Publications by authors named "Volker Heinemann"

326 Publications

Genetic variants involved in the cGAS-STING pathway predict outcome in patients with metastatic colorectal cancer: Data from FIRE-3 and TRIBE trials.

Eur J Cancer 2022 Jun 21;172:22-30. Epub 2022 Jun 21.

Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address:

Background: The activation of stimulator of interferon genes (STING) was reported to enhance cetuximab-mediated natural killer cell activation and dendritic cell maturation. Polymorphisms in genes in the cyclic GMP-AMP synthase (cGAS)-STING pathway may affect innate immune response. Therefore, we hypothesised that genetic variants in the cGAS-STING pathway may predict the efficacy of cetuximab-based treatment in patients with metastatic colorectal cancer.

Methods: Genomic DNA from blood samples of patients enrolled in FIRE-3 (cetuximab arm, n = 129; bevacizumab arm, n = 107) and TRIBE (bevacizumab arm, n = 215) was genotyped using the OncoArray-500K bead chip panel. Seven selected single nucleotide polymorphisms in 3 genes (cGAS, STING and interferon B1 (IFNB1)) were analysed for the association with overall survival and progression-free survival.

Results: In the cetuximab cohort, patients with STING rs1131769 any T allele showed significantly shorter overall survival (36.3 versus 56.1 months) than carriers of C/C in both univariate [hazard ratio (HR) = 2.08; 95% confidence interval (CI): 1.06-4.07; P = 0.03] and multivariate (HR = 2.98; 95% CI: 1.35-6.6; P = 0.0085) analyses; patients carrying IFNB1 rs1051922 G/A and A/A genotype showed a significantly shorter progression-free survival than carriers of G/G allele in both univariate (G/A versus G/G, 10.2 versus 14.1 months, HR = 1.84; 95% CI 1.23-2.76; A/A versus G/G, 10.7 versus 14.1 months, HR = 2.19; 95% CI 0.97-4.96; P = 0.0077) and multivariate analyses (G/A versus G/G, HR = 2; 95% CI 1.22-3.3; A/A versus G/G, HR = 2.19, 95% CI 0.92-5.26, P = 0.02). These associations were not observed in the bevacizumab arm of FIRE-3 or TRIBE.

Conclusion: These results suggest for the first time that germline polymorphisms in STING and IFNB1 genes may predict the outcomes of cetuximab-based treatment in patients with metastatic colorectal cancer.
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http://dx.doi.org/10.1016/j.ejca.2022.05.016DOI Listing
June 2022

Serum biomarker panel diagnostics in pancreatic ductal adenocarcinoma: the clinical utility of soluble interleukins, IFN-γ, TNF-α and PD-1/PD-L1 in comparison to established serum tumor markers.

J Cancer Res Clin Oncol 2022 Jun 23. Epub 2022 Jun 23.

Munich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University of Munich, Munich, Germany.

Purpose: Novel biomarkers to better predict outcome and select the best therapeutic strategy for the individual patient are necessary for pancreatic ductal adenocarcinoma (PDAC).

Methods: Using a panel assay, multiple biomarkers (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CEA, CA 19-9, CYFRA 21-1, HE4, PD-1 and PD-L1 levels) were measured in serum samples of 162 patients with resected, locally advanced and metastatic PDAC in this retrospective single-center study. Optimal cut-off values to differentiate prognostic subgroups with significantly different overall survival (OS) were determined by receiver operator characteristics and Youden Index analysis. Marker levels were assessed before the start of chemotherapy and correlated with OS by univariate and multivariate Cox analysis.

Results: Median OS for resected patients was 28.2 months, for locally advanced patients 17.9 months and for patients with metastatic disease 8.6 months. CYFRA 21-1 and IL-8 discriminated metastatic from locally advanced patients best (AUC 0.85 and AUC 0.81, respectively). In univariate analyses, multiple markers showed prognostic relevance in the various subgroups. However, multivariate Cox models comprised only CYFRA 21-1 in the resected group (HR 1.37, p = 0.015), IL-10 in locally advanced PDAC (HR 10.01, p = 0.014), as well as CYFRA 21-1 and CA 19-9 in metastatic PDAC (p = 0.008 and p = 0.010) as an independent prognostic marker for overall survival.

Conclusion: IL-10 levels may have independent prognostic value in locally advanced PDAC, whereas CYFRA 21-1 levels are prognostic after PDAC surgery. CYFRA 21-1 and IL-8 have been identified to best discriminate metastatic from locally advanced patients.
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http://dx.doi.org/10.1007/s00432-022-04112-zDOI Listing
June 2022

Germline Polymorphisms in Genes Involved in the Antioxidant System Predict the Efficacy of Cetuximab in Metastatic Colorectal Cancer Patients Enrolled in FIRE-3 Trial.

Clin Colorectal Cancer 2022 May 23. Epub 2022 May 23.

Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address:

Background: Reactive oxygen species activate EGFR/RAS/MAPK signaling either through the inactivation of phosphatases or by direct oxidation of kinases. We hypothesized that functional single-nucleotide polymorphisms (SNPs) in antioxidant genes link to the efficacy of cetuximab in patients with metastatic colorectal cancer (mCRC).

