Pembrolizumab Plus Chemotherapy Drives Durable PFS, OS Benefit in Squamous NSCLC

Pembrolizumab plus chemotherapy demonstrated sustained improvements in progression-free survival (PFS) and overall survival (OS) vs placebo plus chemotherapy in patients with treatment-naïve, metastatic squamous non–small cell lung cancer (NSCLC) regardless of PD-L1 expression level, according to 5-year data from the phase 3 KEYNOTE-407 trial (NCT02775435).

Data presented at the 2022 ESMO Congress showed that at a median follow-up of 56.9 months (range, 49.9-66.2), the median OS was 17.2 months (95% CI, 14.4-19.7) with pembrolizumab vs 11.6 months (95% CI, 10.1-13.7) with placebo (HR, 0.71; 95% CI, 0.59-0.85). The 5-year OS rates in the investigative and control arms were 18.4% and 9.7%, respectively.

The median PFS was 8.0 months (95% CI, 6.3-8.5) with pembrolizumab vs 5.1 months (95% CI, 4.3-6.0) with placebo (HR, 0.62; 95% CI, 0.52-0.74). The 5-year PFS rates in the investigative and control arms were 10.8% and 3.5%, respectively.

“Long-term data continue to support pembrolizumab plus chemotherapy as a standard-of-care first-line treatment option for metastatic squamous NSCLC,” lead study author Silvia Novello, MD, PhD, professor of medical oncology at the University of Turin, said in a presentation of the data.

Significant improvements in PFS and OS were previously reported with pembrolizumab vs placebo in findings from the primary (OS: HR, 0.64; 95% CI, 0.49-0.85; P < .001; PFS: HR, 0.56; 95% CI, 0.45-0.70; P < .001) and protocol-specified final analysis (OS: HR, 0.71; 95% CI, 0.58-0.88; PFS: HR, 0.57; 95% CI, 0.47-0.69) of the trial, which had been conducted at median follow-ups of 7.8 (range, 0.1-19.1) and 14.3 (range, 0.1-31.3) months, respectively.

At approximately 5 years, 50.9% (n = 117) of patients on the placebo arm had crossed over to receive pembrolizumab monotherapy on study and another 26 received subsequent anti–PD-(L)1 therapy off study.

Additional results showed that patients derived benefit from pembrolizumab regardless of whether they had PD-L1 expression below 1% (OS: HR, 0.83; 95% CI, 0.61-1.13; PFS: HR, 0.70; 95% CI, 0.52-0.95), between 1% and 49% (OS: HR, 0.61; 95% CI, 0.45-0.83; PFS: HR, 0.60; 95% CI, 0.45-0.81), or 50% or greater (OS: HR, 0.68; 95% CI, 0.47-0.97; PFS: HR, 0.48; 95% CI, 0.33-0.69).

In the intention-to-treat population, the objective response rate (ORR) was 62.2% with pembrolizumab (n = 278) vs 38.8% with placebo (n = 281). The median duration of response (DOR) in this population was 9.0 months (range, 1.3+ to 61.5+) with pembrolizumab vs 4.9 months (range, 1.3+ to 58.6+) with placebo.

Responses were similarly improved with pembrolizumab vs placebo in patients with PD-L1 expression below 1% (67.4% vs 41.4%), between 1% and 49% (54.4% vs 43.3%), and 50% or greater (64.4% vs 30.1%). The median DOR was also prolonged with pembrolizumab in each PD-L1 subset.

Notably, patients who completed all 35 cycles of pembrolizumab (n = 55) had “durable responses and experienced long-term OS,” Novello said. In this population, the ORR was 90.9% (95% CI, 80.0%-97.0%) and consisted of 9 (16.4%) complete responses and 41 (74.5%) partial responses. The median DOR in this population was not yet reached (range, 7.1-61.5+).

Additionally, the 3-year OS rate after completing 35 cycles of pembrolizumab was 69.5%, and 43.6% (n = 24) of patients were alive without progressive disease or subsequent therapy.

Regarding safety, 98.6% of those in the pembrolizumab arm (n = 278) experienced any adverse effects (AEs) vs 98.2% of those in the placebo arm (n = 280); these cases were grade 3 to 5 in 74.8% and 70.0% of patients, respectively. Immune-mediated toxicities occurred in 35.6% of those in the investigative arm vs 9.3% of those in the control arm; these effects were grade 3 to 5 in 13.3% and 3.2% of patients, respectively.

In the pembrolizumab arm, 28.8% of patients experienced toxicities that resulted in discontinuation of any treatment, 17.2% experienced AEs that led to discontinuation of all treatments, and 11.5% experienced AEs that resulted in death.

“Toxicity was manageable and consistent with prior reports from KEYNOTE-407,” Novello concluded.

Reference

Novello S, Kowalski DM, Luft A, et al. 5-year update from KEYNOTE-407: pembrolizumab plus chemotherapy in squamous non–small-cell lung cancer. Ann Oncol. 2022;33(suppl 7):S993-S994. doi:10.1016/j.annonc.2022.07.1102