Abstract
Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at least 50%. However, little is known about the value of adding chemotherapy to pembrolizumab in this setting. Therefore, we performed an indirect comparison for pembrolizumab plus chemotherapy versus pembrolizumab, using the frequentist methods. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Data were retrieved from randomized trials comparing pembrolizumab plus chemotherapy or pembrolizumab monotherapy against chemotherapy. Five trials involving 1289 patients were included. Direct meta-analysis showed that both pembrolizumab plus chemotherapy (ORR: relative risk (RR) 2.16; PFS: hazard ratio (HR) 0.36; OS: HR 0.51) and pembrolizumab alone (ORR: RR 1.33; PFS: HR, 0.65; OS: HR 0.67) improved clinical outcomes compared with chemotherapy. Indirect comparison showed that pembrolizumab plus chemotherapy was superior to pembrolizumab alone, in terms of ORR (RR 1.62, 1.18–2.23) and PFS (HR 0.55, 0.32–0.97). A trend towards improved OS was also observed (HR 0.76, 0.51–1.14). In conclusion, the addition of chemotherapy to pembrolizumab further improves the outcomes of patients with advanced NSCLC and a PD-L1 TPS of at least 50%.
Highlights
With recent advance of immune checkpoint inhibitor treatment that blocks the Programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway, pembrolizumab monotherapy has replaced platinumdoublet chemotherapy as first-line treatment in patients with advanced non-small cell lung carcinoma (NSCLC) and a PD-L1 tumor proportion score (TPS) of 50% or more [1]
Direct meta-analysis Significant difference of objective response rate (ORR) was observed in favor of pembrolizumab plus chemotherapy versus chemotherapy (RRpem + chemo/chemo 2.16, 95% Confidence interval (CI) 1.66–2.82; P < 0.001; heterogeneity, P = 0.441)
The results indicated that patients treated with pembrolizumab plus chemotherapy had better clinical outcomes including ORR (RRpem + chemo/pem 1.62, 95% CI 1.18–2.23; P = 0.003) and progression-free survival (PFS) (HRpem + chemo/pem 0.55, 95% CI 0.32–0.97; P = 0.037) than those treated with pembrolizumab alone
Summary
With recent advance of immune checkpoint inhibitor treatment that blocks the PD-1 (programmed cell death 1) and PD-L1 (programmed cell death-ligand 1) pathway, pembrolizumab monotherapy has replaced platinumdoublet chemotherapy as first-line treatment in patients with advanced non-small cell lung carcinoma (NSCLC) and a PD-L1 tumor proportion score (TPS) of 50% or more [1]. Among patients with unselected PD-L1 expression, pembrolizumab plus chemotherapy is superior to chemotherapy alone [2]. Whether combination of pembrolizumab and chemotherapy could further improve the clinical outcomes compared with pembrolizumab. We evaluated the efficacy of pembrolizumab (pem) plus chemotherapy (chemo) versus pembrolizumab alone for the first-line treatment of patients with advanced NSCLC and a PD-L1 TPS of ≥50% using indirect comparison meta-analysis
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