Neoadjuvant atezolizumab with gemcitabine and cisplatin in patients with muscle-invasive bladder cancer: A multicenter, single-arm, phase II trial Journal Article
| Authors: | Funt, S. A.; Lattanzi, M.; Whiting, K.; Al-Ahmadie, H.; Quinlan, C.; Teo, M. Y.; Lee, C. H.; Aggen, D.; Zimmerman, D.; McHugh, D.; Apollo, A.; Durdin, T. D.; Truong, H.; Kamradt, J.; Khalil, M.; Lash, B.; Ostrovnaya, I.; McCoy, A. S.; Hettich, G.; Regazzi, A.; Jihad, M.; Ratna, N.; Boswell, A.; Francese, K.; Yang, Y.; Folefac, E.; Herr, H. W.; Donat, S. M.; Pietzak, E.; Cha, E. K.; Donahue, T. F.; Goh, A. C.; Huang, W. C.; Bajorin, D. F.; Iyer, G.; Bochner, B. H.; Balar, A. V.; Mortazavi, A.; Rosenberg, J. E. |
| Article Title: | Neoadjuvant atezolizumab with gemcitabine and cisplatin in patients with muscle-invasive bladder cancer: A multicenter, single-arm, phase II trial |
| Abstract: | PURPOSE: Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC. METHODS: Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non-muscle-invasive downstaging to < pT2N0. RESULTS: Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) < pT2N0, including 16 (41%) pT0N0. No patient with < pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)-positive tumors and were all < pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved < pT2N0 and 11 of 34 (32%) were ≥ pT2N0 (P = .3 for association between PD-L1 and < pT2N0). CONCLUSION: Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with < pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker. |
| Keywords: | clinical trial; cisplatin; gemcitabine; neoadjuvant therapy; antineoplastic agent; phase 2 clinical trial; neoplasm recurrence, local; antineoplastic combined chemotherapy protocols; pathology; bladder tumor; urinary bladder neoplasms; monoclonal antibody; multicenter study; tumor recurrence; cystectomy; neoplasm invasiveness; deoxycytidine; muscle; muscles; programmed death 1 ligand 1; adverse event; tumor invasion; antibodies, monoclonal, humanized; humans; human; male; female; atezolizumab; b7-h1 antigen; doxecitine |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 40 |
| Issue: | 12 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2022-04-20 |
| Start Page: | 1312 |
| End Page: | 1322 |
| Language: | English |
| DOI: | 10.1200/jco.21.01485 |
| PUBMED: | 35089812 |
| PROVIDER: | scopus |
| PMCID: | PMC9797229 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
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