Patients And Methods: We analyzed genomic and clinical data from FIRE-3, a phase III trial comparing cetuximab and bevacizumab along with FOLFIRI in untreated mCRC patients. Genomic DNA extracted from blood samples was genotyped. Thirteen functional SNPs in antioxidant genes were tested for associations with clinical outcomes.

Results: In total, 236 patients were included (FOLFIRI/cetuximab arm, n = 129; FOLFIRI/bevacizumab arm, n = 107). In univariate analysis, two SNPs (TXN2 rs4821494 and GPX4 rs4807542) were significantly associated with overall survival (OS) in the FOLFIRI/cetuximab arm. Multivariate analysis confirmed the significant association of TXN2 rs4821494 (T/T vs. any G allele, hazard ratio = 2.47, 95% confidence interval = 1.06-5.72, P = .03). In the FOLFIRI/bevacizumab arm, no SNPs were significantly associated with clinical outcomes. Treatment-by-SNP interaction test confirmed the predictive value of TXN2 rs4821494 (OS: P = .03).

Conclusion: TXN2 rs4821494 involved in the antioxidant system may predict the efficacy of cetuximab-based first-line chemotherapy in mCRC, warranting further validation studies.
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http://dx.doi.org/10.1016/j.clcc.2022.05.005DOI Listing
May 2022

Liquid Biopsy in Colorectal Cancer: Quo Vadis? Implementation of Liquid Biopsies in Routine Clinical Patient Care in Two German Comprehensive Cancer Centers.

Front Oncol 2022 12;12:870411. Epub 2022 May 12.

Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Objectives: The use of liquid biopsies (LB) in patients with solid malignancies enables comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) and has the potential to guide therapy stratification and support disease monitoring. To examine clinical uptake of LB in a real-world setting, LB implementation was analyzed at two German cancer centers (LMU Munich and Charité - Universitätsmedizin Berlin) between 2017 and 2021, with focus on colorectal cancer (CRC) patients.

Methods: In this retrospective analysis, all patients who received a LB between January 2017 and December 2021 as part of routine clinical management were included. To provide adequate context, we collected disease characteristics and technical specifications of the LB methods applied. Additionally, we examined the concordance of status in tumor tissue and LB. Finally, we discuss the potential of LB as a diagnostic tool to drive personalized treatment in CRC patients and how to implement LB in clinical routine.

Results: In total, our cohort included 86 CRC patients and 161 LB conducted in these patients between 2017 and 2021. In 59 patients, comparison between tissue-based and liquid-based molecular diagnostics, revealed a divergence in 23 (39%) of the evaluable samples.

Conclusion: Our real-world data analysis indicates that the possibilities of LB are not yet exploited in everyday clinical practice. Currently, the variety of methods and lack of standardization, as well as restricted reimbursement for liquid based CGP hinder the use of LB in clinical routine. To overcome these issues, prospective clinical trials are needed to provide evidence driving the implementation of LB into the management of CRC patients and to support their implementation into clinical guidelines.
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http://dx.doi.org/10.3389/fonc.2022.870411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134071PMC
May 2022

Efficacy of FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab in 1st-line treatment of older patients with RAS wild-type metastatic colorectal cancer: an analysis of the randomised trial FIRE-3.

Br J Cancer 2022 May 30. Epub 2022 May 30.

Department of Medicine III, LMU University Hospital Munich, München, Germany.

Background: The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients' age and sidedness of primary tumour.

Methods: The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (≥65 years) patients, followed by stratification according to primary tumour sidedness. ORR was compared using Fisher´s exact test, OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate Cox regression analyses assessed hazard ratios and 95% confidence intervals for OS and PFS.

Results: Overall, older patients with RAS WT tumours had a significantly shorter OS when compared to younger patients (25.9 months vs 29.3 months, HR 1.29; P = 0.02). Also the proportion of right-sided tumours was significantly greater in older patients (27.1% vs 17.9%; P = 0.029). Secondary resection rates were numerically higher in younger patients (25.4% vs. 17.6%, P = 0.068) than in older patients. This was primarily seen in the Cetuximab arm, where older patients underwent less likely resection (13.1% vs. 26%; P = 0.02). Older patients with left-sided tumours showed only a trend towards greater efficacy of cetuximab (HR 0.86; P = 0.38). In patients with right-sided primary tumours, older patients did not appear to benefit from cetuximab in contrast to younger patients (≥65 years: 16.6 months vs 23.6 months, HR 1.1; P = 0.87; <65 years: 21.9 months vs 16.4 months HR 1.5; P = 0.31).

Conclusions: In FIRE-3, OS was generally shorter in older patients in comparison to younger patients. This could be explained by the overrepresentation of right-sided tumours and a lower secondary resection rate in older patients. The efficacy of targeted therapy was dependent on tumour sidedness in older patients with RAS WT mCRC.

Clinical Trial: FIRE-3 (NCT00433927).
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http://dx.doi.org/10.1038/s41416-022-01854-yDOI Listing
May 2022

Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical Trials.

JNCI Cancer Spectr 2022 03;6(2)

Department of Medical Oncology, Institut Franco-Britannique, Levallois-Perret, France.

Background: We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials.

