Initial Experience With Palliative “QUAD-SHOT” Radiotherapy With Concurrent And Adjuvant PD-1 Inhibitor For Recurrent And/Or Metastatic Head And Neck Cancer

Abstract

To analyze our initial institutional experience of palliative “QUAD-SHOT” radiotherapy with concurrent and adjuvant PD-1 inhibitor for recurrent and/or metastatic head and neck cancers. Our hypothesis is that the addition of immunotherapy to palliative radiation is safe and will result in effective disease control. IRB approved retrospective analysis of fifteen patients (pts) with incurable loco-regionally recurrent and/or metastatic head and neck cancer. All pts received palliative radiation therapy (RT) with the “QUAD-SHOT” regimen (3.7 Gy twice daily over 2 consecutive days at 3-week intervals per cycle, total of 3 cycles) with concurrent and adjuvant PD-1 inhibitor (pembrolizumab q3w or nivolumab q2w) between 10/2016 – 10/2019. Pts continued on adjuvant immunotherapy until disease progression was documented. Tumor response was documented by radiologic imaging and physical examination. Toxicity was graded utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Data analysis was performed using SPSS statistical software version 25.0. Survival analysis for loco-regional control (LRC), Overall Survival (OS), Progression Free Survival (PFS), and Distant Metastasis Free Survival (DMFS) was performed using the Kaplan-Meier method. Median age was 64 years (range, 52 – 97 years). All pts had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2. The most common histology was squamous cell carcinoma (93%). None of the pts had HPV-related disease. Six pts (40%) received prior RT (≥ 60 Gy) at the palliative site. All pts completed at least three “QUAD-SHOT” cycles and all received at least three infusions of concurrent and adjuvant PD-1 inhibitor, pembrolizumab (60%) or nivolumab (40%). The most common presenting symptom was pain (73%). Thirteen (87%) pts had palliation of their presenting symptom. Objective (complete or partial) response to therapy was 60%. Median OS was 7.1 months (range, 1.9 – 24.3 months), and median PFS was 6.5 months (range, 1.9 – 24.3 months). The 6-month LRC, OS, PFS, and DMFS were 100%, 86%, 80%, and 80%, respectively. The 12-month LRC, OS, PFS, and DMFS were 50%, 60%, 30%, and 46% respectively. Radiation Grade 3 toxicity in 3 pts (20%) consisted of mucositis (13%) and dermatitis (7%). The most common toxicity associated with PD-1 inhibitors was Grade ≥ 2 fatigue (53%). Abscopal effect was documented in 2 (13%) pts. Our analysis suggests that QUAD-SHOT palliative radiation with concurrent PD-1 inhibitor for incurable loco-regionally recurrent and/or metastatic squamous cell carcinoma of the head and neck is efficacious and well-tolerated in this group of pts with limited life expectancy. Further studies with larger number of pts are required to better define the optimal sequencing, number of cycles, and type of PD-1 inhibitor in this population.