Patients And Methods: We conducted a multicenter, retrospective cohort study using a centralized, province-wide cancer database in Alberta, Canada. We identified 37 patients with histologically confirmed MUM who received at least one dose of single-agent pembrolizumab or nivolumab, or combination therapy nivolumab and ipilimumab. A modified immune prognostic index (IPI), based on the previously reported lung immune prognostic index, was used to stratify patients into favorable and poor IPI groups. Survival analyses were conducted using the Kaplan-Meier method and Cox proportional hazards models, adjusting for baseline age (≥60) and ECOG performance status, to assess the associations between IPI and overall survival (OS). Time to treatment failure (TTF) was also assessed using the Kaplan-Meier method. The association between IPI and objective response rate was examined using chi-squared tests. Logistic regression was used to determine the association between IPI and immune-related adverse events (irAEs).

Results: Median OS was 15.6 (range 0.6-57.6) months with 45.9% 1-year survival rate at a median follow-up of 11.8 months. We found that a favorable IPI was significantly associated with OS [median 30.5 (12.0-not reached) months in the favorable IPI group compared with 4.6 (2.1-16.0) months in the poor IPI group (p = 0.001)] (HR=4.81, 95% CI; 1.64-14.10, p = 0.004), TTF [median 5.1 (95% CI; 2.1-10.4) months in the favorable IPI group compared with 3.7 (95% CI; 1.4-6.4) months in the poor IPI group (p = 0.0191)], and irAE (HR=6.67, 95% CI; 1.32-33.69, p = 0.0220).

Conclusions: The modified IPI may be a useful tool in clinical practice for identifying MUM patients who are more likely to experience irAEs and realize a survival benefit from ICI treatment.
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http://dx.doi.org/10.1002/cam4.3784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026925PMC
April 2021

Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial.

Lancet Oncol 2020 06 7;21(6):786-795. Epub 2020 May 7.

Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA. Electronic address:

Background: Approximately 25% of all patients with non-small-cell lung cancer present with resectable stage IB-IIIA disease, and although perioperative chemotherapy is the standard of care, this treatment strategy provides only modest survival benefits. On the basis of the activity of immune checkpoint inhibitors in metastatic non-small-cell lung cancer, we designed a trial to test the activity of the PD-L1 inhibitor, atezolizumab, with carboplatin and nab-paclitaxel given as neoadjuvant treatment before surgical resection.

Methods: This open-label, multicentre, single-arm, phase 2 trial was done at three hospitals in the USA. Eligible patients were aged 18 years or older and had resectable American Joint Committee on Cancer-defined stage IB-IIIA non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1, and a history of smoking exposure. Patients received neoadjuvant treatment with intravenous atezolizumab (1200 mg) on day 1, nab-paclitaxel (100 mg/m) on days 1, 8, and 15, and carboplatin (area under the curve 5; 5 mg/mL per min) on day 1, of each 21-day cycle. Patients without disease progression after two cycles proceeded to receive two further cycles, which were then followed by surgical resection. The primary endpoint was major pathological response, defined as the presence of 10% or less residual viable tumour at the time of surgery. All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT02716038, and is ongoing but no longer recruiting participants.

Findings: Between May 26, 2016, and March 1, 2019, we assessed 39 patients for eligibility, of whom 30 patients were enrolled. 23 (77%) of these patients had stage IIIA disease. 29 (97%) patients were taken into the operating theatre, and 26 (87%) underwent successful R0 resection. At the data cutoff (Aug 7, 2019), the median follow-up period was 12·9 months (IQR 6·2-22·9). 17 (57%; 95% CI 37-75) of 30 patients had a major pathological response. The most common treatment-related grade 3-4 adverse events were neutropenia (15 [50%] of 30 patients), increased alanine aminotransferase concentrations (two [7%] patients), increased aspartate aminotransferase concentration (two [7%] patients), and thrombocytopenia (two [7%] patients). Serious treatment-related adverse events included one (3%) patient with grade 3 febrile neutropenia, one (3%) patient with grade 4 hyperglycaemia, and one (3%) patient with grade 2 bronchopulmonary haemorrhage. There were no treatment-related deaths.

Interpretation: Atezolizumab plus carboplatin and nab-paclitaxel could be a potential neoadjuvant regimen for resectable non-small-cell lung cancer, with a high proportion of patients achieving a major pathological response, and manageable treatment-related toxic effects, which did not compromise surgical resection.

