Xevinapant Plus Chemoradiation Halves Risk of Mortality in Patients With Locally Advanced Head and Neck Cancer
[Presentation title: 3-Years Follow-Up of Double-Blind Randomized Phase II Comparing Concurrent High-Dose Cisplatin Chemo-Radiation Plus Xevinapant or Placebo in High-Risk Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. LBA39]
Adding xevinapant to standard cisplatin-based chemoradiation halved the risk of mortality, compared with chemoradiation alone, in high-risk patients with locally advanced squamous cell carcinoma of the head and neck, according to a study presented at the Virtual 2020 European Society of Medical Oncology (ESMO) Congress.
With 33 months of follow-up, the risk of mortality was reduced by 51% among patients randomised to xevinapant plus chemoradiotherapy compared with chemoradiotherapy alone (hazard ratio [HR] = 0.49; 95% confidence interval [CI], 0.26-0.92; P< .0261).
The 3-year overall survival (OS) rates were 66% and 51%, respectively. Median OS rates were not reached (NR) versus 36.1 months, respectively.
“This is probably the first time in 30 years that such an overall survival benefit has been seen when compared with cisplatin and radiotherapy in this type of cancer,” said Jean Bourhis, MD, University of Lausanne, Lausanne, Switzerland.
The study randomised patients with locally advanced head and neck cancer to receive cisplatin chemotherapy plus radiation, with (n = 48) or without (n = 47). The primary endpoint was locoregional control (LRC).
Data from the 2-year analysis showed LRC rates of 78% with xevinapant compared with 56% for the control group. Median LRC was not reached (NR) in either arm (HR = 0.47; 95% CI, 0.19-1.15; P = .095).
Progression-free survival (PFS) was also significantly improved with xevinapant, which reduced the risk of disease progression or death over chemoradiotherapy alone by 66% (HR = 0.34; 95% CI, 0.17-0.68; P = .0023). The probability of achieving 36-month PFS was 72% compared with 36%, respectively.
“Xevinapant may optimise the efficacy of chemoradiation,” said Dr. Bourhis. “Improved survival and locoregional response rates suggest that xevinapant has the potential to fill an unmet need for this patient population that, despite being one of the most common malignancies worldwide, experiences relapsed disease in approximately 50% of cases. Importantly, the addition of xevinapant resulted in a good safety profile, which did not compromise the standard of chemoradiation delivery.”
The most common adverse events (AEs) with xevinapant included dry mouth and dysphagia.
“Overall, the treatment-emergent AEs didn’t change from the 2-year analysis and regarding the late toxicity, we have a slight increase in grade 1 and 2 late toxicities reported in the xevinapant arm, but no difference in grade 3 or 4,” said Dr. Bourhis. “We can say that the safety with xevinapant was predictable and manageable without increases in severe toxicities.”