Safety of radiotherapy with concurrent and adjuvant MEDI4736 (durvalumab) in patients with locoregionally advanced head and neck cancer with a contraindication to cisplatin: NRG-HN004

Document Type

Conference Proceeding

Publication Date


Publication Title

J Clin Oncol


Background: MEDI4736 (durvalumab), a PD-L1 inhibitor, has shown promising antitumor activity and safety in head and neck squamous cell carcinoma (HNSCC). A phase II/III trial with lead-in component was designed to evaluate the safety and efficacy of concurrent and adjuvant MEDI4736 with radiation therapy (RT) for HNSCC patients with a contraindication to cisplatin. Safety data for 10 patients on the lead-in study are reported. Methods: Eligible patients had previously untreated locoregionally advanced unresected SCC of the larynx, hypopharynx, oropharynx (OPX), oral cavity, or unknown head/neck primary (AJCC 7th stage III-IVB). Contraindications to cisplatin included renal or hearing impairment, age > 70 with moderate or severe comorbidity/vulnerability to cisplatin, or age< 70 with severe comorbidity/vulnerability, based on 6 validated indexes. Intravenous MEDI4736 1500 mg was delivered at weeks -2, 2, 6, 10, 14, 18, and 22 with RT (70 Gy in 35 daily fractions weeks 1-7). The primary endpoint was dose-limiting toxicity (DLT), defined as a high-grade adverse event (AE; NCI CTCAE version 4.0) definitely/probably related to MEDI4736 up to 4 weeks following completion of RT; 0-2 DLTs in 8 evaluable patients was considered acceptable. Results: Characteristics of the 10 enrolled patients were: 30% age > 70, 90% male, 100% Caucasian, 40% ECOG performance status 0, 60% modified Charlson Comorbidity Index > 1, 60% >10 pack-years, 20% larynx, 60% p16+ OPX, 50% T3-4 and 80% N2-3 disease. All 10 patients had > 2 contraindications to cisplatin. All 10 patients completed RT and were evaluable. 8 of 10 patients received all 7 doses of MEDI4736 and 1 patient is still on MEDI4736 after 6 doses. 1 patient received 2 doses then discontinued due to AE (diarrhea possibly related to MEDI4736). No DLTs were observed. No grade 4-5 AEs were observed. Grade > 3 AEs possibly related to MEDI4736 were: diarrhea (n=1), nausea (1), and vomiting (1). No grade > 3 AEs were rated as definitely or probably related to MEDI4736. Conclusions: MEDI4736 is safe and feasible to administer concurrently with RT for patients with HNSCC with a contraindication to cisplatin.





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