Adjuvant pembrolizumab extends DFS in resected early-stage non-small cell lung cancer
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Pembrolizumab significantly extended DFS among patients with completely resected stage IB to stage III non-small cell lung cancer, irrespective of PD-L1 expression, according to a study presented during an ESMO Virtual Plenary session.
Results of the randomized phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS, further showed the anti-PD-1 antibody had a safety profile consistent with that observed in prior studies.
Rationale and methodology
Pembrolizumab (Keytruda, Merck) has become a standard of care for advanced NSCLC. The KEYNOTE-091 trial investigated use of the agent vs. placebo in the adjuvant setting for patients with completely resected stage IB (4 cm or greater) to stage IIIA disease, followed by chemotherapy when indicated.
“Some patients have very small tumors and no lymph nodes involved and do not need any further treatment after surgery, but these patients were not included in the PEARLS study (KEYNOTE-091),” Mary O’Brien, MD, FRCP, consultant medical oncologist in the department of oncology at The Royal Marsden Hospital in the U.K., told Healio. “The KEYNOTE-091 study recruited patients after surgery who still have about a 50% chance of recurrence within 5 years. A course of chemotherapy decreases this risk [for] recurrence and, if a patient is fit and accepting of this treatment, this is given. However, there remains a significant risk [for] relapse.”
Researchers randomly assigned 1,177 patients to 200 mg pembrolizumab (n = 590) or placebo (n = 587) via IV every 3 weeks for up to 18 doses. The treatment groups had similar baseline characteristics, including number of patients with tumor proportion score (TPS) of 50% or greater (n = 168 pembrolizumab, n = 165 placebo).
DFS in the overall population and among those with a PD-L1 TPS of 50% or greater served as dual primary endpoints. Secondary endpoints included DFS among patients with a PD-L1 TPS of 1% or greater, OS and safety.
Median time from random assignment to data cutoff on Sept. 20 for the second interim analysis was 35.6 months (range, 16.5-68).
Results
Among the overall population, patients in the pembrolizumab group had a statistically significant 24% reduction in risk for disease recurrence or death compared with those in the placebo group (median, 53.6 months vs. 42 months; HR = 0.76; 95% CI, 0.63-0.91).
Researchers reported improvement in DFS with pembrolizumab vs. placebo among patients with a PD-L1 TPS of 50% or greater; however, the results did not cross the prespecified boundary for statistical significance (median not reached in either group; HR = 0.82; 95% CI, 0.57-1.18). They also noted a favorable trend in OS regardless of PD-L1 expression, although with only 209 events, statistical significance had not been reached (18-month rate, 91.7% vs. 91.3%; HR = 0.87; 95% CI, 0.67-1.15).
“I was surprised and impressed that all PD-L1 subgroups did show a benefit, and these results were also impressive in stage IB disease,” O’Brien said. “Previously, chemotherapy demonstrated its greatest benefit in stages II and III.”
The pembrolizumab group had higher rates of grade 3 or higher adverse events (34.1% vs. 25.8%), adverse events that led to treatment discontinuation (19.8% vs. 5.9%) and treatment-related deaths (0.7% vs. 0) than the placebo group.
Implications, next steps
Evaluation of DFS among the PD-L1-defined subgroups and OS will continue, according to researchers.
“Hopefully, this drug will be approved and available to all patients as in the trial entry criteria, improving the cure rate from surgery in early-stage NSCLC,” O’Brien told Healio.
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Paz-Ares L, et al. Abstract VP3-2022. Presented at: ESMO Virtual Plenary; March 17, 2022.
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