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

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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.

References

  1. 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.
  2. 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

Topics:

Head and Neck Cancer