2017 ASCO Annual Meeting!
Session: Genitourinary (Nonprostate) Cancer
Type: Oral Abstract Session
Time: Monday June 5, 8:00 AM to 11:00 AM
Location: Arie Crown Theater
Planned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC).
Genitourinary (Nonprostate) Cancer
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 4501)
Author(s): Dean F. Bajorin, Ronald De Wit, David J. Vaughn, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J. Vogelzang, Miguel Ángel Climent, Daniel Peter Petrylak, Toni K. Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stephane Culine, Cora N. Sternberg, Yabing Mai, Markus Puhlmann, Rodolfo F. Perini, Joaquim Bellmunt; Memorial Sloan Kettering Cancer Center, New York, NY; Erasmus MC Cancer Institute, Rotterdam, Netherlands; Abramson Cancer Center, Philadelphia, PA; CHU de Québec-Université Laval, Québec, QC, Canada; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; University of California, San Francisco, San Francisco, CA; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Fundación Instituto Valenciano de Oncología, Valencia, Spain; Smilow Cancer Hospital, New Haven, CT; Dana-Farber Cancer Institute, Boston, MA; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Radboud University Medical Center, Nijmegen, Netherlands; Westmead Hospital and Macquarie University, Sydney, Australia; University of Southern California Norris Comprehensive Cancer Center and Hospital, Los Angeles, CA; Hopital Saint-Louis, Paris, France; San Camillo Forlanini Hospital, Rome, Italy; Merck & Co., Inc., Kenilworth, NJ
Background: Second-line chemotherapies (chemo) for advanced UC have limited clinical benefit (OS, 7-9 mo). Data from the open-label, phase 3 KEYNOTE-045 study (NCT02256436) showed significantly longer OS with pembro v chemo (median, 10.3 v 7.4 mo; hazard ratio [HR], 0.73; P = 0.002) in recurrent, advanced UC. Data from a planned survival analysis are presented. Methods: Pts had histologically or cytologically confirmed UC, progression after platinum, ECOG PS 0-2, measurable disease (RECIST v1.1), and ≤2 lines of systemic therapy. Pts were randomly assigned 1:1 to pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Primary efficacy end points were OS and PFS (RECIST v1.1, blinded central review). ORR (RECIST v1.1, blinded central review) was a secondary end point. Results: 542 pts were enrolled (pembro, 270; chemo, 272). Baseline characteristics were generally similar between arms. As of Jan 18, 2017, median follow-up was 18.5 mo (range, 14.2-26.5). Median OS was significantly longer with pembro v chemo (10.3 v 7.4 mo; HR, 0.70; P< 0.001), and significance was maintained regardless of PD-L1 expression as measured by combined positive score (HR: CPS < 1%, 0.84; CPS ≥1%, 0.59; CPS < 10%, 0.76; CPS ≥10%, 0.57). OS benefit with pembro v chemo was seen regardless of age, ECOG PS, prior therapy, liver metastases, histology, and choice of chemo. The 18-mo OS rate (95% CI) was 36.1% (30.1%-42.0%) with pembro v 20.5% (15.2%-25.8%) with chemo (KM estimate). PFS was not different between arms. ORR was higher with pembro v chemo (21.1% v 11.0%), and median (range) duration of response was longer (not reached [1.6+-20.7+ mo] v 4.4 mo [1.4+-20.3]). 69% (pembro) v 36% (chemo) of responses lasted ≥12 mo. Fewer pts experienced a treatment-related AE with pembro v chemo (any grade, 61.3% v 90.2%; grade ≥3, 16.5% v 49.8%). Conclusions: The OS benefit and superior safety profile of pembro over chemo are maintained with longer follow-up. Combined, these results support the potential of pembro as a new standard of care for patients with UC who previously received platinum. Clinical trial information: NCT02256436