Pembrolizumab Plus Chemotherapy For Metastatic NSCLC With PD-L1 TPS <1%

Combining pembrolizumab with chemotherapy has been shown to significantly enhance both overall survival (OS) and progression-free survival (PFS) in metastatic NSCLC patients (pts) without EGFR or ALK alterations, regardless of their PD-L1 tumor proportion score (TPS). The study presented 5-year results from an analysis of phase 3 trials focusing on those with a PD-L1 TPS of less than 1%.

This consolidated analysis incorporated patient data from the global KEYNOTE-189 study (NCT02578680; last update on March 8, 2022) and its extension in Japan (NCT03950674; last updated on February 7, 2023), along with the KEYNOTE-407 global study (NCT02775435; last updated on February 23, 2022) and its extension in China (NCT03875092; last updated on February 10, 2023). KEYNOTE-189 involved treatment with pembrolizumab (or a placebo) alongside pemetrexed and either cisplatin or carboplatin. In contrast, KEYNOTE-407 used pembrolizumab (or a placebo) with carboplatin and either paclitaxel or nab-paclitaxel. PD-L1 levels were measured centrally, while tumor responses were gauged following the RECIST 1.1 criteria by a blinded independent review. The main focus for efficacy was the intention-to-treat population, and safety was gauged in the treated groups. This analysis is descriptive and was conducted post hoc.

Of the 442 pts with a PD-L1 TPS below 1% considered in this study, 255 (57.7%) were treated with pembrolizumab and chemotherapy, while 187 (42.3%) received only chemotherapy. While baseline characteristics were generally consistent between groups, there was a notable difference in tumor type; squamous tumors were present in 43.5% of the pembrolizumab and chemotherapy group and 63.6% of the chemotherapy-alone group. From the time of random assignment to the data cutoff, the median duration was 60.7 months. Notably, all outcomes – OS, PFS, ORR, and PFS2 – were superior in the pembrolizumab and chemotherapy group. Treatment-related adverse events (TEAEs) were observed in 96.5% of the pembrolizumab and chemotherapy group and 94.1% of the chemotherapy-alone group. Of these, grade 3 or above events were reported in 59.1% and 61.3% of the groups, respectively.

After 5 years of follow-up, pembrolizumab with chemotherapy demonstrated meaningful enhancements in survival outcomes and provided durable long-term clinical advantages over chemotherapy alone in metastatic NSCLC patients with a PD-L1 TPS below 1%. These findings further reinforce the choice of pembrolizumab with chemotherapy as a frontline treatment for metastatic NSCLC, including in tumors with a PD-L1 TPS of under 1%.

Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/961

Clinical Trials: https://classic.clinicaltrials.gov/ct2/show/NCT02578680

https://classic.clinicaltrials.gov/ct2/show/NCT03950674

https://classic.clinicaltrials.gov/ct2/show/NCT02775435

https://classic.clinicaltrials.gov/ct2/show/NCT03875092

Gadgeel, S., Rodríguez-Abreu, D., Halmos, B., Garassino, M.C., Kurata, T., Cheng, Y., Jensen, E., Shamoun, M., Rajagopalan, K., Paz-Ares, L. 5-Year Survival of Pembrolizumab Plus Chemotherapy for Metastatic NSCLC With PD-L1 Tumor Proportion Score <1%.