Anti–PD-(L)-1 Monotherapy versus Combination with Chemotherapy in Patients with PD-L1–High Lung Cancer

Anti–PD-(L)-1 monotherapy and in combination with chemotherapy are both standard first-line regimens for patients with PD-L1–high (≥50%) metastatic non–small-cell lung cancer (NSCLC).¹ The efficacy of these treatment options has not been assessed prospectively.¹ In addition, molecular tumor characteristics that are differentially associated with response to anti–PD-(L)-1 monotherapy compared with combination treatment with chemotherapy are not well-defined.¹

This study included patients with EGFR- and ALK-negative metastatic NSCLC treated with anti–PD-(L)-1 monotherapy or in combination with chemotherapy at Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. The study excluded patients with PD-L1 expression <50%, and those treated with immune checkpoint inhibitors (ICIs) or chemoimmunotherapy in the first-line or higher setting. The goals of the study were to compare overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) and investigate potential clinical, pathologic, and molecular response correlates. Tumor mutational burden (TMB) values were harmonized using a z-score conversion.¹

Of the 639 patients with stage IV EGFR/ALK wild-type NSCLC and PD-L1 ≥50% treated in the first-line setting, 504 received pembrolizumab and 135 received pembrolizumab plus chemotherapy. Patient baseline characteristics, including Eastern Cooperative Oncology Group performance status, median PD-L1 expression, and TMB were balanced between both treatment groups. Moreover, there was no difference between the groups in PD-L1 expression, TMB, or mutational (KRAS, STK11, or KEAP1) profile. Never-smokers with durable responses (>6 months) were less common in the monotherapy group (6% vs 18%; P <.001).

There was no significant difference in OS among patients treated with pembrolizumab monotherapy or in combination with chemotherapy (hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.6-1.08; P = .2). However, patients in the ICI monotherapy group had a shorter median PFS (HR, 0.7; 95% CI, 0.6-0.9; P = .004) and lower ORR compared with the chemoimmunotherapy group (40% vs 55%; P = .002).

The investigators concluded that the addition of chemotherapy to ICI in patients with PD-L1–high NSCLC did not improve OS compared with ICI monotherapy. Furthermore, there were no apparent differences in PD-L1 expression or molecular features associated with durable response to ICI monotherapy compared with the chemotherapy combination.

Reference

1. Elkrief A, Alessi J, Ricciuti B, et al. Outcomes of single-agent PD-(L)-1 versus combination with chemotherapy in patients with PD-L1-high (≥50%) lung cancer. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 9052.