2018 ASCO Annual Meeting!
Session: Compelling Combinations: Raising the Bar With Immunotherapy
Type: Clinical Science Symposium
Time: Sunday June 3, 9:45 AM to 11:15 AM
Location: Hall D1
Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC).
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 105)
Author(s): Luis G. Paz-Ares, Alexander Luft, Ali Tafreshi, Mahmut Gumus, Julien Mazieres, Barbara Hermes, Filiz Cay Senler, Andrea Fülöp, Jeronimo Rodriguez-Cid, Shunichi Sugawara, Ying Cheng, Silvia Novello, Balazs Halmos, Yue Shentu, Dariusz Kowalski; University Hospital 12 de October, Madrid, Spain; Leningrad Regional Clinical Hospital, St. Petersburg, Russia; Austin Health, Waterways, Australia; Kartal Research and Training Hospital, Istanbul, Turkey; Hôpital Larrey, Centre Hospitalier Universitaire Toulouse, Toulouse, France; Universitätskinikum Tübingen, Tuebingen, Germany; Ankara University Department of Medical Oncology, Ankara, Turkey; Országos Korányi TBC és Pulmonológiai Intézet, Budapest, Hungary, Budapest, Hungary; Oncology Center, Medica Sur Hospital, Mexico City, Mexico; Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan; Department of Oncology, Cancer Hospital of Jilin Province, Changchun, China; Department of Oncology, University of Turin, Orbassano, Italy; Albert Einstein College of Medicine, Bronx, NY; Merck & Co., Inc., Kenilworth, NJ; Maria Skłodowska-Curie Institute of Oncology, Warsaw, Poland
Background: Pembro plus pemetrexed and carboplatin resulted in superior objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) for untreated pts with non-sq NSCLC. Pembro is active in sq NSCLC, so combining with chemo is a rational next step. Methods: KEYNOTE-407 (NCT02775435) is a randomized, placebo-controlled, global study of 560 untreated pts with metastatic sq NSCLC with ECOG 0-1. Pts were stratified by type of taxane, PD-L1 (TPS <1% vs ≥1%), and site (East Asia vs other). Investigators chose taxane. Pts were randomized 1:1 to receive carboplatin 6 mg/mL/min and paclitaxel 200 mg/m2 every 3 weeks or nab-paclitaxel 100 mg/m2 weekly plus pembro or saline placebo for 4 cycles followed by pembro/placebo for a total of 35 treatments. Imaging is sent for blinded independent central review (BICR) per RECIST 1.1. The primary endpoints are PFS by BICR and OS in the intent-to-treat population. Alpha is strictly controlled at 0.025 one-sided; PFS and OS each have 0.01. A key secondary endpoint is ORR by BICR in about the first 200 pts randomized with 0.005 alpha. A second interim analysis will be performed on PFS and OS when approximately 332 PFS events will have occurred. The hazard ratio (target 0.7) will be estimated using a stratified Cox regression model. The arms will be compared with a stratified log-rank test. Enrollment completed at the end of 2017. Results: In the first interim analysis, the initial 204 pts were randomized 101 to pembro + chemo and 103 to chemo with median follow-up of 7.7 m (range 0.4, 13.9). Pts were 78% male, 48% < 65 y, and 28% ECOG PS 0. PD-L1 status was 35% TPS<1%. 32% used nab-paclitaxel. Per BICR pembro + chemo had an ORR of 58.4% compared to 35.0%, p-value 0.0004. Duration of response ≥6m was 65.8% for pembro + chemo and 45.6% for chemo by Kaplan-Meier estimates. Incidence grade ≥3 AEs was 64.4% for pembro + chemo and 74.5% for chemo. No new safety concerns were observed. Conclusions: Adding pembro almost doubled the ORR of chemo for pts with untreated metastatic sq NSCLC. Pembro + chemo has a tolerable safety profile. Results from a second interim analysis may be available prior to the meeting. Clinical trial information: NCT02775435