Modified EXTREME regimen versus modified TPEx regimen as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, open-label, randomized, exploratory study (TEMPER study)

Abstract Background The EXTREME regimen is the standard first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), but it is poorly tolerated in Asian patients. We aimed to compare the efficacy and safety of the modified EXTREME (mEXTREME) and modified TPEx (mTPEx) regimens in Japanese patients. Methods This was a multicenter, randomized, exploratory study. The dose of chemotherapeutic agents was reduced by 25% for the mEXTREME regimen compared to the EXTREME regimen and by 20% for the mTPEX regimen compared to the TPEx regimen. Six and four cycles were repeated every 21 days for the mEXTREME and mTPEx regimens, respectively. In both regimens, weekly 250 mg/m 2 cetuximab was continued as maintenance therapy in case of disease control. Results Sixty-one patients were enrolled and assigned to the two treatment arms (30 to mEXTREME, 31 to mTPEx). Median PFS was 6.0 months and 5.3 months (p = 0.28), and median overall survival was 17.4 months and 18.7 months (p = 0.72) for the mEXTREME and mTPEx groups, respectively. Twenty-seven patients in the mEXTREME group and 29 patients in the mTPEx group had grade 3 or worse adverse events during chemotherapy (p = 0.61). Early tumor shrinkage was 20% in the mEXTREME group and 44% in the mTPEx group (p = 0.01). Conclusions No significant differences in survival were observed between the two groups, with similar toxicity profiles. As early tumor shrinkage was favorable in the mTPEx group, the mTPEx regimen may be the first-line standard of care for Asian patients with R/M HNSCC, particularly those who are not candidates for up-front pembrolizumab due to CPS < 1 or the presence of immunologically related complications and those who need rapid tumor shrinkage to relieve tumor-related symptoms. Trial registration UMIN000025436.