First-line cisplatin, docetaxel, and cetuximab for patients with recurrent or metastatic head and neck cancer: A multicenter cohort study

Abstract

BACKGROUND The targeted therapy cetuximab [directed at the epidermal growth factor receptor (EGFR)] in combination with 5-fluorouracil and platinum-based chemotherapy (the EXTREME regimen) has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Thus, this scheme has been established as the preferred first-line option for these patients. However, more recently, a new strategy combining platinum, taxanes, and cetuximab (the TPEx regimen) has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials. AIM To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study. METHODS This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1, 2017 and April 31, 2020. Chemotherapy consisted of four cycles of docetaxel, cisplatin, and cetuximab followed by cetuximab maintenance therapy. Clinical outcomes and toxicity profiles were collected from medical charts. Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors (version 1.1). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS Twenty-four patients were included. The median age at diagnosis was 58 years (range: 36-77 years). The majority of patients (83.3%) received at least four chemotherapy cycles in the initial phase. In the included group, the overall response rate was 62.5%, and 3 patients achieved a complete response (12.5%). The median time to response was 2.4 mo [95% confidence interval (CI): 1.3-3.5]. With a median follow-up of 12.7 mo (95%CI: 8.8-16.6), the median progression-free survival (PFS) was 6.9 mo (95%CI: 6.5-7.3), and the overall survival rate at 12 mo was 82.4%. Patients with documented tumor response showed a better PFS than those with disease stabilization or progression [8.5 mo (95%CI: 5.5-11.5) and 4.5 mo (95%CI: 2.5-6.6), respectively; P = 0.042]. Regarding the safety analysis, two-thirds of patients reported at least one treatment-related adverse event, and 25% presented grade 3 toxicities. Of note, no patient experienced grade 4 adverse events. CONCLUSION TPEx was an adequately tolerated regimen in our population, with low incidence of grade 3-4 adverse events. The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination. This regimen may be considered an attractive therapeutic strategy due to its simplified administration, decreased total number of chemotherapy cycles, and treatment tolerability.

Real-world use of first-line pembrolizumab + platinum + taxane combination regimens in recurrent / metastatic head and neck squamous cell carcinoma

“…A recent clinical trial comparing cetuximab-containing regimens that included platinum and 5-FU versus cisplatin and docetaxel found that individuals treated with the taxane-containing regimen had similar overall and progression-free survival compared to those receiving the 5-FU-containing, but fewer serious adverse events and better self-reported quality of life (17). Other studies have confirmed that cetuximab + cisplatin + docetaxel is a welltolerated regimen (18,19). Further research, including the final results of the KEYNOTE-B10 clinical trial, is needed to determine whether combining pembrolizumab with taxanes is also associated with reduced toxicity compared to 5-FU-containing combinations.…”

“…These findings may be related to 5-FU's toxicity (particularly with respect to gastrointestinal side-effects) and patient inconvenience [i.e., the need for port placement and a 96-hour pump to administer the drug, and a requirement for dihydropyrimidine dehydrogenase deficiency testing before initiating treatment (12)]. Taxanes such as paclitaxel have been suggested as replacements for 5-FU in both pembrolizumab and cetuximab combination therapies for R/M HNSCC and have demonstrated encouraging performance in initial analyses (12)(13)(14)(15)(16)(17)(18)(19). Pembrolizumab in combination with cisplatin or carboplatin plus paclitaxel or docetaxel is currently listed as a category 2A option for 1L treatment of R/M HNSCC in the NCCN Guidelines ® (11), and thus is already available in the US.…”

Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer

“…A modified systemic 5-FU chemotherapy protocol was assessed with the aim of decreasing hospitalization and/or treatment time without compromising outcomes, which could increase the life quality of patients with metastatic squamous cell carcinoma of the head and neck (SCCHN) (Meirovitz et al., 2022 ). More recently, a new strategy using the immune checkpoint inhibitor pembrolizumab alone or in combination with 5-FU and platinum has become an appropriate first-line treatment for patients with recurrent or metastatic head and neck cancer (Falco et al., 2022 ). 5-FU is accessible to the relevant tissues in conjugation with the transport protein serum albumin (Chinnathambi et al., 2016 ).…”