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.
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).
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: 1384PD
|DCB (%)||ORR (%)||Median PFS months||Toxicity (%)|
|All (n = 60)||20 (33)||18 (30)||4.4||8 (13)|
|No (n = 9)||1 (11)||0 (0)||1.9||2 (22)|
|Yes (n = 50)||19 (38)||18 (36)||4.6||6 (12)|
|Missing (n = 1)||0 (0)||0 (0)||0 (0)|
|< 1% (n = 27)||6 (22)||5 (19)||3.3||4 (15)|
|1-49% (n = 15)||5 (33)||5 (33)||6.8||0 (0)|
|≥ 50% (n = 15)||8 (53)||7 (47)||8.5||3 (20)|
|Missing (n = 3)||1 (33)||1 (33)||1 (33)|
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.
Clinical trial identification
ISRCTN10047797, EudraCT: 2015-002241-55; NCT02733159.
Legal entity responsible for the study
University of Birmingham.
Merck Sharp & Dohme.
G. Middleton: Consultant: Roche, BI, BMS, MSD; Speaker’s bureau: MSD, BMS, Roche, Eli Lilly; Grant/Research support: Plexxikon, KAEL-GemVax, BMS, MSD; Honoraria: Roche, BI, BMS, MSD, Eli Lilly. K. Brock: Travel, accommodations, expenses: Merck Sharp & Dohme, Roche; Shares: AstraZeneca, GlaxoSmithKline. Y. Summers: Advisory board role: MSD, Pfizer, AZ, BMS, Takeda, Roche, BI. R. Shah: Advisory boards and speaker events: MSD. C. Ottensmeier: Consulting or advisory role: Bristol-Myers Squibb, Merck Sharp & Dohme, Immatics; Speakers' bureau: Bristol-Myers Squibb, Merck Sharp & Dohme, Roche; Research funding: Bristol-Myers Squibb, Verastem, Merck Sharp & Dohme, Inovio Pharmaceuticals, BioNTech AG, Serametrix, Touchlight Genetics, Delcath Systems; Travel, accommodations, expenses: Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Delcath Systems; Other relationship: Transgene. S. Popat: Honoraria: Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Consulting or advisory role: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, Bristol-Myers Squibb, MSD, Guardant Health, Abbvie; Research funding: Boehringer Ingelheim, Epizyme, Bristol-Myers Squibb, Clovis Oncology, Roche, Lilly, Takeda; Travel, accommodations, expenses: Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme. G. Barone: Consultant/advisor: Bristol-Myers Squibb; Travel and accommodation funding: Roche, Pfizer, Eli Lilly, Eisai. L. Billingham: Honoraria: Eli Lilly, Pfizer, Roche, Celgene, AstraZeneca. All other authors have declared no conflicts of interest.