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

Author(s):

January 28, 2021 — Frontline pembrolizumab continued to demonstrate clinically meaningful improvements in overall survival, overall response rate, and time to progression on next-line therapy compared with platinum-based chemotherapy in patients with locally advanced or metastatic PD-L1–positive non–small cell lung cancer without sensitizing EGFR or ALK mutations.

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

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.