2557 - Pembrolizumab and radiotherapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) with contraindication to cisplatin therapy

Background

Concurrent 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.

Methods

This 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.

Results

The 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 70 Gy 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: 1117PD

Conclusions

This 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 identification

NCT02609503.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Merck Sharp & Dohme Corp.

Disclosure

All authors have declared no conflicts of interest.