Neoadjuvant Atezolizumab Plus Gemcitabine and Cisplatin in Muscle-Invasive Bladder Cancer

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In a phase II trial reported in the Journal of Clinical Oncology, Funt et al found that the combination of neoadjuvant atezolizumab with gemcitabine and cisplatin resulted in a high rate of tumor downstaging to < pT2N0 in patients with muscle-invasive bladder cancer.

Study Details

The U.S. multicenter trial included 39 evaluable patients with muscle-invasive bladder cancer (cT2–T4aN0M0) enrolled between February 2018 and May 2020. Patients received a lead-in dose of atezolizumab followed at 2 weeks by four cycles of gemcitabine/cisplatin plus atezolizumab every 21 days and another dose of atezolizumab 3 weeks later, prior to radical cystectomy and pelvic lymph node dissection.

Atezolizumab was given at 1,200 mg, gemcitabine at 1,000 mg/m2 once on days 1 and 8, and cisplatin at either 70 mg/m2 once on day 1 or as a split dose at 35 mg/m2 once on days 1 and 8. The primary endpoint was non–muscle-invasive downstaging to < pT2N0; the combination was to be considered promising if downstaging occurred in 19 or more of the 39 evaluable patients.


At radical cystectomy and pelvic lymph node dissection, downstaging to < pT2N0 was achieved in 27 (69%, 95% confidence interval [CI] = 55%–79%) of 39 patients, including pathologic complete response (pT0N0) in 16 (41%). Among the remaining 12 patients: 2 (5%) had pT2N0 disease and 7 (18%) were nonresponders with node-positive disease; 2 patients (5%) developed metastatic disease prior to cystectomy and lymph node dissection and were considered nonresponders; and 1 patient refused cystectomy and received radiotherapy to the bladder with concurrent gemcitabine. The latter patient was considered a nonresponder but had not exhibited relapse over 36-month follow-up from the start of study therapy. Over a median follow-up of 16.5 months (range = 7.0–33.7 months), relapse was observed in none of the patients with < pT2N0 and in 4 (11%) with ≥ pT2N0.


  • Neoadjuvant atezolizumab plus gemcitabine/cisplatin achieved downstaging to < pT2N0 in 69% of patients.
  • No relapses were observed in patients achieving < pT2N0.

PD-L1–positive status was defined as expression on ≥ 5% of tumor-infiltrating immune cells. Among four PD-L1–positive patients, all achieved < pT2N0. Among 34 with PD-L1 expression of < 5%, 23 (68%) achieved < pT2N0 and 11 (32%) were ≥ pT2N0 (P = .3 for association between PD-L1 and < pT2N0).

At a median follow-up of 23.6 months (range = 12.0–38.2 months), median relapse-free survival and median overall survival were not reached. Patients who achieved < pT2N0 had significantly better relapse-free survival vs those with ≥ pT2N0 (P < .001).

Adverse Events

The most common treatment-related adverse events of any grade in 44 patients evaluated for safety were neutropenia (59%), fatigue (55%), anemia (55%), and nausea (50%). Grade 3 or 4 treatment-related adverse events occurred in 59% of patients, most commonly neutropenia (36%, no febrile neutropenia) and lymphopenia (16%). Grade 3 immune-related adverse events occurred in five patients (11%), with two requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range = 5.1–17 weeks); no patients failed to undergo radical cystectomy due to adverse events.  

The investigators concluded, “Neoadjuvant gemcitabine/cisplatin plus atezolizumab is a promising regimen for muscle-invasive bladder cancer 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.”

Samuel A. Funt, MD, of the Division of Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and by Genentech/Roche. For full disclosures of the study authors, visit

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