Title

Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial.

Authors

Samuel A Funt, Memorial Sloan Kettering Cancer Center
Michael Lattanzi, Memorial Sloan Kettering Cancer Center
Karissa Whiting, Memorial Sloan Kettering Cancer Center
Hikmat Al-Ahmadie, Memorial Sloan Kettering Cancer Center
Colleen Quinlan, Memorial Sloan Kettering Cancer Center
Min Yuen Teo, Memorial Sloan Kettering Cancer Center
Chung-Han Lee, Memorial Sloan Kettering Cancer Center
David Aggen, Memorial Sloan Kettering Cancer Center
Danielle Zimmerman, Memorial Sloan Kettering Cancer Center
Deaglan McHugh, Memorial Sloan Kettering Cancer Center
Arlyn Apollo, Memorial Sloan Kettering Cancer Center
Trey D Durdin, Memorial Sloan Kettering Cancer Center
Hong Truong, Memorial Sloan Kettering Cancer Center
Jeffrey Kamradt, Memorial Sloan Kettering Cancer Center
Maged Khalil MD, Lehigh Valley Health NetworkFollow
Bradley Lash, Lehigh Valley Health NetworkFollow
Irina Ostrovnaya, Memorial Sloan Kettering Cancer Center
Asia S McCoy, Memorial Sloan Kettering Cancer Center
Grace Hettich, Memorial Sloan Kettering Cancer Center
Ashley Regazzi, Memorial Sloan Kettering Cancer Center
Marwah Jihad, Memorial Sloan Kettering Cancer Center
Neha Ratna, Memorial Sloan Kettering Cancer Center
Abigail Boswell, Memorial Sloan Kettering Cancer Center
Kaitlyn Francese, New York University Langone Medical Center
Yuanquan Yang, Ohio State University Wexner Medical Center
Edmund Folefac, Ohio State University Wexner Medical Center
Harry W Herr, Memorial Sloan Kettering Cancer Center
S Machele Donat, Memorial Sloan Kettering Cancer Center
Eugene Pietzak, Memorial Sloan Kettering Cancer Center
Eugene K Cha, Memorial Sloan Kettering Cancer Center
Timothy F Donahue, Memorial Sloan Kettering Cancer Center
Alvin C Goh, Memorial Sloan Kettering Cancer Center
William C Huang, Memorial Sloan Kettering Cancer Center
Dean F Bajorin, Memorial Sloan Kettering Cancer Center
Gopa Iyer, Memorial Sloan Kettering Cancer Center
Bernard H Bochner, Memorial Sloan Kettering Cancer Center
Arjun V Balar, Memorial Sloan Kettering Cancer Center
Amir Mortazavi, Memorial Sloan Kettering Cancer Center
Jonathan E Rosenberg, Memorial Sloan Kettering Cancer Center

Publication/Presentation Date

1-28-2022

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 (

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.

First Page

2101485

Last Page

2101485

ISSN

1527-7755

Disciplines

Oncology

PubMedID

35089812

Department(s)

Hematology-Medical Oncology Division

Document Type

Article

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