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01-12-2019 | NSCLC | PHASE III STUDIES

Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001)

Authors: Motohiro Tamiya, Akihiro Tamiya, Kazutaka Hosoya, Yoshihiko Taniguchi, Toshihide Yokoyama, Yasushi Fukuda, Katsuya Hirano, Hirotaka Matsumoto, Ryota Kominami, Hidekazu Suzuki, Tomonori Hirashima, Junji Uchida, Mitsunori Morita, Masaki Kanazu, Nobuhiko Sawa, Yoshinori Kinoshita, Satoshi Hara, Toru Kumagai, Daichi Fujimoto

Published in: Investigational New Drugs | Issue 6/2019

Summary

Objectives As first line therapy, pembrolizumab provides longer progression free survival (PFS) and overall survival (OS) than platinum doublets in programmed death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) with tumor propensity scores (TPS) ≥50%. However, clinical trials do not represent real-world patients. Materials and Methods This multicenter retrospective study conducted across 11 medical centers in Japan analyzed clinical data from patients receiving first-line pembrolizumab for NSCLC between February 1, 2017 and April 30, 2018. The efficacy, safety, and suitability of pembrolizumab monotherapy were evaluated. Results The median age of the 213 enrolled patients was 71 (range: 39–91) years. Among them, 176 (82.6%) were male, 20 (9.4%) were never smokers (median Brinkman index: 900), 172 (80.8%) had an ECOG PS of 0–1, 55 (25.8%) had squamous-cell carcinoma (SQ). PD-L1 TPS were 50–74%, 75–89%, and 90–100% in 97 (45.5%), 47 (22.1%), and 69 (32.4%) patients, respectively. Adverse events (AEs) of grades ≥3 were observed in 39 (18.3%) patients. Pneumonitis was the most common severe AE, occurring in 10 patients (4.7%) including 1 with grade 4 toxicity; no severe AE-related deaths occurred. The overall response rate, median PFS, and median OS was 51.2%, 8.3 months, and 17.8 months, respectively. On multivariate analysis, ECOG PS (0–1 vs. ≥2: HR: 1.69, 95.0% CI: 1.05–2.72; p = 0.03138), CRP/Alb (<0.3 vs. ≥0.3: HR: 1.92, 95.0% CI: 1.28–2.87; p = 0.00153), steroid usage (not usage vs. usage: HR: 2.94, 95.0% CI: 1.45–5.95; p = 0.00267), and PD-L1 TPS (50–89% vs. 90–100%: HR: 0.65, 95.0% CI: 0.43–1.00; p = 0.04984) were significantly and independently correlated with PFS of pembrolizumab. Conclusion The results confirm the efficacy and safety of pembrolizumab in real-world patients. Poor PS and steroid usage at the time of commencing pembrolizumab treatment indicate poor outcomes. First-line pembrolizumab particularly benefits patients with PD-L1 TPS ≥90% or low inflammatory states (CRP/ALB<0.3).

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Title: Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001)
Authors: Motohiro Tamiya
Akihiro Tamiya
Kazutaka Hosoya
Yoshihiko Taniguchi
Toshihide Yokoyama
Yasushi Fukuda
Katsuya Hirano
Hirotaka Matsumoto
Ryota Kominami
Hidekazu Suzuki
Tomonori Hirashima
Junji Uchida
Mitsunori Morita
Masaki Kanazu
Nobuhiko Sawa
Yoshinori Kinoshita
Satoshi Hara
Toru Kumagai
Daichi Fujimoto
Publication date: 01-12-2019
Publisher: Springer US
Keywords: NSCLC
NSCLC
Published in: Investigational New Drugs / Issue 6/2019
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00843-y

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