855MO - Adjuvant immunotherapy after salvage surgery in head and neck cancer squamous cell carcinoma (HNSCC): Phase II trial evaluating the efficacy and the toxicity of Nivolumab (ADJORL1)

Background

Treatment of locoregional failures or second primary in HNSCC in previously irradiated areas is a challenge. Reirradiation is currently the only treatment which can improve disease-free survival (DFS) after salvage surgery (SS) even if it has no impact on the overall survival (OS) because of high toxicity, showing the need to investigate other adjuvant therapies (AT) such as immunotherapy. The objectives of this study were to evaluate the 2-year DFS and OS of patients (pts) treated with nivolumab (N) after SS, the toxicity of N in this population and to determine biomarkers of response.

Methods

This multicentric non-randomized phase II add trial pts with recurrence or second primary of HNSCC in previously irradiated area, operated by SS with curative intent, more than 6 months after initial radiotherapy and of bad prognosis justifying an AT. Within 8 weeks of SS, 240 mg of adjuvant N was administrated every 2 weeks during the first 3 months, and then N 480 mg every 4 weeks was administrated for the next 3 months. The design was performed using a binomial test with a 2-year DFS < 40% as ineffective (α=10%, power=80%).

Results

Between February 2018 and March 2021, 57 patients were included and treated. Median age was 61 years, 80% male. Median number of cycles of N was 9 (from 3 to 10). The reasons for off treatment were: 60% treatment completion, 21% tumor progression, 12% toxicity, 7% Others. 2-year DFS was 46.6%, 90%CI[36.1-57.5%] for the main endpoint and 2-year OS was 67.3%, 95%CI[54.2-78.2%]. Median follow-up was 48.2 months (from 5.3 to 59.6). 17 adverse events (AEs) grade ≥3 were related to N (mainly pancreatic hepatobiliary disorders, colitis, myositis andmyocarditis) and occurred in 11 pts (19%). No drug-related death occurred. Biomarkers data (CPS, Immunoscore) will be presented.

Conclusions

N as AT after SS is well tolerated. The 2-year DFS and OS compared favorably with those from historical data of reirradiation trials. In JANORL2 trial (Radiother Oncol 2018), 2-year DFS and OS were respectively 33.4%, 95%CI [22.1-47.0%] and 54.0%, 95%CI [40.6-66.8%]. These encouraging results warrant further investigations.

Clinical trial identification

NCT03406247.

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy Promotion.

Funding

BMS.

Disclosure

A. Daste: Financial Interests, Personal, Advisory Board: Merck, BMS, MSD. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Innate Pharma, Merck Serono, Roche, Seagens, Iteos, Elevar, Hookipa; Non-Financial Interests, Principal Investigator: AstraZeneca. F. Rolland: Financial Interests, Personal, Advisory Board: Pfizer, Eisai, MSD, Merck Serono; Financial Interests, Institutional, Coordinating PI: Exelixis; Financial Interests, Institutional, Local PI: BMS, Ipsen. A.C. Johnson: Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Local PI, Skyscraper 09 trial: Roche; Financial Interests, Institutional, Local PI, Buran trial: Adlai Nortye; Other, Conference & travel expenses: Lilly, Gilead, AstraZeneca. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA pharmaceutics, MSD, Debiopharma, Ayala, Gilead; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, Sanofi. All other authors have declared no conflicts of interest.