A Prospective Observational Study of Proton Stereotactic Body Radiation Therapy and Immunotherapy for Recurrent Metastatic Head and Neck Cancer: Initial Report of MC ROR1771 Survival Analysis and Toxicity

Abstract

<h3>Purpose/Objective(s)</h3> Patients with recurrent head and neck squamous cell carcinoma (HNSCC) after previous platinum-based chemotherapy have a median survival of 6 months or less. CheckMate 141 demonstrated that nivolumab administration to this patient population led to a median 7.5-month survival vs. 5.1-months with standard therapy, with 36% 1-year overall survival. The effect of radiotherapy on tumor immunogenicity when combined with immunotherapy has been an area of interest in immuno-oncology. However, proton therapy's role in this space is not well understood. MC ROR1771 was designed as a multisite prospective observational study to evaluate the addition of stereotactic body proton therapy (SBPT) to nivolumab in a platinum-refractory population. <h3>Materials/Methods</h3> Patients with metastatic histologically confirmed HNSCC from any primary site were eligible. Two cycles of nivolumab every other week were followed by SBPT to 1-2 target lesion(s). Maintenance nivolumab continued every other week with follow-up for progression and treatment toxicity. Subsequent oligoprogression was treated with stereotactic body radiotherapy or SBPT as indicated. Objective criteria included target lesion response rate, overall survival, progression-free survival, time to distant metastasis, toxicity, and evaluation of potential predictive biomarkers. Survival analysis was conducted using the Kaplan-Meier method in statistical software. The focus of this report was survival and toxicity analyses. <h3>Results</h3> 15 patients enrolled with 13 receiving SBPT, after which one treated patient withdrew. Of the remaining twelve, 3 had laryngeal primary, 1 nasopharyngeal, and 8 oropharyngeal. 4 patients underwent one round of prior chemotherapy before enrollment, 3 patients two rounds, and 5 patients three rounds: 10 received concurrent chemoradiation in first line (5 definitive, 5 adjuvant), with 1 receiving neoadjuvant chemotherapy prior to chemoradiation, and one presenting with metastatic disease. SBPT dosing ranged from 35-50 Gy. From initiation of nivolumab, median overall survival was 12.5 months (1-year overall survival 67%), with median progression free survival of 4.5 months. Two patients presented with baseline grade 3 cancer pain; no ≥grade 3 toxicity specific to nivolumab nor SBPT was reported. One patient is still alive at 40 months from initiation of nivolumab. <h3>Conclusion</h3> In this highly pretreated population, overall and progression-free survival compare favorably with CheckMate 141, suggesting that SBPT co-treatment may be beneficial in this population. No ≥grade 3 toxicity occurred with nivolumab nor SBPT. Biochemical analysis and correlation with delineated local, regional, and distant radiographic response are forthcoming. Further prospective evaluation of combination SBPT and immunotherapy is needed.