1301P - A prognostic clinical and circulating biomarker model to identify futile chemo-radiotherapy (CRT) in stage III NSCLC

Background

CRT followed by adjuvant Durvalumab (D) is standard of care for fit patients (pts) with unresectable stage III NSCLC. However, most pts will not benefit from the CRT part of the treatment. We aimed to build a prognostic model to identify pts who may not benefit from CRT without D.

Methods

Pts with stage III NSCLC treated with curative intent CRT (platinum-doubled and chest RT to a dose of 60-66 Gy) were identified from the prospective biobank project (2003-2019; NCT01084785). No pts received immunotherapy or targeted agents, neither in the primary treatment, nor for recurrence. Clinical parameters included age, sex, performance status (PS), stage (UICC 8), BMI; circulating biomarkers were GM-CSF, IFNα2a, IFNy, IL-10, IL-12p70, IL-1β, IL-2, IL-6, IL-8, TNF-α, IFNβ, IL-1α, IP10, MCP1, PD-L1. Cut-off points were based on maximum Log-Rank statistic (with correction for multiple testing). Overall survival (OS) was calculated from start of RT. Significance level alpha was set at 0.05.

Results

342 pts were included: mean age 64.7 ± 9.4 yrs; 62.3 % male; PS 0: 36.3 %, 1: 50.8 %, 2 or more: 12.9 %; stage: IIIA: 42.7 %; IIIB: 45.0 %, IIIC: 12.3 %. Median follow-up was >10 years. Median OS was 1.8 years (95 % CI 1.46-2.20), the 1-, 2- and 5-year OS 65.8 %, 48.5 % and 27.5 %. In multivariate analysis, higher age (p=0.003), male gender (p=0.043), PS 2 or higher (p=0.036), stage IIIB (p=0.003) or stage IIIC (p<0.001), higher IL6 (p<0.001) and higher circulating PD-L1 (p=0.001) were significant for poorer OS. The best cut-offs for IL-6 and PD-L1 were 3.39 pg/ml and 155.52 pg/ml, respectively. The multivariate prognostic model had an AUC = 0.78 (95 % CI 0.73-0.84) for 1-year OS and 0.76 (0.71-0.81) for 2-year OS. Pts in the best prognostic group (below threshold for IL6 and PD-L1; 34.4 % of total) had a median OS of 44 months, in the intermediate group (above threshold for one biomarker; 41.8 % of total) a median OS of 20 months and in the worst group (both markers above threshold; 23.6 % of total) a median OS of 8 months.

Conclusions

This easy to apply multivariate model for OS, which includes IL6 and circulating PD-L1, may identify pts with a poor OS after standard CRT without immunotherapy. These pts may benefit from alternative treatments without platinum-based chemotherapy and RT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dirk De Ruysscher.

Funding

Maastro Cancer Foundation.

Disclosure

All authors have declared no conflicts of interest.