Methods: Associations between clinical and disease characteristics, time to initial progression, and rate of receipt of second-line therapy were evaluated. TTP and overall survival (OS) were compared between older and younger adults in first- and second-line trials by Cox regression, adjusting for age, sex, Eastern Cooperative Oncology Group Performance Status, number of metastatic sites and presence of metastasis in the lung, liver, or peritoneum. All statistical tests were 2-sided.

Results: Older adults comprised 16.4% of patients on first-line trials (870 total older adults aged >70 years; 4419 total younger adults aged ≤70 years, on first-line trials). Older adults and those with Eastern Cooperative Oncology Group Performance Status >0 were less likely to receive second-line therapy than younger adults. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariable analysis (odds ratio = 1.11, 95% confidence interval = 1.02 to 1.21, P = .01). Older and younger adults enrolled in second-line trials experienced similar median TTP and median OS (median TTP = 5.1 vs 5.2 months, respectively; median OS = 11.6 vs 12.4 months, respectively).

Conclusions: Older adults were less likely to receive second-line therapy for metastatic colorectal cancer, though we did not observe a statistical difference in survival outcomes vs younger adults following second-line therapy. Further study should examine factors affecting decisions to treat older adults with second-line therapy. Inclusion of geriatric assessment may provide better criteria regarding the risks and benefits of second-line therapy.
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http://dx.doi.org/10.1093/jncics/pkac014DOI Listing
March 2022

Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer.

JNCI Cancer Spectr 2022 May;6(3)

Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.

Adjuvant gemcitabine (aGC) is one standard of care after pancreatic ductal adenocarcinoma (PDAC) resection. No biomarker for its efficacy is established. As bacteria mediate gemcitabine resistance, we analyzed whether lipopolysaccharide (LPS) as surrogate for bacterial colonization is prognostic in PDAC patients treated with aGC or without aGC adjuvant gemcitabine. We detected LPS in 86 tumors from 376 patients, which defined a specific microbiome as revealed by 16 s-rRNA-sequencing. In the 230 aGC patients, LPS conferred worse disease-free survival (8.3 vs 13.7 months; hazard ratio = 1.75, 95% confidence interval = 1.22 to 2.49; log-rank P = .002) and overall survival (21.7 vs 28.5 months; hazard ratio = 1.80, 95% confidence interval = 1.23 to 2.57; log-rank P = .001) but not in the 146 naGC patients, which was confirmed in an independent validation cohort (n = 178). LPS may serve as a negative predictor for aGC efficacy in PDAC, which suggests a role for microbiome modification to overcome bacteria-mediated chemotherapy resistance.
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http://dx.doi.org/10.1093/jncics/pkac039DOI Listing
May 2022

[The views of cancer out-patients on the impact of the COVID-19 pandemic].

Dtsch Med Wochenschr 2022 Apr 11;147(10):41-49. Epub 2022 May 11.

Comprehensive Cancer Center München, Deutschland.

Background:  This study investigates current needs and psychosocial burden of out-patients with cancer during the COVID-19-Pandemic.

Material And Methods:  Between 11/2020 and 02/2021 122 cancer patients who underwent out-patient treatment at the Comprehensive Cancer Center Munich participated in the study. Based on a standardized, semi-structured interview, participants were asked about their knowledge and informational needs related to COVID-19, risk perception and concerns regarding continuing out-patient treatment, COVID-19 related distress, confidence in the national health system, and their readiness to get vaccinated against COVID-19. Additionally, patients filled out the distress thermometer (DT).

Results:  More than a third of the patients (34,2 %, n = 41/120) wanted to receive more information about the effects of the coronavirus on their cancer and their treatment. 17,2 % (n = 21/122) had faced changes concerning their current or planned treatment. 42/121 (34,7 %) of the patients were clinically distressed (DT ≥ 5). A possible overload of the health care system was the most commonly reported COVID-related concern (77,9 %, n = 95/122), followed by being concerned that their family members might be additionally worried about them (56,2 %, n = 68/121). 71,2 % (n = 74/104) of the patients are willing to be vaccinated; 60 % (n = 18/30) of those undecided or refusing at the time of the survey expressed a desire to have a consultation with an oncologist before giving their final consent to vaccination.

Discussion:  Corona-specific distress of cancer patients relates in particular to the course of therapy, but also to a possible overload of the health care system. Oncology care teams should allow space for questions from their patients, acknowledge possible uncertainties, provide emotional support, and draw attention to reliable sources of information.
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http://dx.doi.org/10.1055/a-1746-7534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095066PMC
April 2022

The impact of adjuvant therapy on outcome in UICC stage I pancreatic cancer.

Int J Cancer 2022 Apr 25. Epub 2022 Apr 25.

Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.

Adjuvant chemotherapy has become standard of care for pancreatic ductal adenocarcinoma (PDAC) as it improves patient outcome. However, its clinical meaning in early-stage, UICC I tumors remains uncertain. We examined the effect of adjuvant therapy on disease-free survival (DFS) and overall survival (OS) of UICC stage I PDAC patients treated at an academic tertiary care center between 2000 and 2016. Among 124 patients (69 male, 55 female; median age 68 years, range 41-84 years) with UICC stage I disease, adjuvant therapy improved both DFS (19.8 vs 12.8 months, HR 0.59, 95% CI: 0.37-0.94, P = .03) and OS (40.9 vs 20.3 months, HR 0.54, 95% CI: 0.35-0.84, P = .005). Multivariate analyses and propensity score matching confirmed the prognostic impact of adjuvant therapy independent of localization, differentiation and R-status. Thus, every patient with UICC I PDAC should receive adjuvant chemotherapy as it may improve outcome significantly. Our findings support the concept of PDAC as systemic disease from early stages on.
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http://dx.doi.org/10.1002/ijc.34044DOI Listing
April 2022

Should routine risk reduction procedures for the prevention and control of pandemics become a standard in all oncological outpatient clinics? The prospective COVID-19 cohort study: protect-CoV.

