Abstract 1058P
Background
Squamous cell carcinomas of the lung (LUSC) are heavily associated with a history of smoking. They occur uncommonly in non-smokers, suggesting unique behavior and response to therapy. Unlike their adenocarcinoma counterparts, driver oncogenes are rarely found. Given a general lack of response to immunotherapy in non-smokers with NSCLC as a whole, a better understanding of tumor biology is necessary.
Methods
We conducted a review of all non-smoker patients with metastatic LUSC treated at the Princess Margaret Cancer Centre between 2013 and 2021. Patients with lymphoepithelial carcinomas, now also classified as LUSC were included. All information from tissue or plasma next generation sequencing (NGS) were reviewed. Treatment outcomes and survival were evaluated.
Results
We identified 37 non-smoker patients with LUSC. Median age of diagnosis was young, 63 years (34-80) and 51% were female. 58% of patients had a positive family history and 24% a personal history of second malignancy. Testing for human herpes virus (HHV) infection detected EBV in 7/15 and HPV in 2/11 patients. 5 patients had EGFR mutations. Aberrations in DNA damage repair (DDR) genes were found in 29% of patients (n=21) and included oncogenic mutations in MMR, BAP1 and FANC. PD-L1 (n=28) scored ≥50% in 54% of patients. Patients who received treatment with PD1 inhibitors (n=29), had an ORR 34%; and a median PFS 8.9 months (4.0-14.8), that appeared longer in HHV infections 10.0 (1.2-NR) or DDR gene mutations 18.3 (8.9-NR). A median of 2 lines of systemic therapy were given with a median OS of 23.0 months (9.0-43.0) in the whole cohort and 35.4 months (13.3-NR) in HHV infections. All patients with DDR gene mutations, median follow-up 18 months, remain alive at the time analysis.
Conclusions
Non-smokers with metastatic LUSC had a surprisingly good survival, which may, in part, be attributed to mutations in DDR genes. A strong family and personal history of second malignancies were observed. Though testing is not routinely done, EBV and HPV infections may play a role in tumorigenesis. An understanding of how these factors may impact the tumor immune microenvironment and subsequent response to treatment will be crucial in developing new therapies for this unique group of patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Lau: Financial Interests, Personal, Other, Honoraria: AstraZeneca. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Lilly, MSD, Pfizer, Roche, Takeda. A. Sacher: Financial Interests, Institutional, Invited Speaker: Genentech-Roche, BMS, AstraZeneca, Amgen, Iovance, CRISPR Therapeutics, Merck, Pfizer, GSK, Spectrum, Lilly. All other authors have declared no conflicts of interest.