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)

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/m2Q3W, docetaxel 75 mg/m2Q3W, or vinflunine 320 mg/m2Q3W. 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 followup. Combined, these results support the potential of pembro as a new standard of care for patients with UC who previously received platinum.