The impact of regional lymph node depletion on response to anti-PD-1 therapy in recurrent and metastatic head and neck squamous cell carcinoma

Objective Cervical lymphadenectomy remains a central component of definitive treatment for primary head and neck squamous cell carcinoma (HNSCC). However, the impact of previous lymphadenectomy, and extent thereof, on anti-PD-1 response in patients who develop recurrent/metastatic (R/M) disease after definitive treatment remains unknown. Here, we evaluated the hypothesis that history of regional lymph node depletion is associated with decreased efficacy of anti-PD-1 therapy in patients who suffer R/M HNSCC after definitive treatment. Materials and Methods This was a single-institution, retrospective cohort study of 97 patients treated with anti-PD-1 mAb for R/M HNSCC. Impact of regional lymph node (LN) depletion (i.e., bilateral lymphadenectomy, five or more levels dissected, and/or 18 or more lymph nodes excised at any time prior to anti-PD-1 therapy) was examined as a predictor of R/M HNSCC disease control rate (DCR: SD, PR, or CR), progression-free survival (PFS) and overall survival (OS) with Kaplan-Meier method and multivariate models. Results Ninety-seven patients (median age 62 years, 72 % male, 76 % p16- HNSCC); 48 (50 %) patients had a history of regional LN depletion prior to anti-PD-1 therapy. Regional LN depletion was significantly associated with poorer DCR and PFS after anti-PD-1 alone and controlling for history of platinum chemotherapy failure (OR: 0.12 [0.02 – 0.66], p = 0.008 for DCR, HR: 1.89 [1.04 – 3.38], p = 0.04 for PFS). Conclusions In this retrospective, single-institution study of patients with R/M HNSCC, regional LN depletion was independently associated with lower DCR and PFS after anti-PD-1 therapy.