Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Abstract

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma

“…Consistent with previous reports 41 , 42 , TP53 was found to be the most frequently mutated gene in our study. In agreement with findings from other neoadjuvant immunotherapy trials for OSCC or HNSCC 13 , 29 , 42 , neither the mutated gene enrichment nor the degree and features of baseline TIL infiltration predicted MPR in our study.…”

“…Consistent with previous reports 41 , 42 , TP53 was found to be the most frequently mutated gene in our study. In agreement with findings from other neoadjuvant immunotherapy trials for OSCC or HNSCC 13 , 29 , 42 , neither the mutated gene enrichment nor the degree and features of baseline TIL infiltration predicted MPR in our study. The limited sample size and the heterogeneity between biopsy and surgically resected tissues might be the reason, although we matched the biopsy and surgically resected tissues by the clinical tumour sites and features, as well as the microscopic tumour cell proportion.…”

Head and Neck Squamous Cell Carcinoma in Elderly Patients: Role of Radiotherapy and Chemotherapy

“…Finally, the role of immune checkpoint inhibitors (ICIs) in the clinical management of LA-HNSCC is currently under investigation in several clinical trials in concurrent, neoadjuvant, and adjuvant settings [83][84][85][86]. ICIs are active agents in recurrent and metastatic HNSCC, and their role with RT in the curative setting is yet to be defined [83,[87][88][89]. Their profile of safety is very attractive, especially for elderly patients [90][91][92].…”

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

“…An ongoing study (NCT03521830) is currently evaluating ipilimumab in association with nivolumab in one of the arms for la-BCC or m-BCC. Although conflicting results have been reported in other neoplasms [ 32 ], dual PD-1 and CTLA-4 blockade with ipilimumab and nivolumab has gained some interest in head and neck SCC [ 33 ] and is currently being studied in cSCC (NCT04620200).…”