In KEYNOTE-189, a pembrolizumab/chemo combination yielded OS and PFS benefits in patients with advanced NSCLC.
The addition of the immune checkpoint inhibitor pembrolizumab to chemotherapy yielded significantly longer overall survival (OS) than chemotherapy alone in patients with newly diagnosed metastatic nonsquamous non–small-cell lung cancer (NSCLC), according to results of the phase III KEYNOTE-189 trial, which were recently published in the New England Journal of Medicine.
“The long-term survival of patients with advanced NSCLC remains poor and the standard of care for most patients is chemotherapy, which affords a survival benefit measured in months,” Leena Gandhi, MD, PhD, of the Perlmutter Cancer at New York University Langone Health, said in a press release. “Results from KEYNOTE-189 are practice-changing.”
Gandhi presented results of the study at the American Association for Cancer Research (AACR) Annual Meeting, held April 14–18 in Chicago (Abstract CT075). The trial included 616 patients with untreated stage IV nonsquamous NSCLC, with no sensitizing EGFR or ALK alterations. They were randomized to receive either pembrolizumab plus pemetrexed and carboplatin or cisplatin (410 patients), or placebo plus the same chemotherapy options (206 patients).
The median follow-up period was 10.5 months. The median OS was not reached in the pembrolizumab patients, compared with 11.3 months in the control group (hazard ratio [HR] for death, 0.49; 95% CI, 0.38–0.64; P < .00001). In total, 31.0% of patients in the pembrolizumab group died during the follow-up period, compared with 52.4% of patients randomized to chemotherapy plus placebo.
The benefit of the programmed death 1 (PD-1) inhibitor was seen despite programmed death ligand 1 (PD-L1) expression. Among patients with a PD-L1 tumor proportion score (TPS) of < 1%, the HR for OS was 0.59 (95% CI, 0.38–0.92; P = .0095). Among those with a TPS of 1% to 49%, the HR was 0.55 (95% CI, 0.34–0.90; P = .0081). And among those with a TPS of 50% or higher, the HR was 0.42 (95% CI, 0.26–0.68; P = .0001).
Progression-free survival (PFS) was also improved with pembrolizumab; 59.5% of patients in the group had a PFS event, compared with 80.6% of those in the placebo group, for an HR of 0.52 (95% CI, 0.43–0.64; P < .00001). This benefit was also seen across PD-L1 expression levels, though it was lowest among those with TPS < 1%.
In the full cohort, the response rate was 47.6% with pembrolizumab and 18.9% with placebo (P < .00001). The response rates were significantly better with pembrolizumab across PD-L1 expression levels.
Almost all patients in both groups experienced an adverse event(AE). Grade 3 to 5 AEs occurred in 67.2% of patients treated with pembrolizumab plus chemotherapy and in 65.8% of patients who received placebo plus chemotherapy; 6.7% and 5.9% of AEs, respectively, led to death. In the pembrolizumab group, 13.8% of patients had an AE that led to discontinuation of all treatment, compared with 7.9% in the placebo group.
There was a 5.2% incidence of acute kidney injury in the pembrolizumab-treated patients, compared with 0.5% in the placebo group; 2.0% and 0% of cases, respectively, were grade 3 to 5 in severity.
“This phase III trial demonstrated an improvement in overall response rate, PFS, and OS across all groups of patients, irrespective of PD-L1 expression, halving the risk of death, which is an unprecedented effect of therapy in the first-line setting for advanced nonsquamous NSCLC without EGFR or ALK alterations,” Gandhi said.