Med Oncol 2022 Apr 10;39(6):104. Epub 2022 Apr 10.

Comprehensive Cancer Center (CCC Munich LMU), Ludwig Maximilians University (LMU) Hospital, Munich, Germany.

Limited knowledge exists on the effectiveness of preventive preparedness plans for the care of outpatient cancer patients during epidemics or pandemics. To ensure adequate, timely and continuous clinical care for this highly vulnerable population, we propose the establishment of preventive standard safety protocols providing effective early phase identification of outbreaks at outpatient cancer facilities and communicating adapted standards of care. The prospective cohort study Protect-CoV conducted at the LMU Klinikum from mid-March to June 2020 investigated the effectiveness of a rapid, proactive and methodical response to protect patients and interrupt SARS-CoV-2 transmission chains during the first pandemic wave. The implemented measures reduced the risk of infection of individual cancer patients and ensured safe adjunctive infusion therapy in an outpatient setting during the early COVID-19 pandemic. In addition to the immediate implementation of standard hygiene procedures, our results underscore the importance of routine PCR testing for the identification of asymptomatic or pre-symptomatic COVID-19 cases and immediate tracing of positive cases and their contacts. While more prospective controlled studies are needed to confirm these results, our study illustrates the importance of including preventative testing and tracing measures in the standard risk reduction procedures at all out patient cancer centers.
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http://dx.doi.org/10.1007/s12032-022-01700-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994860PMC
April 2022

FIRE-9 - PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer.

BMC Cancer 2022 Apr 2;22(1):359. Epub 2022 Apr 2.

Department of Hematoogy, Oncology, and Cancer Immunology (CCM/CVK), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Background: Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer.

Methods: Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer-either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3-10 weeks before randomization-and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm.

Discussion: Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer.

Trial Registration: This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020-006,144-18).
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http://dx.doi.org/10.1186/s12885-022-09422-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976276PMC
April 2022

Response and Disease Dynamics in Untreated Metastatic Colorectal Cancer With Bevacizumab-Based Sequential vs. Combination Chemotherapy-Analysis of the Phase 3 XELAVIRI Trial.

Front Oncol 2022 18;12:751453. Epub 2022 Feb 18.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology, and Tumor Immunology Charité Virchow Klinikum (CVK), Berlin, Germany.

Introduction: Early tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial.

Methods: DpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex.

Results: In 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; < 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in / wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: < 0.001; OS: = 0.012) and molecular subgroup (PFS: < 0.001; OS: < 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: < 0.001, HR 0.532; OS: < 0.001, HR 0.574 vs. PFS: = 0.107; OS: = 0.965).

Conclusions: Initial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population.
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http://dx.doi.org/10.3389/fonc.2022.751453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895369PMC
February 2022

Strategies to successfully prevent COVID-19 outbreak in vulnerable uro-oncology patient population.

Infection 2022 Feb 24. Epub 2022 Feb 24.

Department of Urology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Purpose: As COVID-19 pandemic persists with variants, and despite effective vaccination campaigns, breakthrough infections surge. We implemented strategies to protect vulnerable patients of the uro-oncologic outpatient clinic. We adopted proactive non-symptomatic risk reduction measures, which include non-symptomatic testing requirements for both patients and health care professionals (HCP), intensified patient tracing and contact reduction by implementation of digital health options. Here, we present our best practice example to safely guide oncology professionals and patients with metastasized genitourinary cancers through the current and future pandemics.

Methods: Solely for this purpose, we created a registry of collected data (current telephone numbers, e-mail addresses, vaccination status). We collected a nasopharyngeal swab from every patient upon presentation for treatment. We implemented bi-weekly RNA-PCR assay tests for HCP with patient contact, and limited personal contact at our facility through digital patient consultations.

Results: We started implementing our COVID prevention model at the beginning of the second wave in September 2020 and included 128 patients with urologic malignancies requiring systemic treatment. After COVID vaccination became available in December 2020, all of our HCP were fully vaccinated within 6 weeks and 97% of our patients (125/128) within 9 months. We performed 1410 nasopharyngeal swabs during in-house visits, thereby detecting two COVID-19 infections among our patients, who both survived and successfully continued treatment. To further reduce personal contact, half of our consultations were fully operated digitally, with 76% (97/128) of our patients participating in our digital health offers.

Conclusion: The willingness of patients and HCPs to participate in the study allowed us to implement strict standards to prepare for the ongoing and future pandemics in outpatient cancer units. Next to general preventive measures such as frequent hand disinfection, wearing facial masks, and keeping distance, an important measure to protect vulnerable uro-oncology patients is the capability to perform virus genome sequencing to trace transmission chains.
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http://dx.doi.org/10.1007/s15010-022-01775-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867446PMC
February 2022

Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy.

