Main Session
Sep
29
PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care
3525 - Association of Primary Tumor NF1 Mutations With Pathologic Complete Response After Neoadjuvant Immunotherapy in Stage I-III NSCLC
Presenter(s)
Victor Lee, MD, BS - Yale New Haven Hospital, Middletown, CT
V. Lee1, S. Hossain2, A. Lobo3, N. Rahman4, J. A. Paredes Mogica5, P. Oh1, T. J. Hayman1, A. A. Patel6, and H. S. M. Park1; 1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 2Center for Outcomes Research and Evaluation (CORE), New Haven, CT, 3Bridgeport Hospital, Bridgeport, CT, 4Bridgeport Hospital, Bridgeport Hospital, CT, 5Yale New Haven Health, New Haven, CT, 6Yale University School of Medicine, New Haven, CT
Purpose/Objective(s):
Neoadjuvant immunotherapy improves pathologic response rates in resectable stage I–III non–small cell lung cancer (NSCLC), yet predictive genomic biomarkers remain incompletely defined. Given the biologic role of NF1 as a negative regulator of RAS/MAPK signaling and its potential association with increased tumor immunogenicity, we hypothesized that NF1-mutated tumors would demonstrate higher rates of pathologic complete response (pCR) following neoadjuvant immunotherapy. We evaluated associations between primary tumor genomic alterations and pCR in a real-world clinicogenomic cohort.Materials/Methods:
Patients with stage I–III NSCLC treated with neoadjuvant immunotherapy followed by surgery were included from the Flatiron Health-Foundation Medicine Clinico-Genomic Database. Primary tumor genomic alterations were assessed using comprehensive genomic profiling. The primary endpoint was pCR. Univariate logistic regression was performed to evaluate associations between individual gene mutations and pCR. Multivariable analysis was not performed due to limited sample size and event counts. Statistical analyses were conducted in Python 3.7.Results:
Thirty-two patients met inclusion criteria; 5 (15.6%) achieved pCR and 27 (84.4%) did not. NF1 mutations were present in 3 of 5 patients (60%) who achieved pCR compared with 4 of 27 patients (14.8%) who did not achieve pCR. On univariate logistic regression, NF1 mutation was associated with increased likelihood of pCR (OR 8.62; 95% CI 1.08–69.08; p=0.042).Conclusion:
In this small real-world clinicogenomic cohort, primary tumor NF1 mutations were associated with higher odds of pCR following neoadjuvant immunotherapy. However, given the limited sample size, small number of events, and wide confidence interval, these findings should be considered hypothesis-generating. While NF1 represents a biologically plausible predictive biomarker, validation in larger prospective cohorts is necessary before clinical application. These results may inform future biomarker-stratified trial design rather than immediate treatment selection decisions.