Prof. Jean Bourhis, Department Head of Radio-Oncology at the University Hospital of Lausanne and Lead Investigator of Centre Hospitalier Universitaire Vaudois explains the ESMO 2020 Abstract Pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC): Results of the GORTEC 2015-01 “PembroRad” randomized trial.
This new combination was tested in a randomized trial against the well-established standard of care (SOC) cetuximab-RT in LA-HNSCC on the basis of the hypothesis of the possible synergistic effect of anti-PD1 pembrolizumab when combined with RT.
In this phase II randomized trial, patients with the oral cavity, oropharynx, hypopharynx, and larynx SCC untreated at stage III-IVa-b and unfit for high-dose cisplatin were enrolled. Up to 69,96 Gy concomitant with cetuximab (Cetux-RT arm: 400 mg / m2 loading dose and 250 mg / m2 weekly) or pembrolizumab (Pembro-RT arm: 200 mg Q3W during RT) received IMRT once daily in patients. The primary endpoint was the 15-month Loco-Regional Control (LRC) pace, and Progression-free Survival (PFS), Overall Survival (OS), and tolerance were the secondary endpoints. In order to detect a 60 to 80 percent difference between arms in the 15-month LRC, 66 patients per arm were expected to be included to achieve a power of at least 0.85 at a 2-sided significance level of 0.20.
131 patients were randomized and monitored by 27 centers between May 2016 and October 2017: 65 patients in the Cetux-RT arm and 66 in the Pembro-RT arm. The median age was 65 years, 92% were smoking, 60% were oropharyngeal (46% p16 +), 41% were N2c-N3 with 25%, 56% and 19% were stage III, IVa, and IVb respectively. The median follow-up time for both arms was 25 months. In the Pembro-RT arm, acute toxicity was lower than in the Cetux-RT arm: 74% vs 92% in patients with at least 1 ⁇ 3 acute adverse effects (p=0.006), primarily due to radiation-field dermatitis, mucositis, and cutaneous rash. In the Cetux-RT arm and 60 percent in the Pembro-RT arm, LRC at 15 months was 59 percent, not substantially different: OR=1.05 (95 percent CI: 0.43-2.59, p=0.91). In the Cetux-RT arm, the 2-year PFS average was 40 percent vs. 42 percent in the Pembro-RT arm. No substantial difference was found between the PFS arms: HR=0.83 (95 % CI 0.53-1.29, p=0.41). In the Cetux-RT arm, the 2-year OS average was 55%, compared with 62% in the Pembro-RT arm. OS did not vary substantially between the arms: HR=0.83 (95 % CI: 0.49-1.40, p=0.49).
The anti-PD1 pembrolizumab concomitant with RT did not boost carcinological outcomes relative to SOC cetuximab-RT but appeared less toxic.
NCT 02707588 for clinical trial recognition.