KEYNOTE-042: Pembrolizumab monotherapy supported for PD-L1-positive advanced NSCLC
medwireNews: Overall survival (OS) is significantly longer with single-agent pembrolizumab than with platinum-based chemotherapy in patients with previously untreated, locally advanced or metastatic non-small-cell lung cancer (NSCLC) that has programmed cell death ligand 1 (PD-L1) expression levels of at least 1%, according to the KEYNOTE-042 results.
The 1274 EGFR- and ALK-negative patients recruited to the phase III trial were randomly assigned to receive either pembrolizumab – at a dose of 200 mg every 3 weeks for up to 35 cycles – or chemotherapy with carboplatin alongside paclitaxel or pemetrexed, and followed up for a median 12.8 months. As per the statistical design, OS was tested sequentially in patients with a PD-L1 tumor proportion score (TPS) of at least 50%, at least 20%, and at least 1%.
In the subgroup of participants with a TPS of at least 50%, OS was a median of 20.0 months for pembrolizumab-treated patients and 12.2 months for those given chemotherapy, equating to a significant hazard ratio (HR) in favor of pembrolizumab of 0.69.
Pembrolizumab likewise afforded an OS advantage over chemotherapy in the subgroups with a TPS of at least 20% and at least 1%, at a median of 17.7 versus 13.0 months and 16.7 versus 12.1 months, respectively. The corresponding HRs for the comparisons were 0.77 and 0.81.
This benefit was also observed across all other subgroups, with the exception of those who were never or current smokers, presenter Gilberto Lopes (Sylvester Comprehensive Cancer Center at the University of Miami, Florida, USA) told the attendees of the ASCO Annual Meeting 2018, held in Chicago, Illinois, USA.
By contrast, pembrolizumab treatment was not associated with a significant progression-free survival improvement in patients with a TPS of at least 50%, and this precluded additional analyses in the other TPS subgroups, he added.
The incidence of grade 3–5 treatment-related adverse events was lower with the PD-1 inhibitor than chemotherapy, at 17.8% and 41.0%, respectively, but the rates of toxicities leading to discontinuation (9.0 vs 9.4%) or death (2.0 vs 2.3%) were comparable.
Unsurprisingly, immune-mediated adverse events and infusion reactions occurred more often in the pembrolizumab than in the chemotherapy group, with grade 3–5 events seen in a respective 8.0% and 1.5% of participants.
Speaking to medwireNews about the implications of these results in this population with at least 1% PD-L1 expression, Lopes noted that the findings make “pembrolizumab monotherapy an option for patients who want to avoid chemotherapy toxicity and who have low volume of disease.”
For those with high volume of disease or those who may miss the opportunity of receiving chemotherapy in the second line, the combination of pembrolizumab and chemotherapy would be the preferred option, for both nonsquamous and squamous histology in light of the recent KEYNOTE-189 and -407 results, he continued.
Lopes stressed that patients with PD-L1 expression below 1% “should absolutely not” be given single-agent pembrolizumab; for them, combining pembrolizumab with chemotherapy may be the better option.
“Moreover, many patients with PD-L1 of less than 1% may have a tumor mutational burden of 10 per megabyte and might be candidates for the combination of nivolumab and ipilimumab,” noted Lopes.
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