Exploring the evolving therapeutic landscape of stage IV lung squamous cell carcinoma: A 13-year single center experience.

e20569 Background: Several seminal trials have reshaped the standard treatment of stage IV lung squamous cell carcinoma (SCC) over the last decade and introduced immunotherapy as an integral component to novel regimens. In our retrospective analysis, we aim to study the impact of front-line new regimens compared to conventional chemotherapeutic regimens on overall survival (OS) and progression free survival (PFS) in the largest and longest follow-up real world experience. Methods: Our study included adult patients (≥18 years) with de novo stage IV lung SCC at diagnosis at Cleveland Clinic Foundation (CCF) from 1/2010-12/2022. We excluded patients who did not receive therapy. Baseline variable such as sex, age, smoking history, performance status, PDL-1 testing, and molecular testing were collected. Response to treatment was assessed using RECIST 1.1 response criteria. OS and PFS were calculated from time of initiation of first-line therapy. We used multivariable cox hazard regression (CPH) to adjust for confounding. We compared two groups: 1. immunotherapy (IT), chemotherapy–immunotherapy (chemo-IT) and targeted therapies, which were grouped together as “modern therapies” and 2. conventional chemotherapy group (CTX). Results: We included 335 patients with stage IV SCC at diagnosis at CCF. Median age was 68 years (IQR: 62-75), 67% male, 84% white and 6.6% never smokers. Treatments administered included CTX (203, 61%), IT (60, 18%), Chemo-IT (68, 20%), and targeted therapy (4, 1.2%). The most common CTX were carboplatin + gemcitabine (93, 46%) and carboplatin + paclitaxel (N= 65, 32%), IT was pembrolizumab (N= 50, 83%), chemo-IT was carboplatin + paclitaxel + pembrolizumab (N = 51, 75%). For the whole cohort, the response rate was ~50%. With a median follow-up of 27.5 months, the 1-year and 2-year OS were 29% (95% CI 24-36) and 12% (95% CI 8.4-18) for CTX and 43% (95% CI 35-52) and 26% (95% CI 19-34) for modern therapies. On multivariable CPH, modern therapies were associated with increased OS compared to CTX regimens (HR 0.76, 95% CI 0.60-0.97, p = 0.025). PFS was also improved in modern regimens (p<0.05). Increasing age (as a continuous variable) was significantly associated with decreased OS (HR 1.02, 95% CI 1.01-1.03, P=0.003). Moreover, increasing neutrophils predicted higher mortality (HR 1.03, 95% CI 1.00-1.07, P= 0.041). Using multivariable CPH model, there was no difference in OS between carboplatin + paclitaxel and carboplatin + gemcitabine (HR 0.79, 95% CI 0.56-1.11, p=0.2). Conclusions: In the largest retrospective analysis of stage IV lung SCC that compares the front-line modern therapeutic modalities with the CTX, we confirmed the benefit of IT/targeted therapy on OS and PFS, using real world evidence. Long-term survival outcomes of stage IV SCC remain poor and further research is warranted to improve outcomes.