SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy
A Bamias, A S Merseburger, Y Loriot, N James, E Choy, D Castellano, F Lopez-Rios, F Calabrò, M Kramer, G de Velasco, R Zakopoulou, K Tzannis, C N Sternberg, A Bamias, A S Merseburger, Y Loriot, N James, E Choy, D Castellano, F Lopez-Rios, F Calabrò, M Kramer, G de Velasco, R Zakopoulou, K Tzannis, C N Sternberg
Abstract
Background: The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC.
Patients and methods: This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test.
Results: Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P < 0.001); median OS (mOS) for 0, 1 and 2-3 risk factors was 17.9, 8.9 and 3.3 months, respectively. Significant associations were also observed between OS and TFLC (P < 0.001), programmed death-ligand 1 (PD-L1) expression (P = 0.002), and prior perioperative chemotherapy (P = 0.013); mOS was 6.97 versus 11.63 months for TFLC ≤6 versus >6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes.
Conclusions: Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC.
Keywords: PD-L1; bladder cancer; immunotherapy; platinum; prognostic factors; urothelial carcinoma.
Conflict of interest statement
Disclosure AB: honoraria, advisory and research funding from Roche, BMS, MSD, Ipsen, Debiopharm, Basilea, Pierre Fabre and Janssen; and steering committee member for Roche. ASM: lectures/speaker honoraria from AstraZeneca, Bristol-Myers Squibb, Eisai, Ipsen, MSD, Merck Serono, Janssen, Takeda, TEVA, Astellas, Novartis, Pfizer and Roche; consultant for AstraZeneca, Astellas, Bristol-Myers Squibb, Ipsen, Janssen, EUSA Pharma, MSD, Merck Serono, Novartis, Takeda, Teva, Pfizer and Roche; research and clinical trials support from AstraZeneca, Astellas, Bristol-Myers Squibb, Ipsen, Janssen, EUSA Pharma, MSD, Merck Serono, Novartis, Takeda, Teva, Pfizer and Roche. YL: personal fees from Roche, Janssen, Astellas, MSD, Pfizer, Roche, BMS, Immunomedics, AstraZeneca, Sanofi and Seattle Genetics; grants from Janssen, MSD and Sanofi; non-financial support from Janssen, Roche, AstraZeneca and Sanofi. NJ: consultancy from Merck, Roche and AstraZeneca; trial funding (to institution) from Merck, Roche and AstraZeneca. EC: research grants from Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Sanofi and UCB; consultancy from AbbVie, Amgen, Biogen, Biocon, Chugai Pharma, Eli Lilly, Gilead, Janssen, Merck Serono, Novartis, Pfizer, Regeneron, Roche, R-Pharm and Sanofi; and speakers fees from AbbVie, Amgen, Bristol Myer Squibb, Chugai Pharma, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB. DC: personal fees for advisory boards/speaker engagements from Roche, Janssen, Astellas, MSD, Ipsen, Pfizer, Bristol-Myers Squibb, Bayer, AstraZeneca, Novartis, Lilly, Sanofi, Pierre Fabre and Boehringer Ingelheim. FL-R: honoraria from AstraZeneca, Bayer, BMS, Lilly, MSD, Pfizer, Roche and Thermo Fisher; and research funding from Lilly, Roche and Thermo Fisher. FC: advisory role for BMS, MSD, Pfizer and AstraZeneca. MK: honoraria/consultation for Bayer, BMS, EUSAI, Novartis, Merck, MSD, Pfizer and Roche; travel grants from Ipsen, Janssen, Merck and Novartis. GdeV: support for clinical trials and scientific projects for Pfizer, Roche and Ipsen; and speaker fees and consulting for Pfizer, Novartis, Roche, MSD, Astellas, Bayer, Ipsen, Janssen, Merck, EUSA Pharma and BMS. CNS: consultant for Pfizer, MSD, Merck, AstraZeneca, Astellas, Sanofi-Genzyme, Roche-Genentech, Incyte, BMS, Foundation Medicine, Immunomedics (now Gilead), Medscape, UroToday, CCO Clinical, Janssen and NCI. All other authors have declared no conflicts of interest.
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Source: PubMed