5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC

Pembrolizumab combined with 5-FU-free paclitaxel and carboplatin was effective and tolerable as a first-line treatment for patients with recurrent or metastatic head and neck squamous cell cancer (R/M HNSCC) and may be an alternative for standard 5-FU containing regiment, preliminary results from the phase 4 KEYNOTE-B10 trial demonstrated.

Standard-of-care treatment for patients with R/M HNSCC is pembrolizumab combined with 5-FU and platinum chemotherapy [1]. However, alternatives to 5-FU are needed based on their toxicities, patient inconvenience and complications [2]. The phase 4 KEYNOTE-B10 trial (NCT04489888) evaluated the efficacy and safety of pembrolizumab in combination with 5-FU-free carboplatin plus paclitaxel as first-line treatment for R/M HNSCC patients. Dr Marcin Dzienis (Gold Coast University Hospital, Australia) presented the first results of this ongoing study [3].

The KEYNOTE-B10 trial enrolled all patients with previously untreated R/M HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx. Participants were treated with pembrolizumab (200 mg every 3 weeks) for ≤35 cycles, paclitaxel (100 mg/m² every week on days 1 and 8; or 175 mg/m² every 3 weeks on day 1) for 6 cycles, plus carboplatin (AUC 5 mg/mL/min every 3 weeks) for 6 cycles. The primary endpoint is the objective response rate (ORR). Results from the first 92 participants were presented.

After a median follow-up of 8.2 months, 51 participants had discontinued treatment: 31 due to disease progression, and 10 due to adverse events. ORR was 42.7% (4.9% complete responders). ORR was irrespective of age, sex, HPV status, and PD-L1 expression. The median time-to-response was 1.5 months and the median duration of response was 5.5 months.

Grade ≥3 treatment-related adverse events (AE) were observed in 70.7% of patients and serious treatment-related AEs in 17.4% of patients. The most common grade ≥3 treatment-related AEs were neutropenia, anaemia, and leukopenia.

Based on these (preliminary) results, Dr Dzienis concluded: “Efficacy and safety results of this trial suggest that this 5-FU-free combination may be an alternative to the current standard-of-care.”

1. Burtness B, et al. Lancet. 2019;394(10212):1915–1928.
2. Guigay J, et al. Front Oncol. 2019;9:668.
3. Dzienis M, et al. Pembrolizumab (pembro) + carboplatin (carbo) + paclitaxel (pacli) as first-line (1L) therapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Phase VI KEYNOTE-B10 study. Abstract 651O, ESMO Congress 2022, 09–13 September, Paris, France.

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Posted on 17 November 202218 March 2024