Taxane-based TPEx shows promise for head, neck cancer
The taxane-based TPEx regimen demonstrated encouraging overall survival (OS) benefit for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) compared with the fluorouracil (5FU)-based EXTREME regimen, according to the results of the TPExtreme* trial presented at ASCO 2019.
The study comprised 539 participants with R/M HNSCC (median age 60 years, 87.5 percent male, 40 percent with oropharyngeal tumour) unsuitable for locoregional treatment. Participants were randomized 1:1 to receive either the TPEx (four cycles of cisplatin 75 mg/m2 and docetaxel 75 mg/m2 Q3W plus G-CSF** after each cycle, followed by weekly cetuximab maintenance [400 mg/m2 loading dose then 250 mg/m2]) or the EXTREME regimen (six cycles of cisplatin 100 mg/m2, 5FU 4,000 mg/m2 96 hours continuous infusion Q3W, then weekly cetuximab maintenance). [ASCO 2019, abstract 6002]
At 3 years, compared with EXTREME recipients, TPEx-treated participants had a numerically higher OS rate (median, 14.5 vs 13.4 months, hazard ratio [HR], 0.87, 95 percent confidence interval [CI], 0.71–1.05; p=0.15).
Despite not being statistically significant, OS rates in both arms were higher than in previous trials which showed an expected median OS of 14.0 and 10.1 months for the TPEx and EXTREME regimens, respectively, said study author Dr Joel Guigay from the Antoine Lacassagne Comprehensive Cancer Centre, FHU OncoAge, Université Côte d’Azur in Nice, France.
TPEx also had a better toxicity profile than EXTREME, with fewer grade 4/5 adverse events (36 percent vs 51 percent; p<0.001), the most common being neutropenia (24 percent vs 49 percent) and leukopenia (23 percent vs 38 percent).
The EXTREME regimen is the standard first-line treatment for R/M HNSCC. [N Engl J Med 2008;359:1116-1127] However, due to the drawbacks associated with this combination (ie, toxicity, difficult delivery of 5FU), researchers have investigated the potential of taxanes based on the promising outcomes observed with the TPEx regimen. [Ann Oncol 2015;26:1941-1947] “[T]he GORTEC TPEx trial [showed that] TPEx required fewer chemotherapy cycles and may be less toxic and more efficacious than EXTREME,” noted Guigay.
“[Our findings] confirm the good survival outcomes and response rates of the TPEx regimen observed in the first phase II study despite the lack of significant OS increase compared with EXTREME,” said Guigay. “[Therefore,] TPEx could favourably replace EXTREME as a new option for patients with first-line R/M HNSCC … with a shorter time on chemotherapy and significantly lower toxicity than the EXTREME regimen.”
However, given the lack of statistically significant OS improvement with TPEx, the findings may not be considered “practice-changing”, pointed out discussant Prof Vania Noronha from the Department of Medical Oncology of Tata Memorial Hospital in Mumbai, India.
Further investigation is thus warranted as the study failed to meet the primary endpoint of OS, noted Noronha. Moreover, TPEX was significantly toxic despite having a better safety profile, she added, noting the overall 81-percent grade ≥3 toxicity rate. “[Nonetheless,] taxanes are an important chemotherapeutic option in advanced head and neck cancer,” said Noronha.