1472P - Radiotherapy affects immunotherapy efficacy based on tumor mutation status in patients with metastatic NSCLC

Background

Radiotherapy (RT) may enhance the antitumoral response of immunotherapy (IO) in metastatic non-small-cell lung cancer (mNSCLC). However, whether tumor mutation status can affect RT’s effect on IO efficacy in mNSCLC is unknown.

Methods

We retrospectively studied all patients with mNSCLC who had tumor mutation profiles and were treated with IO at our institution from 2011 to 2022. Patients were excluded if they received targeted therapy, prior concurrent chemo-RT followed by durvalumab, or RT after IO discontinuation. We analyzed their demographic data, tumor mutation profiles, and compared progression-free survival (PFS) and overall survival (OS) between different subgroups. Kaplan-Meier method and log-rank test were used for survival analysis.

Results

A total of 171 patients were included. 66% received RT either prior to or during IO. Pembrolizumab was the most used IO agent (77%). IO was given mostly in the frontline setting (59%). Among 113 patients who received RT, ALK mutation (n=5) was associated with significantly shorter PFS of IO than those without ALK mutation (n= 108) (2m vs. 5.7m, p<0.0001). Similarly, MYC mutation (n=8) was associated with significantly shorter PFS than those without MYC mutation (n= 105) (3.3m vs. 6.2m, p=0.016). PFS of IO was not affected by the following genes: EGFR, KRAS, TP53, BRAF, ERBB2, BRAF, PIK3CA, TERT, and FGFR. For patients with tumors carrying STK11 mutation, those who received RT (n=21) had longer PFS of IO than those (n=8) without RT (6.5m vs. 2.8m, p=0.05). For patients with tumor carrying ARID1A mutation, those who received RT (n=11) had shorter PFS and OS of IO than those (n=7) without RT (PFS: 5m vs. 22.9m, p=0.08; OS: 16m vs. 28.1m, p=0.037, HR 0.28, 95% CI 0.08 – 0.9). No difference in the outcomes of IO between RT and no RT in the following mutations: EGFR, ERBB2, PIK3CA, KRAS, MET, and TP53.

Conclusions

In our real-world cohort, ALK and MYC mutations affect outcomes of IO in mNSCLC patients who received RT. RT is associated with better outcomes of IO in mNSCLC patients with STK11+, but poorer outcomes in those with ARID1A+. Our findings suggest certain gene mutations can affect radiotherapy’s effect on immunotherapy efficacy in mNSCLC. Further prospective studies are needed to verify these results.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

Y. Zhao: Financial Interests, Personal and Institutional, Research Funding: Zai Lab, PDS Biotechnology, Transgen, Mereo BioPharma, Mirati Therapeutics, Incyte, Pfizer, Alpine Immune Science , Merck & Co., Elucida Oncology. R. Manochakian: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Janssen, Alpha-2, Turning Point, Guardant health, Takeda, Novocure. Y. Lou: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca Pharmaceuticals, Janssen Pharmaceutical, Lilly Oncology, Turning Point Therapeutics, Oncohost; Financial Interests, Institutional, Advisory Board: Mirati Therapeutics ; Financial Interests, Personal and Institutional, Research Funding: Merck, Tolero Pharmaceuticals, AstraZeneca, Blueprint Medicines, Sun Pharma, Mirati Therapeutics, Genmab, EMD Serono, Jacobio Pharma, Topallian, Daiichi Sankyo. All other authors have declared no conflicts of interest.