2829 - Health-Related Quality of Life (HRQoL) and Updated Follow-Up From KEYNOTE-057: Phase 2 Study of Pembrolizumab (pembro) for Patients (pts) With High-Risk (HR) Non–Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guérin (BCG)

Background

Efficacy and safety of pembro in pts with HR BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study (NCT02625961); updated follow-up of interim data and exploratory HRQoL analyses are reported.

Methods

Pts 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. Pts received pembro 200 mg Q3W for 24 mo or until 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.

Results

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.

Conclusions

Pembro continued to show encouraging antitumor activity in pts with HR BCG-unresponsive CIS with or without papillary tumors plus maintenance of HRQoL. The safety profile was consistent with the known profile of pembro.

Clinical trial identification

NCT02625961; December 9, 2015.

Editorial acknowledgement

Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

R. de Wit: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Janssen; Advisory / Consultancy: Clovis. G.S. Kulkarni: Advisory / Consultancy: Ferring; Advisory / Consultancy: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Theralase; Research grant / Funding (self): Biosyent; Honoraria (self), Travel / Accommodation / Expenses: AbbVie; Honoraria (self), Travel / Accommodation / Expenses: TerSera; Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Amgen. J.L. Boormans: Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Janssen; Research grant / Funding (self): GenomeDx Biosciences. L.E.M. Krieger: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas. E.A. Singer: Research grant / Funding (self): Astellas/Medivation. D.F. Bajorin: Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Genentech; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Urogen; Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Kamat: Research grant / Funding (institution): FKD; Honoraria (self), Research grant / Funding (institution): Merck; Research grant / Funding (institution): Telesta; Research grant / Funding (institution): Adolor; Honoraria (self): TMC Innovation; Honoraria (self): BMS; Honoraria (self): Arquer; Honoraria (self): MDxHealth; Honoraria (self): Photocure; Honoraria (self): Theralase; Honoraria (self): Cepheid; Honoraria (self): Medac; Honoraria (self): Asieris; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca. P. Grivas: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck & Co., Inc.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Educational unbranded activity: Genentech; Honoraria (self), Advisory / Consultancy: Dendreon; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Educational unbranded activity: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Exelixis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Biocept; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis Oncology; Honoraria (self), Advisory / Consultancy: EMD Serono; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self), Advisory / Consultancy: Driver Inc.; Honoraria (self), Advisory / Consultancy: QED Therapeutics; Honoraria (self), Advisory / Consultancy: Heron Therapeutics; Honoraria (self), Advisory / Consultancy: Janssen; Research grant / Funding (institution): Mirati; Research grant / Funding (institution): Oncogenex; Research grant / Funding (institution): Bavarian Nordic, Immunomedics. B.R. Konety: Advisory / Consultancy, Research grant / Funding (institution): Photocure; Advisory / Consultancy: Pacific Edge; Advisory / Consultancy: Taris; Advisory / Consultancy: Boston Scientific; Advisory / Consultancy: NxThera; Research grant / Funding (institution): Genomic Health; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS. T. Saretsky: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck and Co., Inc. H. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. K. Nam: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. E. Sbar: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: MSD; Shareholder / Stockholder / Stock options: BMS; Shareholder / Stockholder / Stock options: Pfizer. A.V. Balar: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Pfizer/EMD Serono. All other authors have declared no conflicts of interest.