1747P - Impact of prior chemotherapy (Chemo) on pembrolizumab (Pembro) response in urothelial cancer (UC): Exploratory analysis of the phase III KEYNOTE-045 study

Background

KEYNOTE-045 (NCT02256436) demonstrated a survival benefit with pembro monotherapy vs chemo in pts with advanced UC whose disease progressed on platinum chemo. This post hoc exploratory analysis evaluated the impact of prior chemo on response to pembro monotherapy in KEYNOTE-045.

Methods

Pts with metastatic UC who progressed after platinum chemo were randomly assigned 1:1 to pembro 200 mg Q3W or investigator’s choice of paclitaxel, docetaxel, or vinflunine. OS and ORR with pembro were evaluated by best response to prior therapy before enrollment (investigator assessment) and by whether prior chemo was cisplatin- or non–cisplatin-based.

Results

Response to prior chemo was CR/PR in 73, SD in 65, and PD in 107 pts. Prior chemo was cisplatin-based in 180 and non–cisplatin-based in 90 pts. Median time from stopping prior chemo to start of pembro was 4.0 mo (range, 0.8-77.2) in all treated pts, and 6.3 mo (1.0-77.2), 4.5 mo (1.0-43.5), and 2.3 mo (0.8-52.2) in CR/PR, SD, and PD populations, respectively. OS appeared similar regardless of achieving CR/PR or SD to prior chemo or if last line of prior chemo was cisplatin- or non–cisplatin-based (Table). ORR to pembro by best response to prior chemo was 24.7% (95% CI, 15.3-36.1) for CR/PR, 18.5% (95% CI, 9.9-30.0) for SD, and 19.6% (95% CI, 12.6-28.4) for PD. ORR to pembro by last prior chemo was 25.6% (95% CI, 19.4-32.6) for cisplatin-based and 14.4% (95% CI, 7.9-23.4) for non–cisplatin-based therapy. Table: 1747P

^amedian time from initiation of last prior treatment to death^blast prior chemotherapy

Conclusions

In this post hoc exploratory analysis, response to pembro monotherapy occurred regardless of prior response to chemo. While pts with PD as best response to chemo had numerically lower survival, pts still responded and benefited from pembro treatment. Limitations included that the responses based on investigator assessment of the prior chemo response were not reconciled by the Sponsor using imaging data and the small sample size.

Clinical trial identification

NCT02256436, Release date: October 3, 2014.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Mallory Campbell, PhD and Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

R. De Wit: Financial Interests, Personal and Institutional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Sanofi, Bayer, Bayer; Financial Interests, Personal, Advisory Board: Merck, Orion, Astellas; Financial Interests, Personal, Invited Speaker: Astellas. Y. Fradet: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Ferring, Merck, Janssen, Sanofi, TerSera, IMV Inc.; Financial Interests, Institutional, Research Grant: Merck, TerSera; Financial Interests, Institutional, Advisory Board: IMV Inc.; Other, Institutional, Advisory Board: IMV Inc.; Financial Interests, Personal, Other, Travel expenses: Sanofi, TerSera. L. Fong: Financial Interests, Institutional, Research Grant: AbbVie, Merck, Roche/Genentech, Amgen, BMS. N.J. Vogelzang: Financial Interests, Personal, Advisory Role: Pfizer, Bayer, Genentech/Roche, AstraZeneca, Caris Life Sciences, Tolero Pharmaceuticals, Merck, Astellas Pharma, Boehringer Ingelheim, Corvus Pharmaceuticals, Modra Pharmaceuticals, Clovis Oncology, Janssen Oncology, Eisai, Myovant Sciences; Financial Interests, Personal, Full or part-time Employment: US Oncology; Financial Interests, Personal, Speaker’s Bureau: Bayer, Sanofi, Genentech/Roche, Bristol Myers Squibb, Seattle Genetics/Astellas, Clovis Oncology, AVEO, Myovant Sciences, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genentech/Roche, US Oncology, Pfizer, Bayer/Onyx, Exelixis, AstraZeneca/MedImmune, Sanofi/Aventis; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Stocks/Shares: Caris Life Sciences; Financial Interests, Personal, Other, Honoraria: UpToDate, Pfizer, Novartis, Merck; Financial Interests, Institutional, Research Grant: US Oncology, Endocyte, Merck, Suzhou Kintor Pharmaceuticals. 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