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.
| Original language | English |
|---|---|
| Article number | 100152 |
| Journal | ESMO Open |
| Volume | 6 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 06.2021 |
Funding
The authors thank the patients participating in the trial and their families, the investigators, and F. H. R. for providing the clinical trial data from the SAUL study. Editorial support was provided by Katrin Gudmundsdottir, PhD (KG Medical Writing Ltd) funded by the Hellenic Genito-Urinary Cancer Group (HGUCG). The authors thank the patients participating in the trial and their families, the investigators, and F. H. R. for providing the clinical trial data from the SAUL study. Editorial support was provided by Katrin Gudmundsdottir, PhD (KG Medical Writing Ltd) funded by the Hellenic Genito-Urinary Cancer Group (HGUCG). This work (sub-analysis of the SAUL trial) was supported by the Hellenic Genito-Urinary Cancer Group (HGUCG) (no grant number). The sponsor (F. Hoffmann-La Roche) played a role in the design and conduct of the original study and in the collection, management, analysis and interpretation of the original study data. HGUCG provided support in the preparation of this manuscript but had no involvement in the design of the study or the collection, management, analysis and interpretation of the data. The SAUL trial was sponsored and funded by F. Hoffmann-La Roche, Basel, Switzerland (no grant number). 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. The data are available from the corresponding author upon reasonable request. This work (sub-analysis of the SAUL trial) was supported by the Hellenic Genito-Urinary Cancer Group (HGUCG) (no grant number). The sponsor (F. Hoffmann-La Roche) played a role in the design and conduct of the original study and in the collection, management, analysis and interpretation of the original study data. HGUCG provided support in the preparation of this manuscript but had no involvement in the design of the study or the collection, management, analysis and interpretation of the data. The SAUL trial was sponsored and funded by F. Hoffmann-La Roche, Basel, Switzerland (no grant number).
Research Areas and Centers
- Research Area: Luebeck Integrated Oncology Network (LION)
DFG Research Classification Scheme
- 2.22-14 Hematology, Oncology
- 2.22-23 Reproductive Medicine, Urology
