Abstract 1370P
Background
In mNSCLC, PD-L1 expression is a biomarker for survival benefit with immune checkpoint inhibitor-based regimens (ICI). However, there are conflicting reports for its predictive value for chemotherapy alone which remains a treatment backbone in mNSCLC. We performed a meta-analysis to determine the role of PD-L1 expression in predicting response with platinum doublet chemotherapy.
Methods
We performed an electronic search to identify any first-line randomized trials that compared ICI, either as monotherapy or chemoimmunotherapy, against platinum-doublet chemotherapy. We extracted only data from the control chemotherapy arm. We performed pairwise comparisons of objective response rate (ORR) and 12-month progression-free survival rate (PFS12) according to PD-L1 expression. Data was pooled across trials using the inverse variance approach.
Results
Twelve trials were identified, involving 4031 patients with EGFR/ALK wild type tumors. The majority were males (N=2710, 67%), current/ex-smoker (N=3476, 86%), performance status 1 (N=2382, 59%), and had non-squamous histology (N=2712, 67%). Chemotherapy consisted of a cisplatin/carboplatin backbone with pemetrexed/gemcitabine/nab-paclitaxel. One trial included bevacizumab (N=400, 10%). PD-L1 expression status was available in 3717 (92%) patients of which 970 (26%) were PD-L1 negative (<1%), 1513 (41%) were PD-L1 low (1-49%), and 1234 (33%) were PDL1 high (≥50%). In pairwise comparisons, ORRs for PD-L1 high and low were 33.8% and 30.4% (risk difference [RD]=5%, P=0.01), PD-L1 high and negative were 35.6% and 32.0% (RD=7%, P=0.01), and PD-L1 low and negative were 34.5% and 32.0% (RD=4%, P=0.13), respectively. PFS12 rate was not significantly different across different PD-L1 subgroups.
Conclusions
High PD-L1 expression is associated with improved ORR with platinum doublet chemotherapy in mNSCLC. Our data suggests that this patient population is distinct, and high responses might reflect an adaptive tumor response to host immune pressure during chemotherapy. Further research is required to improve outcomes for low/negative PD-L1 tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C.K. Lee: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Takeda. C. Lewis: Advisory/Consultancy: AstraZeneca. T. John: Honoraria (self), Advisory/Consultancy: BristolMyerSquibb; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (institution): Specialised Therapeutics; Honoraria (institution): Pfizer; Honoraria (institution): Novartis. J.C-H. Yang: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Clovis Oncology; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical. All other authors have declared no conflicts of interest.