Abstract 1312P
Background
Sequential use of chemotherapy followed by immunotherapy (CT-IO) versus (vs) the reverse sequence (Sq), IO-CT, are both standard therapeutic approaches in advanced Non-Small Cell Lung Cancer (NSCLC) patients (pts). In KEYNOTE-024 trial, the IO-CT Sq demonstrated its superiority in terms of progression free survival after the second line (2L) of therapy (PFS2) and overall survival (OS) in PD-L1 ≥ 50% NSCLC. However, the best Sq in PD-L1 low (<50%) NSCLC pts is still undefined.
Methods
We conducted an exploratory analysis to compare the unplanned Sq of CT-IO vs IO-CT in pts with locally advanced or metastatic PD-L1 low NSCLC, treated at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Pts enrolled in the phase II monocentric PEOPLE trial (NCT03447678) were included in the analysis. Primary endpoint was PFS2, defined as the time from start of first line (1L) to disease progression after the 2L of treatment or death, whichever occurred first. OS was also explored. Analyses were performed using the Kaplan-Meier method and Cox proportional-hazard models. Multivariate analyses were performed to control for potential confounders. Data cutoff was 12th Feb 2020.
Results
Among 172 pts who started 1L between June 2012 and December 2019, 110 (64%) received CT-IO and 62 (36%) IO-CT. Of these latter, 14 (8% of all pts) were still receiving 1L IO at time of data analysis. At a median follow-up of 39.0 months (mos), the CT-IO Sq was associated with significantly longer PFS2 [11.7 vs 6.7 mos, HR 0.65 (95% 0.45 - 0.91), p=0.01] and non-significantly longer OS [15.3 vs 12.7 mos, HR 0.85 (95% CI 0.57-1.29), p=0.46]. Multivariate analysis confirmed longer PFS2 [HR 0.63 (95% CI 0.41 - 0.97), p=0.04] for CT-IO Sq, irrespectively of PD-L1 status (0 vs 1-49%), ECOG PS, tumor histology and smoking status. A similar non-significant trend [HR 0.87 (95% 0.53 - 1.41), p=0.6] for OS was observed.
Conclusions
In PD-L1 low NSCLC, CT-IO Sq is associated with longer PFS2, irrespectively of PD-L1 status. In KEYNOTE-189 trial, 1L concurrent IO+CT showed a greater benefit on PFS2 and OS compared to sequential CT-IO, irrespective of PD-L1 expression. Therefore, our data warrant further investigation, especially for PD-L1 low NSCLC pts not suitable for concurrent 1L IO+CT.
Clinical trial identification
NCT03447678, 1st May 2021.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Proto: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD. D. Signorelli: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb. F. de Braud: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): F. Hoffmann-La Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ignyta; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp and Dohme; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Serono; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer. M.C. Garassino: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD International GmbH; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim Italia S.p.A.; Honoraria (self), Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Ignyta; Honoraria (self), Research grant/Funding (institution): Incyte; Honoraria (self), Research grant/Funding (institution): Inivata; Honoraria (self), Research grant/Funding (institution): MedImmune; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Tiziana; Research grant/Funding (institution): Foundation Medicine; Research grant/Funding (institution): AIRC; Research grant/Funding (institution): AIFA; Research grant/Funding (institution): Italian Moh; Research grant/Funding (institution): TRANSCAN. G. Lo Russo: Honoraria (self): Eli Lilly; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.