Cancers (Basel) 2022 Jan 21;14(3). Epub 2022 Jan 21.

Department of Hematology, Oncology, and Tumorimmunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and HumboldtUniversität zu Berlin, 10117 Berlin, Germany.

Primary tumor sidedness (left vs. right) has prognostic and predictive impact on anti-EGFR agent efficacy and thus management of metastatic colorectal cancer (mCRC). This analysis evaluates the relevance of primary tumor location (PTL) in wild-type mCRC patients, when dividing the colorectal frame into six segments. This pooled analysis, performed on a single-patient basis of five randomized first-line therapy trials, evaluates the impact of exact PTL classification on baseline characteristics, prognosis and prediction of anti-EGFR antibody efficacy by chi-square and log-rank tests, the Kaplan-Meier method, Cox and logistic regressions. The PTL was significantly associated with metastatic spread: liver ( = 0.001), lung ( = 0.047), peritoneal ( < 0.001) and lymph nodes ( = 0.048). A multivariate analysis indicated an impact on anti-EGFR agent efficacy in terms of overall survival depending on the exact primary tumor location: from detrimental in caecal (HR 2.63), rather neutral effects in the ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99) and left flexure/descending colon (HR 0.91) to clear benefit in sigmoid (HR 0.71) and rectal (HR 0.58) primaries. Exact primary tumor location affects anti-EGFR antibody efficacy in a rather continuous than a dichotomous fashion in wild-type mCRC patients. This perspective might help to support clinical decisions when anti-EGFR antibodies are considered.
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http://dx.doi.org/10.3390/cancers14030526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833757PMC
January 2022

Comment on "Detection, Treatment, and Survival of Pancreatic Cancer Recurrence in the Netherlands: A Nationwide Analysis".

Ann Surg 2022 Feb 1. Epub 2022 Feb 1.

Department of Internal Medicine III, Ludwig-Maximilian-University, Munich, Germany German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany Department of Internal Medicine III, Ludwig-Maximilian-University, Munich, Germany German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany Department of General, Visceral and Transplantation Surgery, Ludwig-Maximilian-University, Munich, Germany.

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http://dx.doi.org/10.1097/SLA.0000000000005405DOI Listing
February 2022

Assessment of Metastatic Colorectal Cancer Patients' Preferences for Biologic Treatments in Germany Using a Discrete Choice Experiment.

Clin Colorectal Cancer 2022 06 20;21(2):122-131. Epub 2021 Dec 20.

HEOR, Amgen GmbH, Munich, Germany. Electronic address:

Background: Current treatment regimens for metastatic colorectal cancer (mCRC) include biologics such as epidermal growth factor receptor and vascular endothelial growth factor inhibitors, which have specific side-effect profiles. There is a lack of information on mCRC patient preference in Germany regarding biologics in combination with chemotherapy. This study aims to identify German mCRC patients' preference for these treatments PATIENTS AND METHODS: This was a multicenter cross-sectional discrete choice experiment (DCE). Data were collected using electronic case report forms and structured phone interviews. DCE attributes were related to efficacy, side effects, frequency of administration, and distance to treating physicians' practice. Patients' characteristics and choices were analyzed descriptively. Choice data was modeled using a random utility maximization framework.

Results: All attributes, except distance to treating physicians' practice, had a significant impact on patients' decision. The most important driver of patients' treatment decision was overall survival, followed by safety-related attributes and frequency of administration. Overall survival was the main driver in all subgroups analyzed. Risk of severe skin toxicities was more important to women, than men. In patients with prior experience of side effects, the risk of side effects accounted for 45% of a patient's decision, compared to 35% in those without prior experience.

Conclusion: Overall survival remains the most important driver in mCRC patients' preferences for biologic treatment in combination with chemotherapy. Attributes related to safety were less important to patients when considering their treatment decision. These results indicate that understanding patient preferences may lead to increased treatment compliance.
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http://dx.doi.org/10.1016/j.clcc.2021.12.002DOI Listing
June 2022

Novel systemic treatment approaches for metastatic pancreatic cancer.

Expert Opin Investig Drugs 2022 Mar 10;31(3):249-262. Epub 2022 Feb 10.

Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year overall survival rate of 10%, emphasizing the need for more effective therapies, especially in metastatic disease. The immunosuppressive tumor microenvironment, poor vascularization, and dense tumor stroma typical for PDAC are hurdles that need to be overcome by novel drugs. Investigations are moving toward more targeted treatments including immunotherapy and cell-based approaches.

Areas Covered: This article reviews emerging drugs in clinical development for metastatic PDAC, focusing on cellular therapies and novel treatments targeting metabolism, tumor stroma, oncogenic pathways and immunosuppression. With immunotherapy and CAR T-cell therapy on the rise in hematological malignancies, the transfer to solid tumors remains intriguing. Multiple exciting clinical trials investigating innovative therapeutic strategies for PDAC are currently ongoing and reviewed herein. ClinicalTrials.gov, conference abstracts and PubMed were searched in August 2021 and assessed for information on ongoing and published clinical studies.

Expert Opinion: With many challenges to overcome, the optimal therapy for patients with metastatic PDAC is likely to consist of a combination of different agents. We are slowly moving from entity-dependent approaches to ones more focused on molecular and pathological features. Increasingly personalized treatment plans tailored to each patient may be the future of PDAC therapy.
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http://dx.doi.org/10.1080/13543784.2022.2037552DOI Listing
March 2022

Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer ≥ 70 years.

