Jean Bourhis, MD, PhD, Radiation Oncology, Centre Hospitalier Universitaire Vaudois, discusses the overall survival (OS) benefit of xevinapant (Debio 1143) plus chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC).

A phase 2 trial (NCT02022098) evaluated xevinapant plus chemoradiotherapy vs placebo plus chemoradiotherapy in patients with locally advanced HNSCC.

Previously reported data from the trial showed a progression-free survival benefit for xevinapant vs placebo, and updated findings presented at the 2022 ESMO Congress also demonstrated an OS benefit at 5 years with xevinapant vs placebo, Bourhis explains.

Patients treated with xevinapant plus chemoradiotherapy achieved a 5-year OS rate of 53%, compared with 28% for those given placebo plus chemoradiotherapy, Bourhis continues. Over the past decade, investigators have not been able to find a treatment in HNSCC to improve upon the standard of care of cisplatin plus radiotherapy, Bourhis adds. It is now important to confirm the phase 2 results with xevinapant plus chemoradiotherapy in a randomized phase 3 study, Bourhis concludes.

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Jean Bourhis, MD, PhD, discusses the overall survival benefit of xevinapant plus chemoradiotherapy in head and neck squamous cell carcinoma.


Dr. Bourhis on the OS Benefit of Xevinapant Plus Chemoradiotherapy in HNSCC

Jean Bourhis, MD, PhD, Radiation Oncology, Centre Hospitalier Universitaire Vaudois, discusses the rationale to explore Debio 1143 in patients with head and neck cancer.

The current standard of care for patients with locally advanced squamous cell carcinoma of the head and neck is concurrent chemoradiation. However, a subset of these patients have a high risk of relapse, says Bourhis. Once patients relapse, there are limited treatment options available. Given this high unmet clinical need, researchers sought to evaluate the addition of Debio 1143 to concurrent high-dose cisplatin and chemoradiation as a way to overcome resistance to chemoradiation.

In preclinical models, Debio 1143 had shown promising antitumor activity in combination with cisplatin and radiation, says Bourhis. Accordingly, investigators launched a phase I/II trial (NCT02022098), in which the recommended phase II dose of Debio 1143 was compared with placebo in combination with concurrent chemoradiation.

Dr. Bourhis on the Rationale to Explore Debio 1143 in Head and Neck Cancer

Jean Bourhis, MD, PhD, Radiation Oncology, Centre Hospitalier Universitaire Vaudois, discusses the results of a phase II trial evaluating the addition of Debio 1143 to concurrent high-dose cisplatin and chemoradiation in high-risk patients with locally advanced squamous cell carcinoma of the head and neck.

Data presented at the 2019 ESMO Congress demonstrated that the addition of Debio 1143, a first-in-class oral inhibitor of apoptosis proteins, to standard chemoradiation had a comparable safety profile to standard chemoradiation and placebo in patients with locally advanced head and neck cancer. Adverse events were mostly comparable between arms; however, a higher incidence of grade 3 mucositis, dysphagia, and anemia were reported in the Debio 1143 arm.

At 18 months, investigators reported a 21% improvement in the rate of locoregional control with the addition of Debio 1143 (odds ratio = 2.69; 95% CI, 1.13-6.42; 

 = .026). Moreover, the median progression-free survival was not yet reached at the time of data cutoff versus 16.9 months in the placebo arm (HR, 0.37; 95% CI, 0.18-0.76; 

Jean Bourhis, MD, PhD

Articles

Dr. Bourhis on the OS Benefit of Xevinapant Plus Chemoradiotherapy in HNSCC

Dr. Bourhis on the Rationale to Explore Debio 1143 in Head and Neck Cancer

Dr. Bourhis on Results of the Phase II Trial With Debio 1143 in Head and Neck Cancer