medwireNews: Patients with extensive-stage small-cell lung cancer (SCLC) derive a progression-free survival (PFS) benefit from first-line treatment with pembrolizumab plus chemotherapy, show phase 3 KEYNOTE-604 trial findings.
Presenting the data at the virtual 2020 ASCO Annual Meeting, Charles Rudin (Memorial Sloan Kettering Cancer Center, New York, USA) highlighted that overall survival (OS) also appeared to be extended with the addition of pembrolizumab, “but this result narrowly missed the predefined statistical threshold.”
Charles Rudin discusses the findings of the KEYNOTE-604 trial in the context of the previous IMpower133 and CASPIAN studies (5:01)
In the trial, 453 patients who had not received prior systemic therapy for stage IV disease were randomly assigned to receive either pembrolizumab 200 mg once every 3 weeks or placebo alongside four cycles of etoposide 100 mg/m2 on days 1 and 3, and physician’s choice of carboplatin AUC 5 or cisplatin 75mg/m2 on day 1.
The final analysis of the co-primary endpoint of median PFS – conducted at the second interim analysis at a median of 13.5 months – showed a significant improvement with the addition of pembrolizumab versus placebo to chemotherapy, at 4.5 and 4.3 months, respectively, and a hazard ratio (HR) for progression or death of 0.75. The corresponding estimated 12-month PFS rates were 13.6% and 3.1%.
The other primary endpoint of OS was evaluated at the final analysis at a median follow-up of 21.6 months and also favored the pembrolizumab group, with a median duration of 10.8 months versus 9.7 months for the placebo group, and an HR for death of 0.78. But the between-group difference did not meet the criteria for statistical significance specified in the trial protocol.
The 12-month OS rates in the pembrolizumab and placebo arms were 46.0% and 39.9%, respectively, with corresponding 24-month rates of 23.0% and 11.3%.
In subgroup analyses, the PFS and OS benefits associated with the addition of pembrolizumab persisted across all groups with the exception of patients who had brain metastases at baseline.
Rudin pointed out that the safety profile of the pembrolizumab combination was “manageable with no new or unexpected toxicities.” Pembrolizumab-treated patients were more likely to discontinue treatment due to adverse events (AEs) than those given placebo (14.8 vs 6.3%), but the rates of grade 3–4 (76.7 vs 74.9%) and grade 5 (6.3 vs 5.4%) AEs were similar.
However, the incidence of immune-mediated AEs was higher in the pembrolizumab than placebo group, with events of grade 3–4 occurring in 7.2% and 1.3% of patients, respectively.
“Taken together, these data support the benefit of pembrolizumab in patients with small-cell lung cancer and add to the growing body of evidence supporting the value of immune checkpoint inhibitors in a historically difficult to treat cancer,” said Rudin.
He added: “I believe additional correlative analyses may help to identify those patients who derive long-term benefit from pembrolizumab.”
The KEYNOTE-604 trial findings were simultaneously published in the Journal of Clinical Oncology.
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2020 ASCO Annual Meeting; 29–31 May
J Clin Oncol 2020; doi:10.1200/JCO.20.00793