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

Samuel A. Funt, Michael Lattanzi, Karissa Whiting, Hikmat Al-Ahmadie, Colleen Quinlan, Min Yuen Teo, Chung Han Lee, David Aggen, Danielle Zimmerman, Deaglan Mchugh, Arlyn Apollo, Trey D. Durdin, Hong Truong, Jeffrey Kamradt, Maged Khalil, Bradley Lash, Irina Ostrovnaya, Asia S. Mccoy, Grace Hettich, Ashley RegazziMarwah Jihad, Neha Ratna, Abigail Boswell, Kaitlyn Francese, Yuanquan Yang, Edmund Folefac, Harry W. Herr, S. Machele Donat, Eugene Pietzak, Eugene K. Cha, Timothy F. Donahue, Alvin C. Goh, William C. Huang, Dean F. Bajorin, Gopa Iyer, Bernard H. Bochner, Arjun V. Balar, Amir Mortazavi, Jonathan E. Rosenberg

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


PURPOSENeoadjuvant 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.METHODSEligible 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.RESULTSOf 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).CONCLUSIONNeoadjuvant 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.

Original languageEnglish (US)
Pages (from-to)1312-1322
Number of pages11
JournalJournal of Clinical Oncology
Issue number12
StatePublished - Apr 20 2022

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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