Findings from the KEYNOTE-091 trial showed that patients with non–small cell lung cancer who were treated with pembrolizumab following complete resection and chemotherapy had a 24% decreased risk of recurrence compared with a control arm.
Adjuvant pembrolizumab (Keytruda) following complete resection demonstrated statistically significant and clinically meaningful improvements in disease-free survival (DFS) among patients with stage IB to IIIA non–small cell lung cancer, according to findings of the phase 3 EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study (NCT02504372) that were recently presented at the 2022 ESMO Plenary.
In an analysis of all study populations, regardless of PD-L1 expression, the median DFS was 53.6 months in the pembrolizumab group vs 42.0 months in the control group (HR, 0.76; 95% CI, 0.63-0.91; P = .0014). However, the DFS data did not reach the significance threshold among patients with a tumor proportion score (TPS) of at least 50% (median not reached in either arm; HR, 0.82; 95% CI, 0.57-1.18; P = .14).
Similarly, the significance threshold for overall survival (OS) was not reached in the all-comers population (HR, 0.87; 95% CI 0.67-1.15; P = .17); only 209 events were reported. The 18-month OS rate was 91.7% with pembrolizumab vs 91.3% with the control arm.
Moreover, the safety profile associated with the PD-1/PD-L1 inhibitor was consistent with previously reported profiles. Further analyses will seek to assess DFS and OS among the PD-L1–specific population.
“Even when [NSCLC] is early-stage and caught in time, only about 50% of patients are actually cured [post-surgery], which means [that for the remaining patients], the disease either comes back, or the disease was more advanced than was initially thought,” Mary O’Brien, PhD, a medical oncologists at the Royal Marsden in London, and professor of practice medical oncology at Imperial College London, said in an interview with Oncology Nursing News®. “These are the patients that are high risk…but this immunotherapy seems to do twice as much and decreases the risk of [recurrence] by about 24%. Ultimately, we are ‘nibbling’ away at this cancer and increasing the number of patients who are cured by their surgery.”
The randomized, triple-blind, phase 3 EORTC-1416-LCG/ETOP 8-15–PEARLS/KEYNOTE-091 study randomized 1177 patients with stage IB, II, or IIIA NSCLC to receive either pembrolizumab (n = 590) at 200 mg or placebo n = (587) every 3 weeks for 18 doses following complete resection (T ≥4 cm) and adjuvant chemotherapy, ad indicated per guidelines. Overall, the median number of doses that patients received was 17 doses in the pembrolizumab arm and 18 in the placebo arm.
Of note, 168 patients in the pembrolizumab arm and 165 patients in the placebo arm also had a TPS of at least 50%. The baseline characteristics were reportedly similar between the 2 arms and the median time from randomization to data cutoff was 35.6 months (range, 16.5-68.0).
The primary objective of the trial was DFS in both the all-comers and PD-L1 TPS 50% or higher populations. The secondary objectives included DFS in the TPS ≥1% population, OS in the all-comers, TPS at least 50% and at least 1% populations, and safety. The data recently reported at the 2022 ESMO Plenary were collected at the protocol-specified second interim analysis data cutoff in September 2021.
In terms of adverse events (AEs), 34.1% of patients in the investigational arm experienced a grade 3 or higher AE compared with 25.8% of patients in the placebo arm. Discontinuation because of severe grade AEs occurred in 19.8% vs 5.9% of patients in the 2 arms, respectively, and treatment-related fatal AEs occurred in 0.7% vs 0% of patients in the 2 arms.
O’Brien noted that investigators have yet to determine the extended benefit of this treatment, but the current data are promising.
“Would 2 years [with pembrolizumab] do more [in terms of benefit]? Would 2 years combined with another drug do even more?” she said. “The research going forward will be addressing all of these things; we have opened a whole new world now after surgery.”
She also acknowledged that, historically, clinical trials did not always assess patients post-surgery because approximately half of patients did not experience recurrence. However, research is now aimed to find a durable treatment plan for the remaining 50% of patients.
“We have got over that hurdle and we are focusing on the half that are not cured,” she said. “We can make a difference, so, we will be doing more trials in this spot. We will be asking all these questions.”
Paz-Ares L, O’Brien MER, Mauer M, et al. Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: randomized, triple-blind, phase 3 EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study. Ann Oncol. 2022;33(4):451-453. doi:10.1016/j.annonc.2022.02.224