Frontline Pembrolizumab Maintains Survival Benefit Over Chemo in PD-L1+ NSCLC

Byoung Chul Cho, MD, PhD

Frontline pembrolizumab (Keytruda) continued to demonstrate clinically meaningful improvements in overall survival (OS), overall response rate (ORR), and time to progression on next-line therapy (PFS-2) compared with platinum-based chemotherapy in patients with locally advanced or metastatic PD-L1–positive non–small cell lung cancer (NSCLC) without sensitizing EGFR or ALK mutations, according to updated long-term data from the phase 3 KEYNOTE-042 trial that were presented during the 2020 World Conference on Lung Cancer Singapore.

Patients who completed 35 cycles of pembrolizumab treatment saw durable responses, and many patients experienced a continued response after the completion of therapy. A second course pembrolizumab was found to be feasible and was also associated with antitumor activity.

“These findings continue to support first-line pembrolizumab in patients with locally advanced/metastatic PD-L1–positive NSCLC without sensitizing EGFR/ALK alterations,” explained lead investigator, Byoung Chul Cho, MD, PhD, in a virtual presentation of the data.

Median OS data for patients in the 50% or higher PD-L1 tumor proportion score (TPS) group treated with pembrolizumab was 20.0 months (95% CI, 15.9-24.2) compared with 12.2 months (95% CI, 10.4-14.6) for patients in the chemotherapy group (HR, 0.68; 95% CI, 0.57-0.82). Moreover, the 3-year OS rate was 31.3% (95% CI, 26.1%-36.6%) for the pembrolizumab group and 18.4% (95% C1, 14.2%-23.0%) for the chemotherapy group.

For the 20% or higher PD-L1 TPS group, patients on pembrolizumab experienced a median OS of 18.0 months (95% CI, 15.5-21.5) compared with 13.0 months (95% CI, 11.6-15.3) for patients on chemotherapy (HR, 0.75, 95% CI, 0.64-0.88). The 3-year OS rates were 28.3% (95% CI, 24.1%-32.8%) for the pembrolizumab group and 18.8% (95% CI, 15.1%-22.8%) for the chemotherapy group.

In the 1% or higher PD-L1 TPS cohort, the pembrolizumab group saw a median OS of 16.4 months (95% CI, 14.0-19.6) compared with the chemotherapy group at 12.1 months (95% CI, 11.3-13.3; HR, 0.80; 95% CI, 0.71-0.90). The 3-year OS rates were 25.3% (95% CI, 22.0%-28.7%) and 16.7% (95% CI, 13.8%-19.7%), respectively.

“In the KEYNOTE-042 study, pembrolizumab significantly improved OS versus platinum-based chemotherapy as first-line treatment for locally advanced/metastatic NSCLC without sensitizing EGFR/ALK alterations with PD-L1 tumor proportion score greater than 1%,” Chu explained.

Median PFS in the TPS 50% or greater group was also measured, with no numerical differences noted (HR, 0.85; 95% CI, 0.71-1.02). However, at 3 years, the rate of PFS was higher in the pembrolizumab arm at 14.5% (95% CI, 10.5%-19.0%) versus 5.3% (95% CI, 3.0%-8.7%) with chemotherapy.

Similarly, median PFS was numerically similar between the pembrolizumab and chemotherapy arms in the other groups stratified by TPS. In those with a TPS of 20% or greater, the 3-year PFS rate was higher at 13.2% (95% CI, 10.0%-16.9%) in the pembrolizumab group compared with 4.7% (95% CI, 2.7%-7.5%) for patients undergoing chemotherapy. In those with a TPS of 1% or greater, the 3-year PFS rate was recorded at 11.0% (95% CI, 8.6%-13.7%) for the pembrolizumab group and 4.1% (95% CI, 2.6%-6.2%) for the chemotherapy group.

Median PFS2 was recorded at 15.0 months (95% CI, 11.6-19.2) in the pembrolizumab group compared with 10.1 (95% CI, 8.9-11.2) in the chemotherapy group in those with a PD-L1 TPS of 50% or more (HR, 0.62; 95% CI, 0.52-0.74). For PD-L1 TPS of 20% or more, median PFS2 was 12.9 months (95% CI, 10.9-15.5) for pembrolizumab versus 10.2 months (95% CI, 9.0-11.3) for chemotherapy (HR, 0.66; 95% CI, 0.57-0.77). Finally, median PFS2 was 11.3 months (95% CI, 10.1-12.9) for the pembrolizumab cohort compared with 9.3 months (95% CI, 8.6-10.2) in the chemotherapy group for PD-L1 TPS of 1% or greater (HR, 0.73; 95% CI, 0.65-0.82).

The group of eligible patients (N = 1274) were randomized 1:1 to receive either 200 mg of pembrolizumab every 3 weeks for up to 35 weeks or platinum-based therapy. The patients randomized to the pembrolizumab group who completed the 35 treatment cycles or had confirmed complete response were eligible to receive a second course of pembrolizumab.

The primary end point of the research was OS in by PD-L1 TPS by groups of 50% or more, 20% or more, and 1% or more. Secondary end points were PFS and ORR in all expression groups and safety in the TPS 1% or greater group.

“In the primary analysis, pembrolizumab significantly improved the primary end point of overall survival in all 3 TPS populations,” said Cho.

Reference

1. Cho BC, Wu YL, Lopes G, et al. KEYNOTE-042 3-Year Survival Update: 1L Pembrolizumab vs Platinum-Based Chemotherapy for PD-L1+ Locally Advanced/Metastatic NSCLC. Presented at: 2020 World Conference on Lung Cancer Singapore. January 27-31, 2021. Abstract FP13.04.