2018 ASCO Annual Meeting!
Session: Plenary Session Including the Science of Oncology Award and Lecture
Type: Plenary Session
Time: Sunday June 3, 1:00 PM to 4:00 PM
Location: Hall B1
Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr LBA4)
Author(s): Gilberto Lopes, Yi-Long Wu, Iveta Kudaba, Dariusz Kowalski, Byoung Chul Cho, Gilberto Castro, Vichien Srimuninnimit, Igor Bondarenko, Kaoru Kubota, Gregory M. Lubiniecki, Jin Zhang, Debra A. Kush, Tony Mok; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL; Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China; Riga East Clinical University - Latvian Oncology Center, Riga, Latvia; The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warszawa, Poland; Yonsei Cancer Center, Seoul, Republic of Korea; Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil; Siriraj Hospital, Mahidol University, Bangkok, Thailand; Dnipropetrovsk Medical Academy, Dnipropetrovsk, Ukraine; Nippon Medical School Hospital, Tokyo, Japan; Merck & Co., Inc., Kenilworth, NJ; Chinese University of Hong Kong, Shatin, China
Background: In KEYNOTE-024, pembro significantly improved PFS (primary end point) and OS (secondary end-point) over chemo as first-line therapy for metastatic NSCLC without targetable alterations and PD-L1 TPS ≥50%. In KEYNOTE-042, we compared pembro with chemo at the lower TPS of ≥1% (NCT02220894). Methods: Eligible patients (pts) were randomized 1:1 to ≤35 cycles of pembro 200 mg Q3W or investigator’s choice of ≤6 cycles of paclitaxel + carboplatin or pemetrexed (peme) + carboplatin with optional peme maintenance (nonsquamous only). Randomization was stratified by region (east Asia vs non-east Asia), ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and TPS (≥50% vs 1-49%). Primary end-points were OS in pts with TPS ≥50%, ≥20%, and ≥1%. OS differences were assessed sequentially using the stratified log-rank test. Efficacy boundaries at the prespecified second interim analysis were one-sided P = .0122, .01198, and .01238, respectively. Results: 1274 pts were randomized: 637 to each arm. 599 pts (47.0%) had TPS ≥50%, 818 (64.2%) had TPS ≥20%. After 12.8-mo median follow-up, 13.7% were still on pembro and 4.9% were receiving peme maintenance. Pembro significantly improved OS in pts with TPS ≥50% (HR 0.69), TPS ≥20% (HR 0.77), and TPS ≥1% (HR 0.81) (Table). Grade 3-5 drug-related AEs were less frequent with pembro (17.8% vs 41.0%). The external DMC recommended continuing the trial to evaluate PFS (secondary end-point). Conclusion: KEYNOTE-042 is the first study with a primary end-point of OS to demonstrate superiority of pembro over platinum-based chemo in pts with previously untreated advanced/metastatic NSCLC without sensitizing EGFR or ALK alterations and a PD-L1 TPS ≥1%. These data confirm and potentially extend the role of pembro monotherapy as a standard first-line treatment for PD-L1-expressing advanced/metastatic NSCLC. Clinical trial information: NCT02220894
N = 299
N = 300
N = 413
N = 405
N = 637
N = 637
|HR (95% CI)||0.69 (0.56-0.85)||0.77 (0.64-0.92)||0.81 (0.71-0.93)|
|Median (95% CI), mo||20.0 |
3. IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC.