Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small cell lung cancer and a poor performance status.

Background: Patients with non-small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) have been excluded from phase III immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 Tumor Proportion Score (TPS) of ≥50%, and an ECOG PS of 2.
Methods: We performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 TPS of ≥50% (negative for genomic alterations in EGFR and ALK ) who received treatment with first-line pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS.
Results: Among the 234 patients, 83.3% (n=195) had an ECOG PS of 0 or 1, and 16.7% (n=39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0-1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations ( BRAF, MET, HER2, RET ), presence of brain metastases, and PD-L1 TPS distribution. Compared with patients with an ECOG PS of 0 or 1, patients with an ECOG PS of 2 had a significantly lower objective response rate (43.1% vs 25.6%; p=0.04), a numerically shorter median progression-free survival (6.6 months vs 4.0 months; HR 0.70 (95% CI 0.47 to 1.06); p=0.09), and a significantly shorter median overall survival (20.3 months vs 7.4 months; HR 0.42 (95% CI 0.26 to 0.68); p<0.001). On disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared with patients with an ECOG PS of 0-1 (65% vs 22.2%, p=0.001).
Conclusions: A subset of patients with NSCLC and an ECOG PS of 2 can respond to first-line pembrolizumab. However, clinical outcomes in this population are often poor and use of second-line systemic therapy is infrequent.
Competing Interests: Competing interests: MMA serves as a consultant to Merck, Bristol-Myers Squibb, Genentech, AstraZeneca, Nektar, Ariad, Maverick, Blueprint Medicine, Syndax, Abbvie, and Gridstone. Research Funding: Bristol-Myers Squibb, Lilly, Genentech and AstraZeneca. MA serves as scientific advisory boards for GSK and Shattuck Lab. Research funding: GSK, Bristol-Myers Squibb, Genentech, Nektar, Jounce, Lilly, Adaptimmune, Novartis. FH: consultant to Merck. JVH serves as consultant to AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Guardant Health, Kairos Venture Investments, BrightPath Biotherapeutics, Hengrui Therapeutics, Eli Lilly, Spectrum, EMD Serono, Roche, Foundation One Medicine. Research grant from NIH/NCI, American Cancer Society, Cancer Prevention & Research Institute of Texas, AACR Johnson & Johnson Lung Cancer, AstraZeneca, Spectrum, Checkmate Pharmaceuticals. Royalties from Bio-Tree Systems, Inc. In addition, Dr Heymach has a patent held by Spectrum with royalties paid. MN serves as consultant to Daiichi Sankyo. Research grant from Merck and AstraZeneca. Honorarium from Roche. NIH funding (R01CA203636, U01CA209414, R01HL111024). MDH: research funding from Bristol-Myers Squibb. Consultant to Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Immunai, Syndax, Mirati, Nektar, Blueprint, Archilles, Arcus, Pact Pharma and Shattuck Labs. A patent has been filed by MSK related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx.
(© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)