1346P - A population-level prognostic score model for early acquired resistance to frontline anti-PD-(L)1 therapy in metastatic non-small cell lung cancer (NSCLC)

Background

Acquired resistance (AR) to PD-(L)1 blockade is a common clinical challenge. We aimed to develop an easy-to-apply prognostic score model to identify metastatic NSCLC population at higher risk of AR when treated with frontline anti-PD-(L)1 plus platinum-based chemotherapy (1L PD1 combo).

Methods

This retrospective study analyzed curated electronic health record data from COTA’s US multi-center NSCLC database. The inclusion criteria were as follows: metastatic NSCLC diagnosed during 2015-2023, age 18+, no ALK or EGFR mutations, presented with real-world (rw) complete response or partial response per physician assessment (rwCR/PR) during 1L PD1 combo treatment. We assessed the association between previously reported pre-treatment prognostic clinical variables and progression free survival (rwPFS) from the time of initial response (rwR) using Cox regression; prognostic scores were guided by regression coefficients. Patients were classified into poor- (total score in top tertile) and good-prognosis (total score below top tertile). rwPFS and OS by risk group were assessed with Kaplan-Meier curves and unadjusted Cox regression.

Results

We included 446 responders (median time to rwR 2.2 months; 8 rwCR, 438 rwPR) to 1L PD1 combo (median age 67; 54% male; 72% non-squamous; 53% PD-L1≥1%; 7% ECOG = 2+). Using the proposed prognostic scoring system (Table), the total score ranged from 0 to 9. The hazards for rwPFS and rwOS were significantly higher (both p<0.0001, median rwPFS 5.9 vs 9.7 months, median rwOS 15.3 vs 34.3 months) in the poor- (total score 3+, n=182) compared to the good-prognosis group (total score 0-2, n=264).

Conclusions

The proposed prognostic score model with 8 clinical variables may facilitate identification of patient subsets at higher risk of progression on 1L PD1 therapy following initial response, and guide future updates in the management of metastatic NSCLC. Table: 1346P

rwPFS and rwOS (months) from the time of initial response (rwCR/PR) among patients with good- vs poor-prognosis

∗Score assignment: 0 point: non-squamous or not specified, PD-L1≥1%, BMI

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Johnson and Johnson.

Funding

Johnson and Johnson.

Disclosure

J.C. Murray: Financial Interests, Personal, Other, Consulting: Janssen, Johnson & Johnson, NCODA; Financial Interests, Personal, Advisory Board: MJH Life Sciences, Cadence Communications & Research; Financial Interests, Personal, Other, Travel & Accommodations: Caris Life Sciences; Financial Interests, Personal, Other, Advising: Curio Science; Financial Interests, Personal, Invited Speaker: ION Oncology Practice Network, prIME; Financial Interests, Personal, Stocks/Shares: Doximity; Financial Interests, Institutional, Coordinating PI: Merck. Q. Huang: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. C. Hu: Financial Interests, Personal, Speaker, Consultant, Advisor: Johnson and Johnson, Belay Diagnostics; Financial Interests, Personal, Funding: NIH, RTOG Foundation. E. Curran, C. Wong, L. Glatz, T. Wang, A. Hasan: Financial Interests, Personal, Financially compensated role, Employment: Johnson and Johnson. L. Villaruz: Financial Interests, Personal, Advisory Board: Sanofi, Gilead, Johnson and Johnson, EMD Serono, Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Local PI: Regeneron, GSK, BioAtla, BeiGene, Fujifilm, Amgen, Boehringer Ingelheim, Merck; Financial Interests, Institutional, Coordinating PI: Genentech. A. Schoenfeld: Financial Interests, Personal, Other, Consulting: Johnson and Johnson, KSQ Therapeutics, Perceptive Advisors, Legend Biotech, Iovance Biotherapeutics, Oppenheimer and Co; Financial Interests, Personal, Advisory Board: BMS, Enara Bio, Umoja Biopharma, Prelude Therapeutics, Immunocore, Amgen, Lyell ImmunoPharma, Heat Biologics; Financial Interests, Personal and Institutional, Steering Committee Member: Merck; Financial Interests, Institutional, Steering Committee Member: Iovance Biotherapeutics; Financial Interests, Institutional, Local PI: GSK, Achilles Therapeutics, BMS; Financial Interests, Local PI: Synthekine; Financial Interests, Institutional, Coordinating PI: Obsidian; Non-Financial Interests, Principal Investigator: GSK, Achilles Therapeutics, Iovance Therapeutics, BMS, Merck, PACT Pharma.