Abstract 1328P
Background
It has not yet been established whether local consolidative therapy in addition to immune checkpoint inhibitors improve outcomes.
Methods
We queried the internal institutional database to identify EGFR/ALK wild type stage IV NSCLC patients treated with ICI alone or with chemotherapy. PD-L1 status was aggregated into PD-L1<1%; 1-49%; ³ 50%; or unknown. Stage IV subtype was defined based on TNM 8th, and M1c was divided based on central nervous system metastases (M1c+/-CNS). History of LCT with radiation or surgery was identified; comprehensive LCT (cLCT) was defined as LCT to all metastatic lesions. Outcome measures were defined as clinical progression free survival (PFS) or overall survival (OS), and their association with LCT was assessed via Cox Proportional Hazards model.
Results
1,176 patients were included in this study, 696 treated in the first-line setting. Outcomes varied by number and distribution of disease sites; PFS and OS were longest in patients with a single brain metastasis (n=35; mPFS=10.7 mo, mOS=46.6 mo), whereas patients with M1c did poorly with or without CNS metastases (mPFS=5.3 mo, mOS=20 mo). PD-L1³ 50% associated with marked PFS and OS benefit in patients with M1a or M1b disease (M1a mPFS=NR, p<0.001, mOS NR, p<0.001; M1b mPFS=28.2 mo, p=0.022; mOS=NR, p=0.015), whereas patients with M1c+CNS did poorly regardless of PD-L1 status (PFS p=0.096, OS p= 0.272). Of the patients with extrathoracic metastases, 663/943 (70%) had partial or cLCT. Patients with cLCT (n=352) had better mPFS (7.6 vs 4.9 mo, p=0.001) and mOS (26.5 vs 18.5 mo, p<0.001) compared to those with no/partial LCT (n=591). Subgroup analysis demonstrated that M1c+CNS patients (n=411) had improved PFS and OS with cLCT vs no/partial LCT (mPFS 6.4 vs 4.9 mo, p=0.008; mOS 25.3 vs 18.0 mo, p=0.001). When stratified by PD-L1, the difference remained significant among PD-L1=1-49% or PD-L1<1% patients; cLCT showed no benefit in PD-L1³ 50%.
Conclusions
In this population, cLCT was associated with improved PFS and OS, particularly in patients with CNS metastases. Patients with PD-L1³ 50% may not experience additive benefit from LCT beyond what is achieved with ICI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The University of Texas MD Anderson Lung Moon Shot Program and the MD Anderson Cancer Center Support Grant P30 CA016672.
Disclosure
S.J. Gandhi: Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Bristol Myers Squibb; Financial Interests, Personal, Funding: Millennium Pharmaceuticals. D.L. Gibbons: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Funding: Janssen; Financial Interests, Personal, Funding: Takeda; Financial Interests, Personal, Funding: Ribon Therapeutics; Financial Interests, Personal, Funding: Astellas; Financial Interests, Personal, Funding: Boehringer Ingelheim; Financial Interests, Personal, Funding: AstraZeneca. J.V. Heymach: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Kairos Venture Investments; Financial Interests, Personal, Advisory Board: BrightPath Therapeutics; Financial Interests, Personal, Advisory Board: Hengrui Therapeutics; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Foundation One Medicine; Financial Interests, Personal, Advisory Board: Spectrum; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Funding: NIH/NCI; Financial Interests, Personal, Funding: American Cancer Society; Financial Interests, Personal, Funding: Checkmate Pharmaceuticals; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Spectrum; Financial Interests, Personal, Royalties: Spectrum. J. Zhang: Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Funding: Johnson & Johnson; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: GenePlus-Beijing Institute; Financial Interests, Personal, Advisory Board: Innovent. N.I. Vokes: Financial Interests, Personal, Advisory Board: Sanofi. All other authors have declared no conflicts of interest.