Eur J Cancer 2022 03 13;163:1-15. Epub 2022 Jan 13.

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.

Purpose: Colorectal cancer (CRC) affects many older adults. We investigated the efficacy and safety of adding anti-epidermal growth factor receptor (EGFR) agents to doublet chemotherapy (DC) in older patients.

Methods: Patients with RAS wild-type (WT) metastatic CRC (mCRC) receiving first-line DC + anti-EGFR (n = 1191) or DC alone (n = 729) from seven trials in the Aide de Recherche en Cancerologie Digestive database were included. The prognostic and predictive effects of age were investigated. Progression-free and overall survival (OS) were evaluated between age groups (≥70 vs <70) for DC + anti-EGFR. In addition, outcomes were compared between DC+/-anti-EGFR within age groups in three trials with a DC alone arm. Subsequently, the same analysis was conducted for left-sided tumours. Adverse events grade ≥3 (G3+) were compared between age groups.

Results: Older (vs younger) patients receiving DC + anti-EGFR had similar progression-free survival (PFS) (8.7 vs 10.3 months; hazard ratio (HR) = 1.20 [0.96-1.49];p = 0.107) but inferior OS (21.3 vs 26.3; HR = 1.36 [1.08-1.72];p = 0.011). DC + anti-EGFR (vs DC alone) improved OS (23.9 vs 20.3; HR = 0.82 [0.70-0.95];p = 0.008) and PFS (11.2 vs 8.9; HR = 0.70 [0.60-0.82];p < 0.001) in younger but not older patients: OS (24.7 vs 17.6; HR [95% confidence interval {CI}] = 0.77 [0.58-1.04];p = 0.092) and PFS (9.1 vs 8.7; HR [95% CI] = 0.85[0.63-1.15];p = 0.287). In left-sided 'only' tumours, the following outcomes for older (vs younger) patients were observed. For DC + anti-EGFR, PFS 9 versus 11.2 months; HR1.10 (95% CI 0.83-1.46); p = 0.52, OS 25.6 vs 30.3 HR 1.32 (95% CI 0.97-1.79), p = 0.086. For DC + anti-EGFR (vs DC alone), PFS and OS for younger patients were 11.9 vs 9.2 months HR 0.60 (95% CI 0.47-0.78) p < 0.001 and 24.1 versus 23.3 months HR 0.84 (95% CI 0.67-1.04), respectively. For older patients, PFS and OS were 13.1 versus 8.5 months, HR 0.51 (95% CI, 0.28-0.93), P = 0.027 and 26.3 versus 16.5 months HR 0.49 (95% CI, 0.28-0.85), respectively. There was no significant difference in toxicity among different age groups.

Conclusions: Older (vs younger) patients with mCRC RAS WT patients had comparable toxicity and efficacy with the addition of anti-EGFR agents to chemotherapy.
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http://dx.doi.org/10.1016/j.ejca.2021.12.007DOI Listing
March 2022

Clonal hematopoiesis is associated with improved survival in patients with metastatic colorectal cancer from the FIRE-3 trial.

Blood 2022 03;139(10):1593-1597

Department of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

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http://dx.doi.org/10.1182/blood.2021014108DOI Listing
March 2022

Sotorasib for previously treated colorectal cancers with KRAS mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.

Lancet Oncol 2022 01 15;23(1):115-124. Epub 2021 Dec 15.

Queen Elizabeth Hospital and University of Adelaide, Woodville South, SA, Australia.

Background: Sotorasib, a specific, irreversible KRAS protein inhibitor, has shown monotherapy clinical activity in KRAS-mutated solid tumours, including colorectal cancer, in the CodeBreaK100 phase 1 trial. We aimed to investigate the activity and safety of sotorasib in phase 2 of the trial.

Methods: In this single-arm, phase 2 trial, adult patients with KRAS-mutated advanced solid tumours were enrolled, from 59 medical centres in 11 countries, if they were aged 18 years or older, had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, and had an Eastern Cooperative Oncology Group performance status of 1 or lower. Only data for patients with colorectal cancer, enrolled at 33 medical centres in nine countries, are presented from this basket trial. To be enrolled, the patients had to have progressed after receiving fluoropyrimidine, oxaliplatin, and irinotecan treatment. These patients were administered 960 mg sotorasib orally once per day until disease progression, development of unacceptable side-effects, withdrawal of consent, or death. The primary endpoint was objective response (complete or partial response) as assessed by blinded independent central review. Response was evaluated in patients who received at least one dose of sotorasib and had at least one measurable lesion at baseline; safety was evaluated in patients who received at least one dose of sotorasib. This analysis is a prespecified analysis triggered by the phase 2 colorectal cancer cohort. This study is registered with ClinicalTrials.gov, NCT03600883, and is active but no longer recruiting.

