In this abstract, the authors focus instead on the health-related quality of life (HRQOL) outcomes in the KeyNote 045 study, with a specific emphasis on whether HRQOL impact was a marker for treatment efficacy. This was a prespecified secondary planned analysis at the time of study completion.
The EORTC QLQ-C30 HRQoL instrument was administered electronically at cycles 1–4, then every 2 cycles for up to 1 y and 30 d after discontinuation. The key HRQoL end points were 1) change from baseline to week 15 and 2) time to deterioration (TTD) (defined as ≥10-point decrease from baseline) in the QLQ-C30 global health status/QoL score. HRQoL was only assessed in patients (pts) who received ≥1 dose of assigned study treatment and completed ≥1 HRQoL instrument.
Of note, PD-L1 positive status was determined by a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more.
Of the 542 patients in the original study, 520 met inclusion criteria for the HRQoL evaluation – which is much higher than other similar assessments (see abstract 4526 summary). Baseline responses were similar between both arms and there was an 88% compliance rate for week 15 survey. Key finding from the study were:
1. From baseline to week 15, scores were stable for pembro (n = 266) but worsened for the 2nd-line chemo patients (n = 254)
a. The difference in means between arms was 9.05 (95% CI 4.61-13.48; P< 0.001)
2. At week 15, patients who were PD(-) status had improved scores with pembro but still had worsened scores with 2nd-line chemo (mean +5.97 vs –4.31), while pts with PD(+) status had less worsening with pembro (mean –3.54 vs –13.95) compared with 2nd line chemo)
3. On Kaplan-Meier analysis, time to deterioration (TTD) was prolonged with pembro (median 3.5 mo vs 2.2 mo, nominal 1-sided P = 0.002) compared to 2nd-line chemo
4. Rates of improvement (defined as ≥10-point increase from baseline) at week 15 were 31.2% with pembro and 22.0% with 2nd-line chemo; rates of deterioration were 28.9% and 40.6%, respectively
5. Importantly, patients in both arms who didn’t have progression of disease, had improvement from baseline (in the pembro arm) or at least less of a decrease (chemo arm).
Based on the original study results demonstrating OS benefit and these results demonstrating HRQoL superiority, the authors suggest that pembrolizumab should become a standard of care. Importantly, they had a high survey completion rate that strengthens their findings. Interestingly, PD-L1 positive patients did have a worsening of HRQoL, but less so than 2nd-line chemotherapy. While it would have been interesting to correlate HRQoL outcomes with clinical efficacy, the authors may have to consider this for future studies.
Presented By: Ronald De Wit, MD, PhD, Erasmus MC Cancer Institute, Rotterdam, Netherlands
Co-Author(s): Dean F. Bajorin, Joaquim Bellmunt, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J. Vogelzang, Miguel Ángel Climent, Daniel Peter Petrylak, Toni K. Choueiri, Andrea Necchi, Winald R. Gerritsen, Howard Gurney, David I. Quinn, Stephane Culine, Cora N. Sternberg, Yabing Mai, Haojie Li, Rodolfo F. Perini, David J. Vaughn
Institution(s): Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; 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; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; Westmead Hospital and Macquarie University, Sydney, Australia; University of Southern California Norris Comprehensive Cancer Center and Hospital, Los Angeles, CA; Hôpital Saint-Louis - AP-HP, Paris, France; San Camillo Forlanini Hospital, Rome, Italy; Merck & Co., Inc., Kenilworth, NJ; Abramson Cancer Center, Philadelphia, PA
Writted By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
1. Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF; KEYNOTE-045 Investigators. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017 Mar 16;376(11):1015-1026. doi: 10.1056/NEJMoa1613683. Epub 2017 Feb 17.
Clinical trial information: NCT02256436
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
Read the original abstract