Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Pembrolizumab, as assessed in the KEYNOTE-689 trial, demonstrated significant efficacy in improving event-free survival (EFS) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The KEYNOTE-689 study used pembrolizumab alone in perioperative settings, showing statistically significant EFS gains and trends towards higher overall survival (OS) with minimal delay in definitive treatment. However, the addition of chemotherapy to immunotherapy may enhance response rates and downstaging potential, albeit with increased toxicity and potential delays.
Our objective is to retrospectively analyze MD Anderson’s experience with chemo-immunotherapy in LA-HNSCC, focusing on imaging-based treatment response, survival outcomes, and the impact of chemotherapy on treatment feasibility.
Methods: This retrospective analysis included 52 patients with LA-HNSCC treated with combined chemotherapy and immunotherapy from 2019 to 2024. Key data collected included patient demographics, tumor characteristics, prior treatment history, and treatment regimens. Imaging-based response was assessed using RECIST criteria, with the primary outcome being the Objective Response Rate (ORR), including complete and partial responses. Secondary outcomes included EFS, calculated as the time from the first dose of therapy to progression, recurrence, or death, and overall survival (OS). PD-L1 expression was examined using the Combined Positive Score (CPS) to provide interpretative context, though these findings were not included in the results.
Results: Among the 52 patients, the average age was 65 years, with a predominance of male patients (73%, n=38). Tumor sites primarily involved the gingiva (29%, n=15), anterior tongue (25%, n=13), and floor of the mouth (13%, n=7). The majority of cases were recurrent tumors (82%), with the remainder being primary or second primary tumors, and 13% of tumors were treatment-naïve. The most commonly used chemo-immunotherapy regimen was carboplatin, docetaxel, and pembrolizumab, administered in 42% (n=22) of cases. ORR was achieved in 52% of patients, with 21% (n=11) reaching a complete response. Post-chemo-immunotherapy surgery was performed in 31% (n=16) of cases; notably, 14% of these surgeries were made feasible with R0 resection due to tumor downstaging from the chemo-immunotherapy regimen.
The mean EFS and OS for the entire cohort were 17.6 months and 23.6 months, respectively. Patients with an objective response (ORR) had a significantly longer EFS compared to non-responders (27.1 months vs. 15.1 months). Furthermore, among patients achieving a complete response, those who subsequently underwent surgery had an extended EFS of 39 months, suggesting potential benefits from multimodal therapy in this group.
Conclusion: The MD Anderson experience highlights the potential benefits of combining chemotherapy with immunotherapy in LA-HNSCC, aligning with the findings from KEYNOTE-689 on pembrolizumab. Our data suggest that chemo-immunotherapy may improve resectability and extend survival, particularly among patients who achieve a complete response and undergo surgery. However, the added toxicity and potential delays associated with chemotherapy warrant careful consideration. Further studies are needed to evaluate the long-term impact of adding chemotherapy to immunotherapy and to optimize patient selection for this aggressive approach.