Findings: On March 1, 2021, at data cutoff, 62 patients with KRAS-mutant colorectal cancer had been enrolled between Aug 14, 2019, and May 21, 2020, and had received at least one dose of sotorasib monotherapy. Objective response was observed in six (9·7%, 95% CI 3·6-19·9) of 62 patients, all with partial response. Treatment-related adverse events at grade 3 occurred in six (10%) patients, the most common of which was diarrhoea (two [3%] of 62 patients), and at grade 4 occurred in one (2%) patient (blood creatine phosphokinase increase); no fatal events were recorded. Serious treatment-related adverse events occurred in two (3%) patients (back pain and acute kidney injury).

Interpretation: Although the 9·7% overall response rate did not reach the benchmark, oral administration of sotorasib once per day showed modest anti-tumour activity and manageable safety in these heavily pretreated chemorefractory patients. Sotorasib is under evaluation in combination with other therapeutics to increase potential activity and overcome potential resistance mechanisms.

Funding: Amgen.
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http://dx.doi.org/10.1016/S1470-2045(21)00605-7DOI Listing
January 2022

Distress in hospitalized cancer patients: Associations with personality traits, clinical and psychosocial characteristics.

Psychooncology 2022 05 11;31(5):770-778. Epub 2021 Dec 11.

Department of Psychosomatic Medicine and Psychotherapy, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.

Objective: To improve allocation of psychosocial care and to provide patient-oriented support offers, identification of determinants of elevated distress is needed. So far, there is a lack of evidence investigating the interplay between individual disposition and current clinical and psychosocial determinants of distress in the inpatient setting.

Methods: In this cross-sectional study, we investigated 879 inpatients with different cancer sites treated in a German Comprehensive Cancer Center. Assessment of determinants of elevated distress included sociodemographic, clinical and psychosocial characteristics as well as dimensions of personality. Multiple linear regression was applied to identify determinants of psychosocial distress.

Results: Mean age of the patients was M = 61.9 (SD = 11.8), 48.1% were women. In the multiple linear regression model younger age (β = -0.061, p = 0.033), higher neuroticism (β = 0.178, p = <0.001), having metastases (β = 0.091, p = 0.002), being in a worse physical condition (β = 0.380, p = <0.001), depressive symptoms (β = 0.270, p = <0.001), not feeling well informed about psychological support (β = 0.054, p = 0.046) and previous uptake of psychological treatment (β = 0.067, p = 0.020) showed significant associations with higher psychosocial distress. The adjusted R of the overall model was 0.464.

Conclusion: Controlling for sociodemographic characteristics and dispositional vulnerability, that is neuroticism, current clinical and psychosocial characteristics were still associated with hospitalized patients' psychosocial distress. Psycho-oncologists should address both, the more transient emotional responses, such as depressive symptoms, as well as more enduring patient characteristics, like neuroticism.
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http://dx.doi.org/10.1002/pon.5861DOI Listing
May 2022

Quantitative Imaging Biomarkers of the Whole Liver Tumor Burden Improve Survival Prediction in Metastatic Pancreatic Cancer.

Cancers (Basel) 2021 Nov 16;13(22). Epub 2021 Nov 16.

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany.

Finding prognostic biomarkers with high accuracy in patients with pancreatic cancer (PC) remains a challenging problem. To improve the prediction of survival and to investigate the relevance of quantitative imaging biomarkers (QIB) we combined QIB with established clinical parameters. In this retrospective study a total of 75 patients with metastatic PC and liver metastases were analyzed. Segmentations of whole liver tumor burden (WLTB) from baseline contrast-enhanced CT images were used to derive QIBs. The benefits of QIBs in multivariable Cox models were analyzed in comparison with two clinical prognostic models from the literature. To discriminate survival, the two clinical models had concordance indices of 0.61 and 0.62 in a statistical setting. Combined clinical and imaging-based models achieved concordance indices of 0.74 and 0.70 with WLTB volume, tumor burden score (TBS), and bilobar disease being the three WLTB parameters that were kept by backward elimination. These combined clinical and imaging-based models have significantly higher predictive performance in discriminating survival than the underlying clinical models alone ( < 0.003). Radiomics and geometric WLTB analysis of patients with metastatic PC with liver metastases enhances the modeling of survival compared with models based on clinical parameters alone.
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http://dx.doi.org/10.3390/cancers13225732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616514PMC
November 2021

Survival after secondary liver resection in metastatic colorectal cancer: Comparing data of three prospective randomized European trials (LICC, CELIM, FIRE-3).

Int J Cancer 2022 04 4;150(8):1341-1349. Epub 2021 Dec 4.

Medical Department, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.

Metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) have a chance of long-term survival and potential cure after hepatic metastasectomy. However, the appropriate postoperative treatment strategy is still controversial. The CELIM and FIRE-3 studies demonstrated that secondary hepatic resection significantly improved overall survival (OS). The objective of this analysis was to compare these favorable outcome data with recent results from the LICC trial investigating the antigen-specific cancer vaccine tecemotide (L-BLP25) as adjuvant therapy in mCRC patients with LLD after R0/R1 resection. Data from mCRC patients with LLD and secondary hepatic resection from each study were analyzed for efficacy outcomes based on patient characteristics, treatment and surveillance after surgery. In LICC, 40/121 (33%) patients, in CELIM 36/111 (32%) and in FIRE-3-LLD 29/133 (22%) patients were secondarily resected, respectively. Of those, 31 (77.5%) patients in LICC and all patients in CELIM were R0 resected. Median disease-free survival after resection was 8.9 months in LICC, 9.9 months in CELIM. Median OS in secondarily resected patients was 66.1 months in LICC, 53.9 months in CELIM and 56.2 months in FIRE-3-LLD. Median age was about 5 years less in LICC compared to CELIM and FIRE-3. Secondarily resected patients of LICC, CELIM and FIRE-3 showed an impressive median survival with a tendency for improved survival for patients in the LICC trial. A younger patient cohort but also more selective surgery, improved resection techniques, deep responses and a close surveillance program after surgery in the LICC trial may have had a positive impact on survival.
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http://dx.doi.org/10.1002/ijc.33881DOI Listing
April 2022

[Neoadjuvant and adjuvant therapy of resectable colon cancer - Current standards and developments].

