Phase 3 KEYNOTE-789 Trial Evaluates Pembrolizumab Plus Chemotherapy in EGFR-Mutated, Metastatic NSCLC

Pembrolizumab plus chemotherapy does not significantly extend survival in patients with EGFR–mutated, metastatic nonsquamous non-small cell lung cancer (NSCLC) compared with chemotherapy alone, according to findings from the KEYNOTE-789 clinical trial.

The phase 3 global, multi-center trial included 492 patients with stage IV NSCLC with a documented DEL19 or L858R EGFR mutation, whose disease progressed following EGFR-directed tyrosine kinase inhibitor treatment. They were selected at random to receive pembrolizumab plus chemotherapy (n=245) or saline placebo plus chemotherapy (n=247). Chemotherapy consisted of pemetrexed and investigator’s choice of carboplatin or cisplatin.

Patients across both groups had similar demographic characteristics. Most participants were women, a median age of 63 years, and had an ECOG performance status of 0 or 1. Furthermore, most patients (66.1%) had never smoked.

Regarding disease characteristics, 20.9% of the patient population had tumors with PD-L1 tumor proportion score ≥ 50% and almost half (48.2%) had received osimertinib in the first- or second-line setting.

The researchers investigated progression-free survival (PFS) and overall survival (OS). Trial findings were published in the Journal of Clinical Oncology.

At the second interim analysis, the median PFS was 5.6 months in the pembrolizumab cohort versus 5.5 months for placebo (P = .0122). The median OS at final analysis was slightly better in the pembrolizumab cohort compared with placebo,15.9 months versus 14.7 months, respectively (P = .0362).

“[The] addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy,” the researchers said.

In addition, no new safety signals were observed in either of the 2 groups. Adverse events (AEs) of any kind occurred in 97.6% of patients in the pembrolizumab cohort and 98% of patients in the placebo cohort. Treatment-related AEs were seen in 89.8% of patients and 86.2% of patients, respectively. The most common TRAEs included anemia, decreased neutrophil count, and nausea.

Grade ≥ 3 TRAEs were seen in 43.7% of patients who received pembrolizumab compared with 38.6% of patients who were given placebo.

Three deaths occurred that were related to AEs from treatment. In the pembrolizumab cohort, 1 patient died from myocarditis. In the placebo cohort, 2 patients died (bone marrow failure and general physical health deterioration).

Source: JCO