Abstract 869P
Background
Immune checkpoint inhibitors (ICI) have an established role in the management of recurrent/metastatic SCCHN and are being investigated in the curative setting. We evaluated the novel approach of combining Nivo, a PD-1 inhibitor, and Ipi, a CTLA-4 inhibitor, with RT in pts with high-risk LA SCCHN.
Methods
Newly diagnosed, chemotherapy eligible pts with AJCC 7th edition stage IVA-IVB SCCHN of the oropharynx (OP), hypopharynx, and larynx (HPV+ OP were T4, N2c or N3) received Nivo (3 mg/kg Q2 weeks x 17) and Ipi (1 mg/kg Q6 weeks x 6) starting 2 weeks prior to RT and 70 Gy in 2 Gy/fraction/day using VMAT. The primary objective was safety of concurrent ICI-RT. Secondary objectives included PFS and correlative studies.
Results
24 pts were enrolled; median age 60 (48-77); 20 male; 16 OP (14 HPV+), 2 hypopharynx, and 6 larynx; AJCC 7th ed. stage IVA (23), IVB (1). Tumor PD-L1 in 22/24 pts: 5 with combined positive score (CPS) <1, 8 CPS 1-19 and 9 CPS ≥20. Grade 3 acute in-field adverse events (AEs) occurred in 17/24 pts (71%) during concurrent ICI-RT (9 mucositis, 6 dysphagia, 5 dermatitis, 4 odynophagia, 1 dysphonia). During ICI maintenance, 5 pts developed in-field ulcerations at the primary site at a median of 3 months (mo) post RT; 1 pt died of carotid bleeding with no evidence of active cancer; 4 pts developed in-field necrosis. 7 pts discontinued ICI at >3 mo post-RT: 1 due to immune AE, 5 due to in-field ulcerations, 1 due to persistent mucositis. 4 pts (17%) had grade 3+ immune AEs: 1 lipase elevation, 1 colitis, 2 rash. At 1 year 3 pts were gastrostomy tube dependent. With median follow-up of 29 mo (14-44) 20/24 pts (83.3%) are alive with no evidence of disease. 3 pts (2 HPV+) recurred distantly: 2 with lung (at 12 mo and 25 mo); 1 in mediastinal lymph nodes (at 12 mo). Locoregional control remains 100%.
Conclusions
Dual ICI and RT combination was feasible and notably achieved no locoregional relapses in high-risk LA SCCHN. We observed in-field ulceration/necrosis that may be attributed to the potent radiosensitizing effect of dual blockade. This regimen is worthy of further investigation.
Clinical trial identification
NCT03162731.
Editorial acknowledgement
Legal entity responsible for the study
Thomas Jefferson University.
Funding
Bristol Myers Sqibb.
Disclosure
J.M. Johnson: Financial Interests, Personal, Other, Consulting for Molecular Tumor Boards: Foundation Medicine. J.M. Curry: Financial Interests, Personal, Advisory Board: Rakuten Medical. All other authors have declared no conflicts of interest.