Efficacy of immune checkpoint inhibitors in lung sarcomatoid carcinoma: Data from a French multicentric cohort

Background: Immune checkpoint inhibitors (ICI) have improved outcomes of non-small cell lung cancer (NSCLC) patients. Previous findings showed that PD-L1 expression and immune-cell infiltration were high in sarcomatoid carcinoma (SC), a rare subset of NSCLC with a poor prognosis. This study sought to retrospectively assess the efficacy of ICI in SC. Methods: All consecutive patients (pts) with stage III or IV confirmed SC (reviewed by a specialized pathologist) receiving at least one dose of an ICI between 2011 and 2017 were enrolled. PD-L1 was considered positive if higher than 1%. Results: Forty-two centres participated to the study and 27 included 39 patients. At diagnosis, they were mostly men (81%), current (41%) or former (53.8%) smokers, with a median age of 63.2 years [36.8-84.6]. Performance status (PS) was 0-1 for 71.8% of them. Sixteen (48.8%) tumours were genotyped, and they were KRAS (38.5%), MET exon 14 (7.7%) or EGFR (2.6%) mutated. Almost all pts (94.9%) received previous platinum-based chemotherapy. ICI were administered as 1st / 2nd / ≥3rd-lines for 5.1% / 51.3% / 43.6%, respectively. Pts received by nivolumab (87.2%), pembrolizumab (7.7%) or atezolizumab (5.1%). Median duration of treatment was 4.5 months [0.5-24]. As best overall response, overall response rate (ORR) was 38.5%, disease control rate (DCR) 61.6% and progressive disease 30.8%. The main reason for ICI discontinuation was progression (69.2%), with a median PFS of 4.59 months [0.3-24.1] and a 1-year-PFS rate of 10.3% (4/39). Five (12.8%) pts died before the first radiologic evaluation under ICI with a median of 0.62 months [0.26-1.51]. Median survival was 20 months [1.7–61.7]. Eighteen pts (46.1%) received a subsequent line (chemotherapy (n = 15) or TKI (n = 3)) with 55.5% progressive disease, 27.8% stable disease and no partial response. PD-L1 status was assessed in 18 tumours (46.1%). In PDL1+ pts, ORR was 53.3% (8/15) and DCR was 66.7% (10/15). ORR and DCR were 33.3% (1/3) for both criteria in PDL1- pts. There was no difference in ORR (p = 0.73), DCR (p = 0.71), PFS (p = 0.34) and OS (p = 0.35) according to KRAS status. Conclusions: Our results suggest that SC pts may benefit from ICI. We are collecting tumour samples to assess the correlation between response and PD-L1 expression. Legal entity responsible for the study: Assistance Publique - Hôpitaux de Paris.. Funding: Has not received any funding. Disclosure: C. Domblides: Speaker: AstraZeneca; Travel: Pierre Fabre, AstraZeneca, Pfizer, Amgen, MSD, Roche; Research funding: AstraZeneca. J. Mazieres: Consulting or advisory role: AstraZeneca, Roche, BMS, MSD, Novartis, Pfizer; Research funding: AstraZeneca, Roche, BMS; Travel, accommodations, expenses: Roche, BMS, Novartis, Pfizer. S. Baldacci: Personal fees: Lilly, GSK, Pfizer, Roche for activities outside the written work. A.C. Toffart: Membership on advisory board: BMS, MSD; Speaker: AstraZeneca; Grant: Roche; Travel: BMS, Roche. C. Audigier Valette: Clinical trials as principal investigator: AstraZeneca, Boehringer Ingelheim, BMS, Novartis, Roche; Advisory board: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, MSD, Pfizer, Roche; Conferences and interventions: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, Pfizer, Roche. E. Giroux-Leprieur: Advisory board: AstraZeneca, Bristol-Myers Squibb, Novartis, Roche; Research grants: AstraZeneca, Bristol-Myers-Squibb, Roche. F. Guisier: Honoraria for consulting and advisory boards: BMS, MSD, Roche, AstraZeneca, Boehringer Ingelheim; Travel support: Chugai; Investigator in trials sponsored by: BMS, MSD, Roche, Takeda, Merrimack Pharmaceuticals, Janssen. M. Perol: Honoraria for Advisory boards and symposia: Bristol-Myers Squibb, Roche, Merck Sharp & Dohme (MSD), AstraZeneca. All other authors have declared no conflicts of interest.