In a phase II trial (GORTEC 2014-01 TPExtreme) reported in The Lancet Oncology, Joël Guigay, MD, and colleagues found that first-line TPEx (docetaxel/platinum/cetuximab) did not improve overall survival vs the standard-of-care EXTREME regimen (fluorouracil [5-FU]/platinum/cetuximab) in patients with recurrent or metastatic head and neck squamous cell carcinoma. However, the TPEx regimen was associated with a more favorable safety profile.
Joël Guigay, MD
Study Details
The open-label trial included 541 patients with disease unsuitable for curative treatment from sites in France, Spain, and Germany. They were randomly assigned between October 2014 and November 2017 to receive either the TPEx (n = 271) or EXTREME (n = 270) regimens.
TPEx consisted of docetaxel at 75 mg/m² and cisplatin at 75 mg/m² on day 1 and cetuximab on days 1, 8, and 15 (400 mg/m² on day 1 of cycle 1, and 250 mg/m² weekly thereafter) every 21 days for four cycles, with systematic granulocyte colony–stimulating factor (G-CSF) support at each cycle. If disease control was achieved after four cycles, cetuximab at 500 mg/m² was continued every 2 weeks until disease progression or unacceptable toxicity.
The EXTREME regimen consisted of 5-FU at 4,000 mg/m² on days 1 to 4; cisplatin at 100 mg/m² on day 1; and cetuximab on days 1, 8, and 15 as above every 21 days for six cycles, with weekly cetuximab at 250 mg/m² maintenance in patients with disease control; G-CSF support was not mandatory.
The primary endpoint was overall survival in the intention-to-treat population.
Overall Survival
Median follow-up was 34.4 months (interquartile range [IQR] = 26.6–44.8 months) in the TPEx group and 30.2 months (IQR = 25.5–45.3 months) in the EXTREME group. Median overall survival was 14.5 months (95% confidence interval [CI] = 12.5–15.7 months) in the TPEx group vs 13.4 months (95% CI = 12.2–15.4 months) in the EXTREME group (hazard ratio [HR] = 0.89, 95% CI = 0.74–1.08, P = .23).
Median progression-free survival was 6.0 months (95% CI = 5.7–6.4 months) in the TPEx group vs 6.2 months (95% CI = 5.8–6.7 months) in the EXTREME group (HR = 0.88, 95% CI = 0.74–1.04, P = .14). Rates of objective response on independent central review at 12 weeks among 190 vs 179 patients were 57% (including complete response in 4%) vs 59% (including complete response in 6%, P = .89).
The planned number of treatment cycles was received by 72% vs 44% of patients (P < .0001). Cetuximab maintenance therapy was started by 72% vs 52% of patients (P < .0001), with the primary reasons for not starting being adverse events and disease progression.
KEY POINTS
- The TPEx regimen did not improve overall survival vs the EXTREME regimen.
- TPEx was associated with reduced severe toxicity.
Adverse Events
Grade ≥ 3 adverse events occurred in 81% of patients in the TPEx group vs 93% of the EXTREME group (P < .0001), with grade ≥ 4 events occurring 36% vs 52%. The most common grade ≥ 3 adverse events were hematologic events and electrolyte disturbances in both groups, including neutropenia (25% vs 49%), leukopenia (23% vs 38%), thrombocytopenia (2% vs 20%), anemia (8% vs 20%), kalemia disorder (10% vs 23%), and magnesemia disorder (13% vs 22%).
Serious adverse events occurred in 45% vs 54% of patients. Adverse events led to death in 16 vs 21 patients, with death considered related to treatment in 8 patients vs 11 patients; treatment-related deaths were most commonly due to sepsis or septic shock (4 patients in each group).
The investigators concluded, “Although the trial did not meet its primary endpoint, with no significant improvement in overall survival with TPEx vs EXTREME, the TPEx regimen had a favorable safety profile. The TPEx regimen could provide an alternative to standard of care with the EXTREME regimen in the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma, especially for those who might not be good candidates for upfront pembrolizumab treatment.”
Dr. Guigay, of the Department of Medical Oncology, Centre Antoine Lacassagne, Nice, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Santé and Chugai Pharma. For full disclosures of the study authors, visit thelancet.com.
