Less toxic TPEx regimen possible new option for patients in first-line recurrent/metastatic head and neck squamous cell carcinoma
A randomized trial testing the TPEx regimen (docetaxel-cisplatin-cetuximab) against the standard EXTREME regimen (5-FU-platinum-cetuximab) showed encouraging survival results of the TPEx regimen. The investigators argue that the taxane-based TPEx regimen, with a shorter time on chemotherapy and significantly lower toxicity than the EXTREME regimen, could be a new first-line option in the treatment of recurrent/metastatic head and neck squamous cell carcinoma.
Background
Standard systemic treatment in first-line recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been the EXTREME regimen. In 2015, promising results from the GORTEC phase II trial were published. TPEx showed a median overall survival of 14.0 months.1 The taxane-based TPEx requires less chemotherapy cycles and may be less toxic and more efficacious that EXTREME. The role of taxane instead of 5-FU in this setting remained to be confirmed by comparing TPEx to the reference EXTREME regimen.
Trial set-up
The TPExtreme study enrolled R/M HNSCC patients (18-70 years) not suitable for locoregional treatment, with performance status 0-1, a creatinine clearance >60 ml/min, prior cisplatin ≤300 mg/m2 and no anti-EGFR for 1 year.2 Patients were randomised (1:1) to the reference EXTREME (6 cycles Q3W; maintenance cetuximab 250 mg/m2/week; N=270) or to the TPEx regimen (4 cycles Q3W; maintenance cetuximab 500 mg/m2/2 weeks; N=269). Cetuximab maintenance treatment was given until progression or unacceptable toxicity. Primary endpoint was overall survival. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) at 12 weeks, tolerance and compliance.
Results
The median follow-up of the patients was 31.6 months (EXTREME) and 32.6 months (TPEx). Median OS was 14.5 months in the TPEx arm and 13.4 months in the EXTREME arm. Hazard ratio of TPEx vs EXTREME was 0.87 (95% CI 0.71-1.05; p=0.15). The investigators attribute this lack of significance to a higher than expected OS in the reference group, causing a decrease in the trial power. No statistically significant difference for PFS was found either, with for both arms a value of ~6 months. Hazard ratio was 0.88 (95% CI 0.74-1.06; p=0.17). The ORR at 12 weeks was 46% in the TPEx arm and 40% in the EXTREME arm.
The percentage of patients with no adverse events or grade 1-2 adverse events was 8% in the EXTREME arm and 19% for TPEx. With EXTREME 51% of patients had adverse events grade ≥4, compared to 36% in the TPEx arm (p<0.001). The toxicity profile was as expected. Most frequent grade ≥3 adverse events included neutropenia (EXTREME 49%, TPEx 24%), leukopenia (EXTREME 38%, TPEx 23%), magnesium disorder (EXTREME 22%, TPEx 13%) and vomiting (EXTREME 11%, TPEx 4%). Regarding compliance, in the EXTREME arm 44% of patients received all chemotherapy cycles, compared to 72% with TPEx. Delays in administration were more frequent in the reference arm (27% vs 10%).
Conclusions
This large trial confirmed the promising survival results of the TPEx regimen observed in the first phase II trial. No significant improvement in OS was observed. Despite lack of significant OS increase, taxane-based TPEx regimen comes with a shorter time on chemotherapy and was associated with less toxicity than the EXTREME treatment. Therefore, Guigay concluded that TPEx will be a viable option in first-line treatment of R/M HNSCC patients.
References
1. Guigay J, Fayette J, Dillies AF, et al. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol 2015;26:1941-7.
2. Guigay J, Fayette J, Mesia R, et al. TPExtreme randomized trial: TPEx versus Extreme regimen in 1st line recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Presented at ASCO 2019; abstract 6002.
