Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG).

Abstract

350 Background: The PD-1 inhibitor pembro has durable antitumor activity in pts with metastatic urothelial carcinoma. Upregulation of the PD-1 pathway has been observed in BCG-resistant NMIBC, suggesting pembro may benefit. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study; updated results for pts with carcinoma in situ (CIS) with or without papillary tumor (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary disease, who received adequate BCG therapy and were unable/unwilling to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts with HR NMIBC or progressive disease during treatment were required to discontinue. Primary end point: complete response rate (CRR); key secondary end points: duration of response and safety. Results: 103 pts (median age 73 years; CIS alone 71.8%; median number of prior BCG instillations 12) have enrolled in cohort A. 3-mo CRR rate was 38.8% (95% CI 29.4%-48.9%) by central assessment. Among 40 pts who achieved CR at 3 mo, 72.5% maintained CR at last follow-up (median 14.0 mo; range 4.0-26.3) and median CR duration has not been reached (range 0+ to 14.1+ mo). 80.2% of pts had a CR duration of ≥6 mo (Kaplan-Meier method). 10 (25.0%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle invasive or metastatic disease. Treatment-related adverse events (AEs) occurred in 65 (63.1%) pts; most frequent were pruritus (10.7%), fatigue (9.7%), diarrhea (8.7%), hypothyroidism (5.8%), and maculopapular rash (5.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.6%) pts; 1 death was considered treatment-related (colitis in patient inadequately treated with steroids). Immune-mediated AEs occurred in 19 (18.4%) pts. Conclusions: Pembro had encouraging activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial. Clinical trial information: NCT02625961.

Bacillus Calmette–Guérin‐unresponsive non‐muscle‐invasive bladder cancer: Its definition and future therapeutic strategies

“…The preliminary outcome of NCT02625961 with 103 patients (median age 73 years; CIS alone 71.8%) has been reported. 68 In the trial, the 3-month CR rate was 38.8%. Among 40 patients with CR at 3 months, 72.5% maintained CR, and stage progression was not observed (median follow-up period 14.0 months).…”

“…every 3 weeks for 24 months), respectively. The preliminary outcome of NCT02625961 with 103 patients (median age 73 years; CIS alone 71.8%) has been reported . In the trial, the 3‐month CR rate was 38.8%.…”

Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

“…One patient died as a result of treatment-related colitis. 77 Clinical data included in the package insert for 96 patients on this trial report a complete response rate of 41% (95% CI, 31%-51%) and a median duration of response (DOR) of 16.2 months with 46% of complete responses maintained for at least a year. 78…”

Immunotherapy for urothelial carcinoma: Metastatic disease and beyond

“…Histochemical studies observed that programmed cell death‐1 levels increase in BCG‐relapsing tumors and that PD‐L1 levels are associated with tumor stage progression, both of which suggest impaired T‐cell function. KEYNOTE‐057 is a single‐arm phase 2 study of pembrolizumab in patients with BCG‐unresponsive NMIBC . Among patients with carcinoma in situ with or without papillary disease (n = 103), the 3‐month CR rate was 38.8% (95% CI: 29.4‐48.9), within which 72.5% was maintained at the last 14.0‐month median follow‐up.…”