Outcomes and factors associated with first line chemoimmunotherapy (ChemoIO) or immunotherapy (IO) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

e18095 Background: IO alone or with chemotherapy, is standard first-line therapy for recurrent/metastatic HNSCC. This study investigates real-world outcomes and clinical factors associated with survival in patients (pts) receiving first-line chemoIO or IO alone. Methods: Pts with recurrent/metastatic HNSCC treated with first-line IO +/- chemotherapy between 2013-2024 were included in this IRB approved retrospective study. Nasopharyngeal and salivary gland cancers were excluded. Progression free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods and compared using log-rank test. Cox proportional hazards regression was used to identify factors associated with OS. Results: The cohort comprised 267 pts with median age 65 (range 28-98), and 215 (80.5%) male. Of these, 210 (78.7%) had distant metastatic disease and 102 (38.2%) were platinum refractory. Most received IO alone (215, 80.5%). Median follow up was 10 mos (0-121). Median PFS for the cohort was 4.3 mos, with longer PFS in pts receiving chemoIO (6.6 vs. 3.8 mos; p = 0.14). PD-L1 status was available for 181 (67.8%) of the pts. Median PFS stratified by PD-L1 was similar: 6.6 (CPS <1), 4.2 (CPS 1–19), and 5.6 mos (CPS ≥20; p = 0.04). Pts with bony disease had significantly worse PFS compared to those with either visceral disease alone or locoregional disease (mPFS 2.6 vs. 5.1 vs 6.6 mos; p<0.05). Median OS was longer in pts receiving chemoIO than IO alone; 13.9 vs. 10.0 mos (p = 0.06). Median OS stratified by PD-L1 was similar: 12.5 (CPS <1,); 12.8 (CPS 1–19), 14.2 mos (CPS ≥20) (p = 0.59). Pts with bony and visceral disease had significantly worse OS compared to those with visceral disease alone or locoregional disease (mOS 4.5 vs. 11.1 vs. 13.8 mos; p<0.05)Clinical factors associated with worse OS on UVA included platinum refractory at time of treatment start, HR 1.59, 95%CI 1.20-2.08; presence of bony and visceral disease compared to locoregional HR 1.64, 1.06-2.54 or visceral disease only HR 1.94, 1.34-2.81; extensive metastatic burden (≥6 metastases vs. ≤5 or locoregional disease) HR 1.46, 1.11-1.93; and higher platelets HR 1.01, 1.001-1.003 (p<0.05 for all). Higher KPS was associated with better OS [HR 0.96, 0.94-0.97. On multivariable analysis, lower KPS HR 1.05, 1.03–1.06, platinum-refractory disease HR 1.72, 1.28-2.33, higher baseline platelet count HR 1.002, 1.001–1.003, and extensive metastatic burden HR 1.52, 1.12-2.08 were independently associated with worse OS (p<0.05 for all). Conclusions: In this real-world cohort, first-line chemoIO or IO demonstrated outcomes consistent with KEYNOTE 048 with trends toward improved PFS and OS in chemoIO. Performance status and disease burden were key determinants of survival. Further studies are needed to refine biomarkers and pt selection for IO alone in recurrent/metastatic HNSCC.