Docetaxel in combination with cisplatin and cetuximab did not significantly improve overall survival compared with platinum chemotherapy plus fluorouracil and cetuximab but maintained a favorable safety profile.
Even though treatment with docetaxel in combination with cisplatin and cetuximab, known as the TPEx regimen, did not statistically significantly improve overall survival (OS) compared with platinum chemotherapy plus fluorouracil and cetuximab (EXTREME) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), the regimen produced a more favorable safety profile, according to data published in Lancet Oncology.
Because of this safety profile, the TPEx regimen could be considered as an alternative treatment option in the first-line setting to standard-of-care EXTREME for recurrent or metastatic HNSCC, specifically for patients who are not good candidates for up-front pembrolizumab (Keytruda) therapy.
“This randomised trial confirmed the good survival results of the TPEx regimen previously observed in the initial phase 2 trial,” wrote the investigators. “Compared with the EXTREME regimen, TPEx did not show a significant benefit in overall survival but was a shorter and better-tolerated treatment regimen, and showed a better [quality of life]. The TPEx regimen might offer an alternative to the EXTREME regimen or pembrolizumab in first-line treatment of fit patients with recurrent or metastatic HNSCC.”
A total of 541 patients were enrolled and randomly assigned to receive either the TPEx treatment regimen (n = 271) or the EXTREME treatment regimen (n = 270). Median follow-up time was 34.4 months (interquartile range [IQR], 26.6-44.8) and 30.2 months (IQR, 25.5-45.3) in the TPEx and EXTREME groups, respectively.
At the point of data cutoff, 209 patients in the TPEx group and 218 patients in the EXTREME group had died. There was no statistically significant difference in terms of OS, with a median OS of 14.5 months (95% CI, 12.5-15.7) in the TPEx group and 13.4 months (95% CI, 12.2-15.4] in the EXTREME group (HR, 0.89; 95% CI, 0.74-1.08; P = .23).
Grade 3 or worse adverse events (AEs) were observed in 81% of patients in the TPEx group compared with 93% of patients in the EXTREME group (P < .0001). More, at least 1 serious AE occurred in 45% and 54% of patients in the TPEx and EXTREME groups, respectively.
A total of 16 patients in the TPEx group and 21 patients in the EXTREME group died as a result of AEs. Further, 8 and 11 patients died from causes considered to be treatment-related in the TPEx and EXTREME groups, respectively.
“Although our trial did not meet its primary end point, the results are informative and could potentially change practice, because the TPEx regimen could be an alternative to the EXTREME regimen in first-line treatment of patients with recurrent or metastatic HNSCC, especially for those with a negative PD-L1 combined positive score, those who might not be good candidates for up-front pembrolizumab because of immunologically relevant comorbidities, patients with high tumor burden or symptoms that mean a rapid response is a key treatment goal, or patients with contraindication to fluorouracil,” explained the investigators.
This multi-center, open-label phase 2 trial (NCT02268695) occurred across 68 medical centers, hospitals, and private clinics in France, Spain, and Germany. Patient eligibility required histologically confirmed, recurrent or metastatic HNSCC in those between ages 18 and 70 years who had an ECOG performance status of 1 or less.
The primary end point of the research was OS observed in the intent-to-treat population. The safety profile was also analyzed for patients who received at a minimum of 1 dose of chemotherapy or cetuximab.
Since the research was conducted prior to the introduction of immunotherapy as treatment for HNSCC, the data reflects the EXTREME treatment regimen as the standard of care, which is no longer the case. The research team notes that, “however, pembrolizumab alone or combined with platinum–fluorouracil is not available for all patients with recurrent or metastatic HNSCC and is not beneficial to all patients.”
Guigay J, Auperin A, Fayette J, et al. Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2021;22(4):463-475. doi:10.1016/S1470-2045(20)30755-5