Barbara Burtness, MD
Discussing this study in her Highlights of the Day at the 2023 ASCO Annual Meeting was Barbara Burtness, MD, the Anthony N. Brady Professor of Medicine and Chief Translational Research Officer at Yale Cancer Center, New Haven, Connecticut. She noted that the premise of the FRAIL-IMMUNE trial starts with recognition that PD-1 inhibition has entered the standard of care in the first-line management of recurrent or metastatic head and neck squamous cell carcinoma for patients with PD-L1–expressing tumors.
In KEYNOTE-048, pembrolizumab monotherapy led to a median overall survival of 12.3 months, and when combined with cisplatin or carboplatin and fluorouracil, the median overall survival was 13.6 months.1 The benefit was actually higher for the 36% of patients older than age 65, with a hazard ratio of 0.54, as compared with 0.74 for younger patients. And at the European Society for Medical Oncology (ESMO) Congress 2022, KEYNOTE-B102 showed that a regimen of pembrolizumab, paclitaxel, and every-3-week carboplatin is active, with a response rate of 42.7% in a phase II trial in which 46% of patients were aged 65 or older, she said.
Dr. Burtness continued: “We also know that although PD-L1 inhibition is active in head and neck cancer, these drugs have not become a standard of care. Durvalumab monotherapy was not superior to the EXTREME regimen (platinum, fluorouracil, and cetuximab) in the KESTREL study.3”
These considerations led to the design of the FRAIL-IMMUNE trial of durvalumab plus weekly carboplatin AUC 2 and paclitaxel at 80 mg/m2 in patients deemed ineligible for cisplatin; all had a performance status of 0 or 1. The 12-month overall survival rate, the primary endpoint, was 63%, the median survival was 18 months, and the objective response rate was 71%, “not something we talk about often in this disease, so very impressive,” Dr. Burtness commented.
“This trial adds to the evidence that carboplatin and paclitaxel combined with immune checkpoint inhibition is safe and effective, and the regimen was tolerable for patients aged 70 or older or who have some comorbidity. However, given the negative first-line phase III trial,2 I don’t think it establishes a role for durvalumab in this disease,” she said.
DISCLOSURE: Dr. Burtness has served as a consultant or advisor to AbbVie, ALX Oncology, Arvinas, Coherus Biosciences, CUE Biopharma, Genentech/Roche, IO Biotech, Kura Oncology, MacroGenics, Merck, Merck KGaA, and Vaccinex.
REFERENCES
1. Burtness B, Harrington KJ, Greil R, et al: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. Lancet 394:1915-1928, 2019.
2. Dzienis MR, Cundom JE, Fuentes CS, et al: Pembrolizumab + carboplatin + paclitaxel as first-line therapy in recurrent/metastatic head and neck squamous cell carcinoma: Phase VI KEYNOTE-B10 study. ESMO Congress 2022. Abstract 651O. Presented September 12, 2022.
3. Psyrri A, Fayette J, Harrington K, et al: Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study. Ann Oncol 34:262-274, 2023.
