A Matched Comparison of Early Toxicity in p16+ Oropharynx Cancer Treated With Definitive Chemoradiation With or Without Nivolumab.

PURPOSE/OBJECTIVE(S) To compare acute toxicity and quality of life (QOL) outcomes up to 3 months post chemoradiotherapy (CRT) versus CRT with nivolumab (iCRT) in locally advanced p16+ oropharyngeal cancer (OPC). MATERIALS/METHODS Matched cohorts with AJCC 8 stage III p16+ OPC patients treated at a single institution on two prospective protocols were compared: 1) CRT (Carboplatin + Paclitaxel) to 70 Gy with concurrent and 3 months of adjuvant nivolumab (iCRT) 2) CRT (Carboplatin or Cisplatin) to 70-80 Gy. 30 CRT patients were matched 2:1 to 15 iCRT patients according to primary site and tumor volume. In both groups, we compared the following clinical variables during and within 3 months of RT: physician graded mucositis, ED visits/hospitalizations, treatment interruptions, opioids requirements, and need for IV hydration or feeding tube (FT). The iCRT patients reported weekly Common Terminology Criteria for Adverse Events (CTCAE) during RT. Videofluoroscopy (VFSS) and validated QOL patient reported outcomes (PROs) were completed at baseline and 3 months. PROs were scored for minimal clinically important difference (MCID) changes. Student t-tests and chi-square were used to compare groups. RESULTS Clinical characteristics were balanced in mean age (P = 0.065), tumor volume (P = .74), base of tongue vs tonsil site (P = .88). Current smoking and pack year history were higher in the CRT patients (P = 0.003). iCRT patients had significantly higher rates of grade 3+ mucositis (87 vs 17%, P < 0.001), persistent opioid use at 3mo post-RT (69 vs 17%, P = 0.002), and missed chemotherapy doses (47 vs 13%, P = 0.04). No patient had any RT interruption. Non-significantly increased endpoints in iCRT patients included ED visits (53 vs 23%, P = 0.09), hospitalizations (40 vs 20%, P = .28), FT use (53 vs 33%, P = .33) and need for IV hydration during therapy (80% vs 47%, P = 0.07). From the 10 iCRT and 30 CRT patients who had complete PROs, iCRT patients reported significant MCID changes at 3 months in global QOL (80% vs 20%, P = 0.002), pain (90 vs 40%, P = 0.02) and sticky saliva (100% vs 57, P = 0.03), while changes in taste (90% vs 60%, P = .17) and swallow function (90% vs 50%, P = 0.06) were non-significantly worse in iCRT patients. In addition, from the 8 iCRT and 27 CRT who had complete VFSS scored by SLP at the time of this interim evaluation, there were increased aspiration events in the iCRT from baseline to 3 months (63 vs 44%, P = 0.06). Finally, weekly PROs during RT in iCRT patients revealed severe taste changes (78%), severe mouth sores (54%), and severe dry mouth (62%) by week 3. CONCLUSION Despite increased smoking history and RT boost, CRT patients exhibited fewer acute toxicities compared to iCRT patients. iCRT patients reported severe taste changes, mucositis, and xerostomia early in treatment. As many trials are currently ongoing to establish the oncologic benefit of concurrent immunotherapy, attention must be paid to acute and late toxicities as well as their impact on QOL in order to define their therapeutic utility.