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Keynote-057 study: interim analysis


By Dr. Evanguelos Xylinas


The Keynote-057 a single-arm phase 2 study evaluated the efficacy and safety of pembrolizumab in pts with HR BCG-unresponsive NMIBC (NCT02625961). The updated follow-up of interim data and exploratory HRQoL analyses were reported at ESMO 2019.

The Keynote-057 study included patients with histologically confirmed HR BCG-unresponsive CIS with or without papillary tumors who received adequate BCG therapy and who were ineligible or refused radical cystectomy (cohort A) were eligible. Patients received pembrolizumab 200 mg Q3W for 24 mo or until disease recurrence, progression, or unacceptable toxicity; those who developed HR NMIBC or progressive disease were required to discontinue. Key end points: complete response rate (CRR), duration of response, and safety. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Bladder Cancer (FACT-Bl) scale.

Overall, 102 pts enrolled in cohort A as of enrollment cutoff. Median (range) duration of follow-up was 21.1 mo (4.6-33.4); CRR was 41.2% (95% CI, 31.5-51.4) by central assessment. Among 42 pts with CR, median CR duration was 13.5 mo (range, 0+ to 26.8+); 57.4% had CR ≥ 12 mo (Kaplan-Meier). 22 pts (52.4%) maintained CR at last follow-up. 20 (47.6%) experienced recurrent NMIBC after CR. At time of analysis, there were no occurrences of progression to muscle-invasive disease (T2) or metastatic bladder cancer. For pts with CR, HRQoL was stable over time. At a prespecified analysis timepoint of week 39, the majority of pts (71.1% for FACT-G total and 77.8% for FACT-G physical well-being score) had improved (≥7 or ≥ 3 point increase, respectively) or stable (change between –7 and +7 or –3 and +3 points, respectively) scores from baseline. Treatment-related adverse events (TRAEs) occurred in 67 (65.7%) pts; most frequent (≥10%) were fatigue (10.8%), pruritus (10.8%), and diarrhea (10.8%). Grade 3/4 TRAEs occurred in 13 (12.7%) pts.

Expert’s comment:

With an updated follow-up, Pembrolizumab continued to show encouraging antitumor activity in patients with HR BCG-unresponsive CIS with or without papillary tumors, while maintaining their quality of life. Moreover, the safety profile was consistent with the known profile of pembrolizumab. This study is of greatest importance evaluating this new bladder-sparing therapeutic option for patients in whom radical cystectomy is the only curative standard of care.


Read the abstract of the Keynote-057 study here.