In the randomized phase III Study CA209141, Nivolumab (N) demonstrated significant overall survival benefit as treatment for platinum refractory R/M SCCHN and is now approved for these patients. N has demonstrated a manageable safety profile compared to chemotherapies commonly used in patients with platinum-refractory R/M SCCHN. The main objective of the study is to provide additional insight into the frequency of high-grade AEs related to N and their outcome.
Between August 2017 and October 2017, 75 patients were included in the multicenter, open-label, non-controlled phase II safety study TOPNIVO. The main inclusion criteria were patients with platinum refractory R/M SCCHN with progressive disease, ECOG 0-2. Patients received N 3mg/kg every 2 weeks intravenously over 30 minutes. We report here the safety results of the three first months of treatment.
Of 73 patients treated with N, median age was 64.0 yr, 75% were male, 23% were ECOG 0, 62% 1, 15% 2, 81% were current or former smoker. The primary site of cancer was oral cavity 27%, oropharynx 34%, larynx 19%, hypopharynx 19%. 36% had loco regional relapse, 34% had metastatic disease and 30% had both. 48% had received one prior line of chemotherapy and 32% two prior lines. 37 pts (51%) received at least 6 administrations of N during the first three months of treatment. 5% of administrations were delayed, mainly for intercurrent disease. 38 pts (52%) ended N within the first three months, 28 pts for progressive disease, 8 due to death (thrombus 1pt, progressive disease or related to cancer 7 pts), 1 for pneumonitis, 1 for pain. 35 pts experienced at least 1 AE grade 3/4/5. On the 52 AEs grade 3-4, 7 (mainly asthenia and lipase increase) were related to N. On the 7 AEs grade 5, 1 (pneumonitis) was related to N. 28 pts (38%) experienced at least 1 SAE. On the 38 SAEs, 3 were related to N. 6 patients experienced tumor bleeding (grade 1 2 pts, grade 2 1 pt, grade 3 1 pt, grade 4 1 pt, grade 5 1 pt), none were related to N.
The first results of the TOPNIVO study show an acceptable toxicity profile without additional toxicities compared to what has been described previously.
Clinical trial identification
NCT03226756; EudraCT: 2017-000424-10.
Legal entity responsible for the study
C. Even: MSD, Merck Serono, BMS, AstraZeneca, Innate Pharma. E. Saada-Bouzid: Advisory board and consulting: BMS, Merck Serono, AstraZeneca. C. Borel: Advisory board immunotherapy: AstraZeneca, BMS; Symposia honoraria: Merck Serono, BMS; Congress: Merck Serono. D. Cupissol: Boards: Merck, AstraZeneca, BMS. F. Huguet: Merck Serono, BMS, AstraZeneca, MSD. J. Guigay: Consulting or advisory role: Merck Serono, BMS, Innate Pharma, AstraZeneca; Research funding: BMS, GSK, Merck Serono. All other authors have declared no conflicts of interest.