Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials
- PMID: 33975059
- DOI: 10.1016/j.ejca.2021.04.004
Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials
Abstract
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.
Keywords: Clinical outcomes; Clinical trial ineligible; IMDC; Immuno-oncology; Immunotherapy; Melanoma; Non–small-cell lung cancer; Real-world patients; Renal cell carcinoma; Trial eligibility.
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.L.G., I.S., D.E.M., Sh.D., H.A.I.G., Sa.D., B.W.E., S.G., M.S, A.P., D.M., L.A.W. and T.C. have no conflicts of interest to report. J.C.W. reports travel and accommodation expenses from Pfizer. J.M. is a member in the advisory board of Amgen, BMS, Merck, Novartis and Sanofi and reports research funding from Merck. N.S.B. reports honoraria and is a member in the advisory board of BMS, Merck, Pfizer, EMD Serono, Roche, Eisai, Ipsen and AstraZeneca. S.K.P. has a consulting or advisory role in Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol Myers Squibb, Astellas Pharma, Ipsen and Eisai and reports honoraria from Novartis, Medivation and Astellas Pharma and research funding from Medivation. E.D. reports research funding from Pfizer and Ipsen. T.K.C. has a consulting or advisory role in Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Prometheus Laboratories, Alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney cancer Association, Clinical Care options, PlatformQ Health, Navinata Health, Harborside Press, ASCO, The New England Journal of Medicine, Lancet Oncology, EMD Serono, HERON, Lilly and ESMO; acts as a leader in Dana-Farber Cancer Institute, NCCN, Kidney cancer Association, KidneyCAN and ASCO; has stock and other ownership interests in Pionyr and Tempest Therapeutics; reports honoraria from NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, Corvus Pharmaceuticals, Ipsen, Foundation Medicine, Eisai, PlatformQ Health, Clinical Care options, Navinata Health, Kidney cancer association, Exelixis, Prometheus, Lpath, The New England Journal of Medicine, Lancet Oncology, Cerulean Pharma, Alligent, EMD Serono, Heron and Lilly and reports research funding from Pfizer, Novartis, Merck, Exelixis, Tracon Pharma, GlaxoSmithKline, Bristol Myers Squibb, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, NCI, CDMRP/DOD and Gateway for Cancer Research. Medical writing and editorial assistance support may have been funded by communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies and Parexel. D.Y.C.H. has a consulting or advisory role in Pfizer, Novartis, Bristol Myers Squibb, Janssen, Astellas Pharma, Ipsen, Eisai and Merck and reports research funding from Pfizer, Novartis, Exelixis, Bristol Myers Squibb and Ipsen.
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