Long-term follow up on the KEYNOTE-604 study suggests pembrolizumab plus etoposide/platinum is a superior first-line therapy for small cell lung cancer vs placebo.
Researchers are continuing to explore pembrolizumab-based combinations for patients with extensive stage small cell lung cancer (EP-SCLC). This succeeds a long-term follow up of patients in the KEYNOTE-604 study administered pembrolizumab and etoposide/platinum (EP) as a first-line treatment of EP-SCLC.
In the original phase 3 portion of the KEYNOTE-604 study, researchers examined the efficacy of administering pembrolizumab and EP vs taking EP plus placebo as a first-line therapy for ES-SCLC. Although the pembrolizumab plus EP cohort had more significant progression-free survival (PFS), it did not meet the threshold of statistical significance.
The primary endpoints of the trial were overall survival (OS) and PFS in the pembrolizumab plus EP group [intent-to treat (ITT) population]. Although study did not meet these endpoints, the data suggest there was still meaningful improvement, according to the study authors.
Charles Rudin, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York City updated the results of the KEYNOTE-604 study. Rudin and team achieved this after examining 453 randomized and previously untreated patients with ES-SCLC in the pembrolizumab plus EP population for approximately 3.5 years after their treatment.
Eligible patients with untreated ES-SCLC were randomized 1:1 and given either 200 mg of pembrolizumab or placebo for 35 cycles maximum, plus 4 cycles of standard-dose EP. Among both cohorts, 228 patients were administered the pembrolizumab plus EP combination and 225 were administered placebo plus EP.
In the KEYNOTE study, 54.8% of the pembrolizumab group followed their treatment with therapy, whereas 66.2% of the placebo group received subsequent therapy. A little more than 3 years later, the pembrolizumab group was shown to have improved OS and PFS. Patients treated with pembrolizumab plus EP also had a 3-year OS rate of 15.5%, compared to 5.9% for the placebo group.
“Pembrolizumab and EP continued to show clinically meaningful improvement in survival and manageable safety versus placebo plus EP in patients with previously untreated ES-SCLC; 3-year overall survival rate was over 2 and a half times higher among patients who received pembrolizumab and EP,” Rudin said in a press release.
The pembrolizumab group did experience a higher percentage of grade 3-5 adverse events (AE). AEs were reported in 78.9% of the pembrolizumab cohort vs 77.1% of the placebo group. From randomization to database cutoff, 18 patients in the ITT population completed all 35 cycles of pembrolizumab, however only 14 lived through the final assessments.
“Patients who completed 35 cycles of pembrolizumab had durable responses. Data support the continued exploration of pembrolizumab-based combinations for patients with small cell lung cancer,” Rudin concluded.
First-line pembrolizumab or placebo combined with etoposide and platinum for ES-SCLC: KEYNOTE-604 Long-Term. EurekAlert! Aug 9, 2022. Accessed on Aug 9, 2022. https://www.eurekalert.org/news-releases/960815