Real-world treatment patterns and overall survival in recurrent/metastatic head and neck squamous cell carcinoma following treatment with immune checkpoint inhibitor and platinum-based chemotherapy.

6038 Background: Treatments for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) include immune checkpoint inhibitors (ICI) and/or platinum-based chemotherapy, yet most patients (pts) will experience disease progression, with poor survival and limited therapeutic options in later-line settings. Real-world evidence in R/M HNSCC after ICI and platinum-based chemotherapy is limited. We characterize real-world treatments and survival outcomes in pts with heavily pretreated R/M HNSCC. Methods: This retrospective analysis used electronic medical records from the US Flatiron Health Advanced EDM (71% community centers, 22% academic centers, 7% both). Study period was 1 Jan 2015 to 31 Mar 2025 (date of data cutoff). All identified pts had R/M HNSCC and had received prior PD-1 inhibitor and platinum-based chemotherapy. Demographics, baseline disease characteristics, and treatment patterns were analyzed descriptively. Kaplan-Meier method was used to evaluate real-world overall survival (rwOS), defined as time from index date (first date of treatment after PD-1 inhibitor and platinum-based chemotherapy) until date of recorded death. Subgroups by HPV-unrelated (oral cavity, larynx, hypopharynx, HPV-negative oropharyngeal) and HPV-related (HPV-positive oropharyngeal) HNSCC were evaluated. Results: In total, 2105 pts with R/M HNSCC were identified from the Flatiron database as previously treated with PD-1 inhibitor and platinum-based chemotherapy. There were 1271 pts who did not receive any subsequent treatment, while 834 pts received an index line of therapy after PD-1 inhibitor and platinum-based chemotherapy and were eligible for analysis. Among those eligible, primary tumor site distribution was 55% oropharynx (81% HPV-positive / 19% HPV-negative), 21% larynx, 18% oral cavity, and 6% hypopharynx. Most pts had an ECOG score of 0 or 1 (77%). Most common regimens in the index line of therapy included chemotherapy, anti-EGFR, and/or PD-(L)1 agents. Among the 834 pts identified, rwOS was 7.8 months (95% CI, 7.0–8.4). There were 373 and 461 pts identified with HPV-related and HPV-unrelated disease, respectively. Median rwOS was significantly longer for the HPV-related vs HPV-unrelated group (9.3 months [95% CI, 8.2–10.9] vs 6.8 months [95% CI, 6.1–7.3]; HR, 0.85 [95% CI, 0.73–0.99]; P =0.036). The 6-month rwOS rate was 65% vs 55%, respectively. Of note, a substantial portion of pts died prior to receiving another line of therapy (39% for HPV-related and 49% for HPV-unrelated). Conclusions: Median rwOS is poor in R/M HNSCC following treatment with PD-1 inhibitor and platinum-based chemotherapy, and particularly poor for HPV-unrelated disease, with nearly half dying by 6 months. These results highlight the pressing need for innovative treatments to improve survival in R/M HNSCC.