Chicago, IL—Two new clinical trials with overall survival (OS) as the primary end point establish pembrolizumab (Keytruda) as a front-line standard of care in patients with non–small-cell lung cancer (NSCLC). The results were presented at ASCO 2018.
In one of the studies, pembrolizumab extended OS compared with platinum-based chemotherapy in patients with untreated, advanced or metastatic NSCLC, even in those with low levels of PD-L1 expression, said Gilberto Lopes, Jr, MD, MBA, CoLeader, Lung Cancer Site Disease Group, Sylvester Comprehensive Cancer Center, University of Miami Health System, FL, and lead investigator of the open-label phase 3 KEYNOTE-042 study.
In the second study, front-line pembrolizumab therapy combined with conventional chemotherapy prolonged the OS compared with chemotherapy alone in patients with metastatic, squamous NSCLC, according to data from the global phase 3 KEYNOTE-407 trial.
KEYNOTE-042: Monotherapy Benefit Across PD-L1 Levels
In KEYNOTE-042, 1274 patients with advanced NSCLC and PD-L1 ≥1% were randomized to up to 35 cycles of pembrolizumab or up to 6 cycles of investigator's choice of paclitaxel plus carboplatin or pemetrexed plus carboplatin with optional pemetrexed maintenance. Eligible patients did not have sensitizing EGFR or ALK alterations. The investigators looked at results stratified by PD-L1 levels of ≥50%, ≥20%, or ≥1%.
After a median follow-up of 12.8 months, the median OS in the full cohort (PD-L1 ≥1%) was 16.7 months in the pembrolizumab arm and 12.1 months in the chemotherapy arm (hazard ratio [HR], 0.81; P = .0018). In those with PD-L1 ≥20%, the median OS was 17.7 months and 13.0 months, respectively (HR, 0.77; P = .002), and in patients with PD-L1 ≥50%, the median OS was 20.0 months with pembrolizumab and 12.2 months with chemotherapy (HR, 0.69; P = .0003).
Despite a greater median number of doses of pembrolizumab versus chemotherapy (9 vs 6), the rate of treatment-related adverse events was greater with chemotherapy (89.9%) than with pembrolizumab (62.7%). Grade 3 to 5 adverse events were 41.0% in the chemotherapy arm and 17.8% in the pembrolizumab arm.
"Pembrolizumab becomes an option for patients who have advanced NSCLC who do not have EGFR mutations or ALK translocations, and who express PD-L1 at least at that 1% level," said Dr Lopes.
ASCO Expert John Heymach, MD, PhD, Chair, Department of Thoracic/Head and Neck Medical Oncology, M.D. Anderson Cancer Center, Houston, commented that the OS improvement with lower toxicity constituted a "double win" for pembrolizumab in this setting.
"The majority of patients with NSCLC can start their treatment without chemotherapy," Dr Heymach said.
KEYNOTE-407: Combination Better for Squamous NSCLC
In KEYNOTE-407, 559 patients with untreated, metastatic squamous NSCLC were randomized to 4 cycles of carboplatin and paclitaxel (Taxol) or nab-paclitaxel (Abraxane) plus pembrolizumab or placebo. Maintenance therapy was pembrolizumab or placebo, according to patients' original treatment assignments. Patients in the placebo arm whose disease progressed could cross over to pembrolizumab monotherapy at any time.
At a second interim analysis at a median follow-up of 7.8 months, the median OS was 11.3 months in the carboplatin and paclitaxel or nab-paclitaxel arm and improved to 15.9 months with the addition of pembrolizumab to chemotherapy (HR, 0.64; P = .0008). The OS advantage of adding pembrolizumab was evident across patient subgroups, including those with low PD-L1 expression (<1%; HR, 0.61), intermediate (1%-49%; HR, 0.57), or high (≥50%; HR, 0.64).
The median progression-free survival was also superior with pembrolizumab plus chemotherapy versus chemotherapy alone in the entire cohort (6.4 months vs 4.8 months, respectively; HR, 0.56; P <.0001) and across all PD-L1 expression subgroups.
"These data suggest pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel should become a new standard of care for the first-line treatment of metastatic squamous NSCLC across all the different levels of PD-L1 expression," said lead investigator Luis G. Paz-Ares, MD, PhD, Hospital Universitario 12 de Octubre, Madrid, Spain, who presented the results.
The rate of adverse events was similar between the pembrolizumab plus chemotherapy arm and the chemotherapy-alone arm when examining overall events (98.2% vs 97.9%) and grade 3 to 5 events (69.8% vs 68.2%).