1117PD - Pembrolizumab and radiotherapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) with contraindication to cisplatin therapy

Abstract

BackgroundConcurrent bolus cisplatin with radiation therapy (XRT) is a standard of care for the treatment of LA-HNSCC. Contraindications such as hearing loss, tinnitus, renal dysfunction or neuropathy are common. Radiation elicits and promotes tumor-directed immune-stimulation, which may potentiate anti-PD-1 therapy. MethodsThis single arm, multi-institution, phase II study (NCT02609503) enrolled 29 patients (pts) with LA-HNSCC who are platinum ineligible. Patients received XRT concurrently with 3 cycles of pembrolizumab 200mg q3 weeks followed by 3 adjuvant cycles. The primary endpoint was progression free survival (PFS). Acute toxicity included events occurring within 6 months of completing XRT. ResultsThe primary reasons for cisplatin ineligibility included abnormal hearing (48.3%), tinnitus (20.7%), nephropathy (17.2%), neuropathy (6.9%) and diabetes with poor control (6.9%). Oropharynx was the most common site of primary disease (20/29, 69.0%), of which 17/20 (85%) were p16 positive. All 29 pts completed 70Gy XRT while 25 pts (86.2%) received 6 cycles of pembrolizumab. Radiation dermatitis, xerostomia, and mucositis were the most common acute toxicities (Table). Grade 3/4 toxicities were rare except for lymphopenia (17/29, 58.6%). Feeding tube placement (4/29, 13.8%) and treatment associated hospitalizations (3/29, 10.3%) were also uncommon. Currently, 24/29 (82.8%) pts are alive and free of disease progression, with median follow up of 15 months (range 8-29 months).Table: 1117PDTable: 1117PDToxicity code (n, %)Grade 1Grade 2Grade 3Grade 4Dermatitis radiation8 (27.6)16 (55.2)..Xerostomia13 (44.8)11 (37.9)..Mucositis oral2 (6.9)15 (51.7)7 (24.1).Dysgeusia17 (58.6)6 (20.7)..Lymphopenia2 (6.9)4 (13.8)15 (51.7)2 (6.9)Fatigue15 (51.7)3 (10.3)..Nausea10 (34.4)1 (3.5))2 (6.9).Dysphagia2 (6.9)8 (27.6)2 (6.9).Anemia10 (35.5)1 (3.5)..Weight loss6 (20.7)5 (17.2)..Neutropenia7 (24.1)3 (10.3).. ConclusionsThis is the first study to report acute toxicities of combining pembrolizumab with radiation in LA-HNSCC. Pembrolizumab does not potentiate typical XRT associated toxicities and no unexpected immune related adverse events were observed. Further, lower rates of feeding tube placement and grade 3/4 dermatitis, xerostomia, and mucositis were noted when compared to RTOG1016 (concurrent XRT with cisplatin or cetuximab in LA-HNSCC). Clinical trial identificationNCT02609503. Legal entity responsible for the studyThe authors. FundingMerck Sharp & Dohme Corp. DisclosureAll authors have declared no conflicts of interest.