Study Finds Durvalumab Plus Carboplatin and Paclitaxel Effective, Tolerable in Frail Patients With Head and Neck Cancer

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As a first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma, the PD-L1 inhibitor durvalumab plus weekly carboplatin and paclitaxel provided clinically significant efficacy in the phase II FRAIL-IMMUNE (GORTEC 2018-03) trial.1 This regimen may prove to be an effective first-line option, especially for patients who cannot tolerate cisplatin, said Jérome Fayette, MD, PhD, of Centre Léon Bérard, Lyon, France, who reported the findings at the 2023 ASCO Annual Meeting.1

“This regimen [durvalumab plus weekly carboplatin and paclitaxel] may prove to be an effective first-line option [in advanced head and neck cancer], especially for patients who cannot tolerate cisplatin.”
— Jérome Fayette, MD, PhD

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“This experimental combination is safe, with a tolerability profile that is more favorable than that reported in the KEYNOTE-0482 study,” he said. The three-arm KEYNOTE-048 trial evaluated pembrolizumab alone, pembrolizumab plus a platinum and fluorouracil, and cetuximab plus a platinum and fluorouracil.

Dr. Fayette described the rationale for this approach, noting that despite the benefits achieved with pembrolizumab and chemotherapy in the first-line setting, that regimen is associated with substantial toxicity (85% rate of grade 3 or 4 adverse events), thus precluding its use in fragile patients. Cisplatin and carboplatin have comparable efficacy when combined with fluorouracil, and although cisplatin is preferred, it is “safe and efficient” to substitute carboplatin when patients cannot tolerate cisplatin, he noted.

With these points in mind, Dr. Fayette and colleagues designed and tested the efficacy of an alternative first-line treatment of relapsed or metastatic squamous cell carcinoma of the head and neck in cisplatin-ineligible patients: PD-L1 inhibition with durvalumab, plus weekly carboplatin and paclitaxel.

FRAIL-IMMUNE Details and Results

Patients received four cycles of durvalumab at 1,500 mg on day 1 every 4 weeks, plus chemotherapy with carboplatin AUC 2 and paclitaxel at 80 mg/m2 on days 1, 8, and 15; patients continued durvalumab at 1,500 mg every 4 weeks for a maximum of nine cycles (36 weeks). At least 38 “successes” among 64 patients were needed to consider the treatment worthy of further investigation in this indication, he said.

“The efficacy rule for the primary endpoint was met, with 40 observed successes vs 38 required,” Dr. Fayette reported. These 40 patients were alive at 12 months, yielding a 12-month overall survival rate of 63%, a 24-month overall survival rate of 45%, and a median overall survival of 18 months. Median progression-free survival was 7 months, the objective response rate was 71%, and the median duration of response was almost 6 months.

Benefit was associated with PD-L1 expression. The 12-month survival rate was 76% for patients with PD-L1 ≥ 20 vs < 20 (by composite positive score) and 70% vs 46%, respectively, for those with PD-L1 ≥ 1 vs < 1. The regimen was effective in patients regardless of whether they tested positive or negative for human papillomavirus (HPV), with median overall survival not reached in HPV-positive patients and 25 months in HPV-negative patients (P = .07); in both groups, around two-thirds of patients were alive at 12 months.

The most common adverse events related to durvalumab were limited to grade 1 or 2 except for two (3%) patients experiencing diarrhea. Grade ≥ 3 toxicities attributed to chemotherapy included primarily neutropenia (55%) and anemia (22%). “Hematologic tolerance can be improved by a 2-day infusion of growth factors,” suggested Dr. Fayette. 

DISCLOSURE: Dr. Fayette reported financial relationships with AstraZeneca, Bristol Myers Squibb, Hookipa Pharma, Merck Serono, Merck Sharp & Dohme, Roche, Elevar Therapeutics, ITeos Therapeutics, and Seagen.


1. Fayette J, Cropet C, Gautier J, et al: Results of the multicenter phase II FRAIL-IMMUNE trial evaluating the efficacy and safety of durvalumab combined with weekly paclitaxel carboplatin in first line in patients with recurrent/metastatic squamous cell carcinoma of the head and neck not eligible for cisplatin-based therapies. 2023 ASCO Annual Meeting. Abstract 6003. Presented June 5, 2023.

2. 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.

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