ASCO GU 2018: Two-year Follow-up: 3 KEYNOTE-045 Trial of Pembrolizumab vs Investigator’s Choice Chemotherapy in Recurrent, Advanced Urothelial Cancer

San Francisco, CA ( Based on interim results from the phase 3 KEYNOTE-045 study comparing pembrolizumab (pembro) vs. investigator’s choice (paclitaxel, docetaxel, or vinflunine) or chemotherapy (chemo), pembro was approved for the treatment of locally advanced or metastatic UC that has progressed during or after a platinum-containing regimen. The authors presented updated results after 2 years of follow-up.

Eligible patients had histologically or cytologically confirmed UC, with progression after platinum, and ECOG PS 0-2,  with measurable disease according to the RECIST v1.1, and a history of  ≤2 lines of systemic therapy. Patients 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 overall survival (OS) and progression free survival (PFS). Objective response rate (ORR) was a secondary end point.

Among the 542 enrolled patients (pembro, 270; chemo, 272), median follow-up was 27.7 mo. Median OS was significantly longer with pembro vs. chemo (10.3 v 7.3 mo; HR, 0.70; P< 0.0002). OS benefit with pembro vs. chemo was seen in all PD-L1 expression subgroups (HR: combined positive score [CPS] < 1, 0.82; CPS ≥1, 0.58; CPS < 10, 0.75; CPS ≥10, 0.56) and was maintained regardless of age, ECOG PS, prior therapy, liver metastases, baseline hemoglobin, time from last chemo, histology, risk factor group, and choice of chemo. PFS was not different between arms (2.1 v 3.3 mo; HR, 0.96; P = 0.32). ORR was higher with pembro vs. chemo (21.1% v 11.0%). Median duration of response was longer with pembro (not reached) vs. 4.4 months in chemo, and a greater proportion of responses lasted ≥12 mo (68% v 35%) as assessed by Kaplan-Meier method. Fewer patients with pembro vs. chemo experienced a treatment-related adverse event of any grade (62.0% v 90.6%) and a grade ≥3 adverse event (16.5% v 50.2%).

Results observed over 2 years of follow-up, including OS benefit and superior safety with pembro vs. chemo, were consistent with the interim analyses that led to the approval of pembro in locally advanced or metastatic UC that progressed during or after platinum-based chemotherapy. Clinical trial information: NCT02256436

Presented by: Joaquim Bellmunt, MD, PhD Dana-Farber Cancer Institute, Boston, MA, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA