Response to neoadjuvant chemoimmunotherapy in EGFR- or ALK-mutated non-small cell lung cancer.

Abstract

8054 Background: The role of immunotherapy in non-metastatic EGFR-and ALK-mutated lung cancer is limited, in part because of a lack of efficacy, and partly because of the high response rates to mutation-targeting therapies. However, a subset of immunotherapy-responsive lung cancers may be cured, but only if immunotherapy is included in the treatment strategy. Therefore, a blanket exclusion of all EGFR-and ALK-mutated patients from immunotherapy may restrict a small subset of patients from a potentially curative option. Our objective was to determine the rate of highly immunotherapy-responsive tumors harboring EGFR and ALK mutations. Methods: Adult patients in the NCDB with clinical stage I-III NSCLC diagnosed between 2021 and 2023 and treated with neoadjuvant chemoimmunotherapy followed by definitive surgery (wedge resection, segmentectomy, lobectomy, or pneumonectomy) were included. Outcomes were pathologic complete response (pCR, defined as pathologic T0N0 after definitive resection) and nodal downstaging (pathologic N lower than clinical N stage). Covariates of interest for univariate analyses and multivariable logistic regression were year of diagnosis, region, age, sex, race/ethnicity, insurance, Charlson-Deyo score, clinical stage, and receipt of neoadjuvant immunotherapy. Results: Of 3,107 eligible patients, 1,133 (36.4%) were tested for EGFR and/or ALK mutations. Overall, 132 (11.7%) patients were found to have mutation(s) in EFGR (99 patients), ALK (27 patients) or both (6 patients). Among those with cN1-3 tumors, nodal downstaging was observed in 57.4% of patients with EGFR/ALK mutations and 74.2% of wild-type patients (p<0.001). The rate of pCR was 16.7% in EGFR-/ALK-mutated patients, and 30.9% in wild-type patients (p<0.001). Higher tumor grade was associated with significantly higher odds of pCR in EGFR/ALK wild-type patients (OR 2.448, 95% CI 1.58-3.89, p<0.001), but not in EGFR-/ALK-mutated patients (OR 2.63, 95% CI 0.37-18.74, p=0.33). Conclusions: While a less common practice, neoadjuvant chemoimmunotherapy in patients with EGFR-/ALK-mutated NSCLC demonstrated a pCR rate of 17% in this large real-world NCDB cohort. Further study on the role of neoadjuvant chemoimmunotherapy for this population is indicated given the potential for curative response, particularly in patients with mutations lacking effective targeted therapy. Mutation Type EGFR/ALKwild-type (n=1152) EGFR-/ALK- mutated (n=132) p EGFR (n=105) Exon 18, 19, 20, and/or 21 54 (51.4%) Other exon 11 (10.5%) ALK (n=33) EML4-ALK, KIF5B-ALK, TFG-ALK, and/or KLC1-ALK 13 (39.4%) Other rearrangement 10 (30.3%) Response Outcomes Nodal Downstaging (pN < cN), cN1-3 patients only 482/650 (74.2%) 50/87 (57.4%) <0.001 Complete Pathologic Response (ypT0N0) 356 (94.2%) 22 (16.7%) <0.001