In a phase Ib study reported in the Journal of Clinical Oncology, Powell et al found that the addition of pembrolizumab to curative chemoradiotherapy was safe and associated with response in patients with locally advanced head and neck squamous cell carcinoma.
Study Details
The U.S. multicenter study enrolled 59 patients with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB head and neck squamous cell carcinoma between November 2015 and October 2018. Of these patients, 34 had human papillomavirus (HPV)-positive disease. Patients could not have received prior radiotherapy or systemic therapy.
Treatment consisted of pembrolizumab at 200 mg given 7 days before chemoradiotherapy (day −7); two additional doses on days 15 and 36 during chemoradiotherapy (concurrent); and after completion (consolidation) every 3 weeks on days 57, 78, 99, 120, and 141. Chemoradiotherapy was started on day 1 with cisplatin at 40 mg/m2 weekly for a total of six planned doses with concomitant intensity-modulated radiotherapy at 70 Gy as 2 Gy daily over 35 fractions.
Toxicity
Discontinuation of pembrolizumab due to immune-related adverse events was required in five patients (9%), with all discontinuations occurring during concurrent chemoradiotherapy. Overall, 98% of patients completed the full planned 70-Gy dose of radiotherapy with no delays ≥ 5 days, and 88% received the target cisplatin dose of ≥ 200 mg/m2.
KEY POINTS
- The addition of pembrolizumab to chemoradiotherapy was safe and did not impair ability to deliver expected doses of chemoradiotherapy.
- Complete response rates at end of treatment were 85% and 78% in HPV-positive and HPV-negative disease, respectively.
The most common treatment-related immune-related adverse events of any grade were pruritus (14%) and hyponatremia, as well as decreased lymphocyte count, hypothyroidism, and skin and subcutaneous tissue disorders (5% each). The most common grade 3 or 4 adverse events were decreased lymphocyte count (88%), decreased white blood cell count (54%), dysphagia (49%), and weight loss (32%).
Responses
Among 57 patients evaluable for response, complete response at end of treatment was observed in 29 (85%) of 34 patients with HPV-positive disease and in 18 (78%) of 23 with HPV-negative disease. Median follow-up was 28.4 months among HPV-positive patients and 17.5 months among HPV-negative patients. Among HPV-positive patients, estimated 1- and -2-year overall survival was 97% and 97%, and 1- and 2-year progression-free survival was 97% and 93%. Among HPV-negative patients, with shorter follow-up, estimated 1-year overall survival was 87% and 1-year progression-free survival was 73%.
The investigators concluded, “Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in head and neck squamous cell carcinoma. Early efficacy data support further investigation of this approach.”
Steven F. Powell, MD, of Sanford Cancer Center, Sanford Health, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Merck Investigator Studies Program and the National Institute of General Medical Science. For full disclosures of the study authors, visit ascopubs.org.
