Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non–small cell lung cancer and a poor performance status
Joao V. Alessi, Biagio Ricciuti, E. Jimenez-Aguilar, Fangxin Hong, Zihan Wei, Mizuki Nishino, Andrew J. Plodkowski, Peter Sawan, Jia Luo, Hira Rizvi, Brett W. Carter, John V. Heymach, Mehmet Altan, Matthew D. Hellmann, Mark M. Awad
Abstract
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.