medwireNews: Patients with advanced non-small-cell lung cancer (NSCLC) and an ECOG performance status (PS)2 derive durable clinical benefit from pembrolizumab with acceptable toxicity, suggest findings from the phase 2 PePS2 trial published in The Lancet Respiratory Medicine.
In an accompanying comment, Joao Alessi and Mark Awad, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, emphasize the importance of this study, saying “[o]ur understanding of the safety and efficacy of immune checkpoint inhibitors in this population is quite limited.”
They add: “With the large numbers of patients who have an impaired PS at the time of their initial lung cancer diagnosis, PePS2 and other studies dedicated to the inclusion of this historically trial-ineligible population will hopefully expand immunotherapy treatment options and lead to meaningful improvements in their lives.”
After a median 10 months of follow-up, 38% of the 24 patients given first-line pembrolizumab 200 mg every 3 weeks had a durable clinical benefit (DCB), defined as a complete or partial response or stable disease lasting until at least the second computed tomography evaluation at week 18.
Among the 36 patients who received second- or later-line pembrolizumab at the same dose, 36% achieved a DCB.
Gary Middleton (University of Birmingham, UK) and fellow researchers found the benefit of pembrolizumab to be more pronounced in those with a high PD-L1 tumor proportion score (TPS); DCB rates rose from 22% for patients with a TPS below 1% (n=27) to 47% for those with a TPS of 1–49% (n=15), and 53% for those with a score of at least 50% (n=15).
The results were similar in a model stratified by line of therapy, with, for instance, estimated DCB rates for first-line pembrolizumab of 18.2% versus 44.6% among patients with a TPS below 1% and at least 50%, respectively, and corresponding rates of 24.0% and 53.7% for pembrolizumab given in subsequent lines.
Middleton and team note: “Efficacy outcomes are at least similar to those obtained in patients of PS0–1 given second-line pembrolizumab.”
And they add that there was “no obvious increase in the risk of immune related or other toxicities, or of hyperprogression.”
In all, 73% of patients had a grade 3 or higher adverse event (AE). Twelve of these events occurred in nine (15%) patients and were potentially related to pembrolizumab. The most common grade 3 or worse immune-related AEs were rash and hypothyroidism, while dyspnea, hyponatremia, and anorexia were the most common non-immune-related AEs of these grades.
Notably, there were no grade 5 treatment-related AEs or early deaths attributed to hyperprogression, and only 10% of patients discontinued due to toxicity, say the researchers.
They therefore suggest that “patients of PS2 with a TPS of 50% or greater could be considered for first-line pembrolizumab monotherapy,” adding that the PD-1 inhibitor may also be “a valuable and well tolerated second-line treatment option in patients of PS2, many of whom previously were not offered second-line therapy.”
However, the team stresses that “the results need to be validated in other datasets where PS2 status is carefully ascribed.”
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Lancet Respir Med 2020; doi:10.1016/S2213-2600(20)30033-3
Lancet Respir Med 2020; doi:10.1016/S2213-2600(20)30107-7