Adjuvant trastuzumab duration trials in HER2 positive breast cancer – what results would be practice-changing? Persephone investigator questionnaire prior to primary endpoint results

Abstract Background Twelve months treatment is the current standard of care for adjuvant trastuzumab in patients with HER2 positive early breast cancer however the optimal duration is not known. Persephone is a non-inferiority randomised controlled trial comparing 6- to 12-months of trastuzumab. In this trial there will be a trade-off between a possible small decrease in disease-free survival (DFS) with 6-months and reduced cardiotoxicity and cost. Methods A structured questionnaire asked clinicians who had recruited patients into the Persephone trial about their prior beliefs with regards to the clinical effectiveness of trastuzumab and cardiotoxicity profile, in the comparison of 6- and 12-month durations. Results Fifty-one clinicians from 40 of the 152 Persephone sites completed the questionnaire. 30/50 responders (60%) believed that 6-months trastuzumab would give the same 4-year DFS rate as 12-months trastuzumab, with 21/50 (42%) holding this belief across all breast cancer subsets. In addition, 46/49 responders (94%) reported expecting to change their clinical practice to 6-months, with their prior beliefs (most commonly 85% 4-year DFS rate with 6-months) being greater than their lowest acceptable rate (most commonly 83% 4-year DFS rate with 6-months). Low levels of cardiotoxicity were expected with both 6 and 12-months trastuzumab, with the majority expecting lower levels with 6-months. With increasing hypothesised differences of cardiotoxicity rates between the two durations, significantly lower levels of 4-year DFS with 6-months trastuzumab were deemed acceptable (p