Treatment Considerations for Patients with Locoregionally Advanced Head and Neck Cancer with a Contraindication to Cisplatin

Abstract

Significant advancements have been made in the treatment of locally advanced head and neck cancer, predominantly driven by the integration of concurrent chemotherapy with radiation therapy as a standard of care for many patients. The most heavily investigated chemotherapeutic is cisplatin, yet many patients are ineligible for cisplatin due to the presence of pre-existing medical comorbidities. Moreover, given the toxicity profile of cisplatin, identifying which patients stand to benefit from cisplatin is challenging, which is particularly evident in older patients. Efforts to better risk-stratify patients based on age, performance status, and the degree of pre-existing comorbidities are ongoing and have been increasingly utilized in national clinical trials. In parallel, exploration into alternative systemic agents, including novel targeted therapies and immunotherapies, in cisplatin-ineligible patients are rapidly expanding. Cumulatively, identifying appropriate treatment paradigms in patients who harbor contraindications to cisplatin can not only improve clinical outcomes but also critically mitigate detrimental adverse effects.

Keywords: Chemotherapy; Cisplatin-ineligible; Head and neck cancer; Radiation therapy.

Fig. 1

Schema of upcoming NRG-HN012 trial to compare RT with concurrent and adjuvant xevinapant, a second mitochondria-derived activator of caspases (SMAC) mimetic, vs. RT with concurrent cetuximab in patients with locally advanced head and neck cancer who have a contraindication to cisplatin.