KEYNOTE-407 supports pembrolizumab–chemotherapy combination for metastatic squamous NSCLC
medwireNews: Survival outcomes are improved with the addition of pembrolizumab to chemotherapy in patients with untreated, metastatic nonsquamous non-small-cell lung cancer (NSCLC), indicate findings from the phase III KEYNOTE-407 trial.
In the second interim analysis – conducted at a median follow-up of 7.8 months – the co-primary endpoint of overall survival was a median of 15.9 months for the 278 participants who were randomly assigned to receive pembrolizumab 200 mg for up to 35 cycles alongside carboplatin plus paclitaxel or nanoparticle albumin-bound (nab)-paclitaxel for the first four cycles.
This was significantly longer than the median of 11.3 months achieved by the patients given placebo plus chemotherapy and equated to a hazard ratio (HR) for death of 0.64.
Progression-free survival, the other primary endpoint, was also prolonged with the addition of the PD-1 inhibitor to chemotherapy, at a median of 6.4 months versus 4.8 months with chemotherapy alone, and an HR for disease progression or death of 0.56.
Luis Paz-Ares (Hospital Universitario 12 De Octubre, Madrid, Spain) and co-researchers note that improvements in both endpoints were seen across all prespecified subgroups, including by PD-L1 expression. For instance, the HR for death was 0.61 for patients with a PD-L1 tumor proportion score (TPS) of less than 1%, 0.57 for a TPS of 1–49%, and 0.64 for a TPS of at least 50%. They point out, however, that the upper limit of the 95% confidence interval for the last group exceeded 1.
The adverse events (AEs) were “as expected” for the agents, with no new safety signals, reports the team. Grade 3 or worse AEs occurred in a comparable 69.8% and 68.2% of patients in the pembrolizumab and placebo groups, respectively, and led to discontinuation of all treatment components in a corresponding 12.2% and 6.4% of participants, and to death in 8.3% and 6.4%.
The investigators suggest that the higher rate of discontinuation in the pembrolizumab study arm could partly be attributed to the longer duration of treatment, at an average of 6.3 months versus 4.7 months for the placebo group.
They write in The New England Journal of Medicine that these results alongside those of three other phase III trials “suggest that pembrolizumab has a role in the first-line treatment of metastatic NSCLC, regardless of histologic subtype or PD-L1 tumor proportion score.”
The pembrolizumab–chemotherapy combination “has shown a high level of activity” in patients with PD-L1-negative tumors, but the findings are less clear for PD-L1-positive tumors, say Paz-Ares et al.
“Therefore, the treatment decision should be made on an individual basis after a discussion of the relative risks and benefits and consideration of patient-specific factors,” they conclude.
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