Redemption challenge.

Headline: The PD-L1 inhibitor durvalumab is not an appropriate substitute for patients warranting definitive chemoradiation to the head and neck not eligible to receive cisplatin.

The Study: Cetuximab has had a rough couple of years in the treatment of head and neck cancer. Multiple trials including RTOG 1016 and DE-ESCALATE showed that cetuximab is inferior to cisplatin when combined with radiation for p16-positive HNSCC. But what drug should be used in the not uncommon scenario when patients are not candidates for cisplatin? In HN004, 186 patients receiving head and neck radiation with indication for concurrent chemotherapy but who were ineligible for cisplatin were randomized to receive concurrent cetuximab or durvalumab. Why durva? Because PD-L1 inhibition has proven effective for metastatic disease. Unfortunately, the trial was closed to further accrual after finding at the first interval analysis that locoregional failure at 2 years was more than doubled with durvalumab (32% v 15%). A post-hoc subset analysis revealed poor outcomes with durva were driven by p16- disease, where p16+ disease did well regardless. What about carboplatin, you ask? Retrospective data from the VA System indicated a survival advantage with carboplatin as compared to cetuximab.

TBL: Cetuximab remains the cisplatin-sub with the most robust prospective data for cisplatin ineligible patients with indications for definitive chemoradiation to the head and neck. | Mell, ASTRO 2022