Lessons Learned from De-escalation trials in favorable risk HPV-associated Squamous Cell Head and Neck Cancer - A Perspective on future trial designs.

Lessons Learned from De-escalation trials in favorable risk HPV-associated Squamous Cell Head and Neck Cancer - A Perspective on future trial designs. Clin Cancer Res. 2019 Sep 16;: Authors: Ventz S, Trippa L, Schoenfeld JD Abstract In recent years several clinical studies have investigated de-intensified treatments in HPV-associated head and neck squamous cell carcinoma. Two large Phase III trials, RTOG-1016 and De-ESCALaTE, which attempted to reduce toxicity by replacing radiotherapy (RT) in combination with cisplatin with the use of cetuximab in combination with RT, recently suggested that RT+cetuximab leads to inferior survival compared to standard therapy (observed hazard ratios of 1.45 and 5 in RTOG-1016 and De-ESCALaTE). These unexpected results should prompt a careful examination of de-intensification trials, both in HPV-associated oropharyngeal cancer and in other contexts. Statistical designs for de-intensification studies should be consistent with the study aims of reducing toxicities while maintaining survival nearly identical to the standard of care. We suggest criteria to design future de-Intensification trials and discuss important operating characteristics, including tradeoffs between power and stringent early stopping rules to reduce the number of patients exposed to inferior treatments. Using retrospective analyses of previous clinical studies, we compared designs with different operating characteristics. As an exam...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research