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
Mell LK, Torres-Saavedra PA, Wong SJ, Chang S, Kish JA, Minn A, Jordan RC, Liu T, Truong MT, Bauman JE, Powell SF, Khomani A, Riaz MK, Raben D, and Le QT. 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. J Clin Oncol 2019; 37.
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.