Dtsch Med Wochenschr 2021 11 5;146(22):1457-1467. Epub 2021 Nov 5.

The present review focusses on perioperative diagnosis and treatment of resectable colon cancer. In UICC stages associated with a higher risk of recurrence, adjuvant chemotherapy after resection of the primary tumor is an established standard. While initial data also indicate the benefit of Neoadjuvant, pre-operative chemotherapy, a final evaluation is still pending. The main focus of molecular testing in the perioperative setting is the analysis of microsatellite instability, which should routinely be performed in defined subgroups. In UICC stage II without risk factors, adjuvant therapy has a limited benefit and therefore is not a preferred option. In UICC stage II with risk factors, adjuvant therapy can be performed. The approach here is based on the recommendations applicable to stage III. In UICC stage III with low risk, adjuvant chemotherapy with CAPOX for 3 months is preferentially recommended. In UICC stage III with high risk, adjuvant chemotherapy over 6 months is recommended, preferentially with FOLFOX. Microsatellite instability (MSI) is clearly associated with favorable prognosis in non-metastatic colon cancer. However, it cannot be considered a predictive factor for the efficacy of adjuvant chemotherapy. Specifically, recent data of the IDEA study have opened the arena for shared decision making between physicians and patients allowing to define individual treatment approaches based on common assessment of risks and benefits. After completion of perioperative treatment, structured follow-up is of great importance and should be carried out according to the recommendations of the S3 guideline.
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http://dx.doi.org/10.1055/a-1391-5124DOI Listing
November 2021

Pan-cancer Analysis of Homologous Recombination Repair-associated Gene Alterations and Genome-wide Loss-of-Heterozygosity Score.

Clin Cancer Res 2022 04;28(7):1412-1421

Vall d'Hebron Institute of Oncology (VHIO) and Vall d'Hebron University Hospital, Barcelona, Spain.

Purpose: To study associations across tumor types between genome-wide loss of heterozygosity (gLOH) and alterations in homologous recombination repair (HRR)-associated genes beyond BRCA1 and BRCA2.

Experimental Design: Genomic profiling using a targeted next-generation sequencing assay examining 324-465 genes (FoundationOne, FoundationOne Heme, and FoundationOne CDx; Foundation Medicine, Inc.) was performed in a cohort of 160,790 samples across different tumor types. Zygosity predictions and gLOH status were calculated and linked with alterations in 18 HRR-associated genes (BRCA1, BRCA2, PALB2, BARD1, ATR, ATRX, ATM, BAP1, RAD51B, RAD51C, RAD51D, BRIP1, NBN, CHEK1, CHEK2, FANCA, FANCC, MRE11) and other genomic features, using Fisher's exact test and Mann-Whitney U tests.

Results: We identified a strong correlation between elevated gLOH and biallelic alterations in a core set of HRR-associated genes beyond BRCA1 and BRCA2, such as BARD1, PALB2, FANCC, RAD51C, and RAD51D (particularly in breast, ovarian, pancreatic, and prostate cancer). Monoallelic/heterozygous alterations in HRR-associated genes were not associated with elevated gLOH. gLOH was also independently associated with TP53 loss. Co-occurrence of TP53 loss and alterations in HRR-associated genes, and combined loss of TP53-PTEN or TP53-RB1, was associated with a higher gLOH than each of the events separately.

Conclusions: Biallelic alterations in core HRR-associated genes are frequent, strongly associated with elevated gLOH, and enriched in breast, ovarian, pancreatic, and prostate cancer. This analysis could inform the design of the next generation of clinical trials examining DNA repair-targeting agents, including PARP inhibitors.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-2096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982267PMC
April 2022

Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212).

J Clin Oncol 2022 01 17;40(1):72-82. Epub 2021 Sep 17.

Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven, Wilhelmshaven, Germany.

Purpose: The randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with wild-type metastatic colorectal cancer.

Methods: Following first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival, objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher's exact test; odds ratios were indicated when appropriate. The trial is registered with ClinicalTrials.gov (NCT01991873).

Results: Overall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cutoff, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 months 5.7 months; HR, 0.72; 80% CI, 0.60 to 0.85; = .014). Overall survival (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 months 25.7 months; HR, 0.84; 95% CI, 0.60 to 1.18; = .32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (odds ratio, 1.96; 95% CI, 1.14 to 3.36; = .02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%).

Conclusion: In wild-type metastatic colorectal cancer, maintenance therapy with FU/FA plus Pmab induced a significantly superior PFS compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.
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http://dx.doi.org/10.1200/JCO.21.01332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683209PMC
January 2022
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