Durvalumab monotherapy did not meet the primary end point of improving overall survival (OS) vs standard-of-care (SOC) chemotherapy/cetuximab in the PD-L1-high recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) first-line setting, according to updated findings from the phase 3 KESTREL trial. OS benefit in “all-comer” patients who received durvalumab/tremelimumab compared with those who were administered SOC chemotherapy was a secondary end point of the study; however, the KESTREL trial did not meet this end point, either.1
In the international, open-label KESTREL study (NCT02551159), investigators recruited 823 patients with previously untreated recurrent or metastatic HNSCC. Patients were randomly assigned to 1 of 3 treatment arms: durvalumab monotherapy; durvalumab/tremelimumab; or cetuximab plus 5-fluorouracil, cisplatin, and carboplatin (EXTREME regimen).2
The primary end point was the OS advantage with single-agent durvalumab vs the EXTREME regimen in patients with high PD-L1 expression. Secondary end points included OS benefit with durvalumab/tremelimumab vs the EXTREME modality in patients with any or no level of PD-L1 expression (all-comers), high tumor mutational burden, high PD-L1 expression, or a low risk for early mortality. Other secondary outcomes measures included the objective response rate, progression-free survival, and duration of response.2
Though the safety and tolerability of durvalumab—whether administered as a monotherapy or in combination with tremelimumab—were consistent with what was seen in other trials, neither durvalumab approach improved OS, reported AstraZeneca.
Additional data will be released in the future.
- AstraZeneca. Update on KESTREL Phase III trial of Imfinzi with or without tremelimumab in the 1st-line treatment of recurrent or metastatic head and neck cancer. [press release]. AstraZeneca; February 5, 2021.
- ClinicalTrials.gov. Phase III Open Label Study of MEDI 4736 with/without tremelimumab versus standard of care (SOC) in recurrent/metastatic head and neck cancer (KESTREL). NCT02551159. Updated December 10, 2020. Accessed February 19, 2020. https://clinicaltrials.gov/ct2/show/NCT02551159