Pembrolizumab in performance status 2 patients with non-small cell lung cancer (NSCLC): Results of the PePS2 trial

Abstract

Background: Many patients with advanced NSCLC present with a performance status (PS) of 2. All published immunotherapy data in NSCLC is in PS0-1 patients whilst its safety and activity in this important patient group is unknown. Methods: Between 4/1/2017 and 13/2/2018 the trial recruited 62 PS2 NSCLC patients. PS was assessed by the registering physician on several occasions prior to trial entry to ensure a bona fide PS2 population. Components of the ECOG PS2 criteria were incorporated into the exclusion/inclusion criteria. Previous therapy and PD-L1 status were recorded at baseline. Co-primary outcomes were: i) durable clinical benefit (DCB) defined as complete or partial response or stable disease at 18 weeks; and ii) toxicity defined as treatment-related dose delay or discontinuation due to adverse event (AE). Results: Median age 72 yrs (range 43-86), median follow-up 249 days. 60 patients commenced therapy and were evaluable. Co-primary outcomes, objective response rate (ORR) and progression-free survival (PFS) are presented below. 3/18 responders have relapsed, after 67, 201 and 287 days. 23 patients (38%) had grade 3/4 AE by CTCAE v4, 5 (8%) had such an event thought possibly related to pembrolizumab. Of potentially immune-related AEs: 7 patients (12%) reported acneiform/maculopapular rash (6 G1/ 2; 1 G3); 2 (3%) pruritus (1 each G1 and 2); 1 (2%) G3 vasculitis; 1 (2%) G3 pneumonitis; 1 (2%) G1 colitis; 1 (2%) G1 hyperthroidism; 4 (7%) hypothyroidism(1 G1, 3 G2); 1 (2%) G3 arthralgia. There were no obvious cases of hyperprogression. (Table Presented) Conclusions: This is the first prospective analysis of pembrolizumab in a rigorously assessed PS2 population. Pembrolizumab can be delivered safely to such patients providing levels of activity at least equivalent to a PS0-1 population. The trial demonstrates that pembrolizumab is a safe, effective therapy for this difficult to treat NSCLC population.