Dr Yang on the Results of the KEYNOTE-789 Trial in EGFR-mutant NSCLC

James Chih-Hsin Yang, MD, director, professor, Graduate Institute of Oncology, the National Taiwan University, director, the Department of Oncology, the National Taiwan University Hospital, discusses the investigation of pembrolizumab (Keytruda) plus pemetrexed and platinum-based chemotherapy in patients with TKI-resistant, EGFR-mutant, metastatic nonsquamous non–small cell lung cancer (NSCLC).

Yang and colleagues presented data from the phase 3 KEYNOTE-789 study (NCT03820986) at the 2023 ASCO Annual Meeting, showing that treatment with pembrolizumab with chemotherapy prolonged progression-free survival (PFS) and overall survival (OS); however, the data did not reach statistical significance per the prespecified statistical analysis plan. At the second interim analysis, patients treated in the pembrolizumab arm (n = 245) experienced a median PFS of 5.6 months (95% CI, 5.5-5.8) vs 5.5 months (95% CI, 5.4-5.6) for those in the placebo plus chemotherapy arm (n = 247; HR, 0.80; 95% CI, 0.65-0.97; P = .0122). At the final analysis, the median OS was 15.9 months (95% CI, 13.7-18.8) for patients treated with pembrolizumab plus chemotherapy vs 14.7 months (95% CI, 12.7-17.1) for those given placebo plus chemotherapy (HR, 0.84; 95% CI, 0.69-1.02; P = .0362).

The large, randomized phase 3 study required patients to have had prior EGFR TKI treatment and disease progression per RECIST v1.1 criteria, Yang begins. Moreover, patients needed to EGFR exon 19 deletions or L858R mutations and an ECOG performance status of 0 or 1, he notes. Upon enrollment, patients were stratified according to PD-L1 expression (<50% vs ≥50%), by region (East Asia vs non-East Asia), and by prior treatment (osimertinib [Tagrisso] vs no osimertinib), Yang explains.

Patients were randomly assigned in a 1:1 fashion to pembrolizumab or placebo in combination with pemetrexed and carboplatin or cisplatin for 4 cycles, followed by maintenance pembrolizumab or placebo plus pemetrexed. Pembrolizumab was given for a total of 2 years, Yang continues. Notably, those who randomly assigned to the placebo arm were allowed to cross over to receive pembrolizumab monotherapy upon disease progression, Yang concludes.