Funding: Genentech and Celgene.
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http://dx.doi.org/10.1016/S1470-2045(20)30140-6DOI Listing
June 2020

The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors.

Cancers (Basel) 2019 Nov 2;11(11). Epub 2019 Nov 2.

Department of Oncology, University of Calgary, Calgary, Alta T2N 4N2, Canada.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of several solid tumor types. However, as patient outcomes are heterogeneous, clinical tools to aid in prognostication are needed. The Lung Immune Prognostic Index (LIPI) correlates with outcomes in patients with non-small cell lung cancer (NSCLC) treated with ICI, but its applicability beyond NSCLC is poorly defined. We sought to determine whether LIPI is associated with overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in a pooled, real-world, retrospective cohort of patients with solid tumors treated with ICI. Of the total pooled cohort (N = 578), 47.2%, 38.2% and 14.5% of patients were stratified into good, intermediate and poor LIPI group, respectively. Median OS were 22.8 (95% CI 17.4-29.5), 7.8 (95% CI 6.6-9.6), and 2.5 months (95% CI 1.4-3.4) (p < 0.0001). Median PFS were 9.9 (95% CI 7.2-11.5), 3.6 (95% CI 2.7-4.3), and 1.4 months (95% CI 1.2-2.2) (p < 0.0001). ORR was also associated with LIPI group (p < 0.001). Intermediate and poor LIPI were independently prognostic of OS compared to good LIPI, with hazard ratios (HR) of 1.8 (95% CI 1.4-2.3, p < 0.001) and 3.6 (95% CI 2.5-5.1, p < 0.001), respectively. These data are the first to suggest that in a real-world setting, the prognostic value of LIPI may be tumor agnostic.
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http://dx.doi.org/10.3390/cancers11111713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896022PMC
November 2019

Treatment Outcomes of Immune-Related Cutaneous Adverse Events.

J Clin Oncol 2019 10 19;37(30):2746-2758. Epub 2019 Jun 19.

Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics.

Methods: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed.

Results: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype ( = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 0.71; < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; = .043).

Conclusion: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.
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http://dx.doi.org/10.1200/JCO.18.02141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001790PMC
October 2019

Management Strategies for Early-Onset Pulmonary Events Associated with Brigatinib.

J Thorac Oncol 2019 09 18;14(9):1547-1555. Epub 2019 May 18.

University of California San Diego, Moores Cancer Center, La Jolla, California.

Introduction: Rare cases of early-onset pulmonary events (EOPEs) occurring within days of the start of administration of brigatinib have been reported (incidence 3%-6% with use of the recommended dose of 90 mg for 7 days and then a 180-mg step-up dosing regimen). Current prescribing information suggests dose interruption and then dose reduction for grade 1 or 2 events and discontinuation for recurrent or higher grade events. However, clinical experience suggests that alternative strategies exist to safely maintain dosing.

Methods: Case vignettes illustrating different EOPE clinical scenarios were assembled; they included (1) successful treatment through the initial EOPE, (2) successful rechallenge after the EOPE, (3) successful rechallenge after the EOPE with utilization of a shallower step-up regimen, and (4) unsuccessful rechallenge.

Results: Rapid tolerization to EOPEs within 5 to 8 days may occur with continued dosing, suggesting that dose interruption could be avoided with close observation and temporary supportive care (including supplemental oxygen). If dose interruption occurs, restarting administration of brigatinib at 30 mg, followed by dose increases in 30-mg increments every 3 days to the full dose as tolerated ("shallow step-up dosing") may maximize safety during rechallenge. As compromised baseline respiratory function may increase the rate of clinically apparent EOPEs, proactive use of shallow step-up dosing could be considered in select cases.

Conclusions: Clinically apparent EOPEs are a rare complication of brigatinib. They occur within days of starting administration of the drug, with rapid tolerization possible during continued dosing. Adapting the EOPE nomenclature to include the word transient (TEOPE) may further clinician and patient understanding in distinguishing these events from the pneumonitis seen with other tyrosine kinase inhibitors. Improved education and appropriate supportive care and dosing should allow more patients to maximally and safely benefit from brigatinib.
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http://dx.doi.org/10.1016/j.jtho.2019.04.028DOI Listing
September 2019