The use of a checkpoint inhibitor combined with chemotherapy in the neoadjuvant setting appeared to be effective for patients with muscle-invasive bladder cancer (MIBC), according to results from a phase II trial.

Among 39 patients, the addition of the PD-L1 inhibitor atezolizumab (Tecentriq) to gemcitabine and cisplatin resulted in a non-muscle-invasive downstaging rate of 69% and a complete response rate of 41%, reported Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues.

Median follow-up from start of treatment was 23.6 months, with median relapse-free survival and overall survival not reached.

Of the patients with <pT2N0 disease, none relapsed; four patients with ≥pT2N0 relapsed over a median follow-up of 16.5 months, the authors noted in the Journal of Clinical Oncology.

The response rates in this study compared favorably to those reported for gemcitabine/cisplatin, as well as dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin, which are the neoadjuvant regimens preferred by the National Comprehensive Cancer Network, they pointed out.

Rosenberg also participated in a trial evaluating the safety and efficacy of adding pembrolizumab (Keytruda) to trimodal bladder preservation therapy for MIBC.

In that trial, the first 54 patients treated with pembrolizumab followed by maximal transurethral resection of the bladder tumor and concurrent chemotherapy and radiation had an estimated 1-year bladder-intact disease-free survival rate of 89%, according to preliminary results reported at last year’s American Society of Clinical Oncology virtual meeting.

The results from that trial and the current study “show that there is promise in this approach as part of a multimodality treatment paradigm, and further trials are warranted,” Rosenberg told MedPage Today.

“Biomarker work from these studies continues to progress, and these data may inform patient selection for the next generation of trials,” he added. “While the data for chemoimmunotherapy in the metastatic setting has been disappointing to date, the data in the neoadjuvant setting when combined with gemcitabine/cisplatin suggest the combinations may be highly active.”

In this multicenter single-arm trial, 39 patients with MIBC (84.6% men, median age 65) received a dose of atezolizumab followed 2 weeks later by gemcitabine and cisplatin every 21 days for four cycles with atezolizumab on day 8, and then another dose of atezolizumab 3 weeks after completion of chemotherapy, before undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND). The primary outcome of the trial was non-muscle-invasive downstaging to <pT2N0.

Four of the 39 patients had PD-L1-positive tumors and were all <pT2N0. Of the patients with PD-L1-low or -negative tumors, 23 of 34 achieved <pT2N0, and 11 were ≥pT2N0 (P=0.3 for association between PD-L1 and <pT2N0).

Two patients exhibited pT2N0 disease at RC-PLND, and seven nonresponders had node-positive disease at RC-PLND. Two patients developed metastatic disease prior to RC-PLND and were considered nonresponders.

The most common treatment-related adverse events (TRAEs) of any grade were neutropenia (59%), fatigue (55%), anemia (55%), and nausea (50%). A total of 26 patients experienced a grade ≥3 TRAE, the most common of which was grade 3/4 neutropenia (36%). No patients experienced AE-related delays to radical cystectomy and pelvic lymph node dissection.

Rosenberg and colleagues noted that there are ongoing phase III trials evaluating gemcitabine/cisplatin versus gemcitabine/cisplatin combined with pembrolizumab, nivolumab (Opdivo) with or without the indoleamine 2,3-dioxygenase inhibitor linrodostat, and durvalumab (Imfinzi).

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