Abstract
BackgroundTwelve 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.MethodsA 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.ResultsFifty-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 < 0.0001).ConclusionMost responders believe that 6-months trastuzumab is adequate, both overall and within each subset of breast cancer, and plan to change their clinical practice if the Persephone results support their prior belief. An individual patient meta-analysis of the duration trials would give greater precision to estimates of the differences in efficacy and toxicity, and adequate statistical power to establish a 2% level of non-inferiority for 6-months adjuvant trastuzumab.
Highlights
Twelve months treatment is the current standard of care for adjuvant trastuzumab in patients with HER2 positive early breast cancer the optimal duration is not known
Perceptions of 4-year disease-free survival (DFS) When asked about their perceptions of 4-year DFS with 6-months trastuzumab, 60% of responders (30 of the 50 who responded to this question), believed it to be 85%, with responses ranging between 80 and 88% (Fig. 1a)
The remaining 94% have a prior belief that 6-months trastuzumab delivers appropriate levels of DFS and are waiting for the evidence to be strong enough to be able to change their clinical practice
Summary
Twelve months treatment is the current standard of care for adjuvant trastuzumab in patients with HER2 positive early breast cancer 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. Adjuvant trastuzumab treatment is proven to improve disease-free survival (DFS) and overall survival (OS) in HER2 positive early breast cancers. Investigation is still ongoing into shorter durations of adjuvant trastuzumab that could potentially provide an optimal balance between efficacy, cost and cardiac / other toxicity. The Persephone trial, completed target recruitment of 4000 patients in July 2015 and the primary endpoint results of DFS non-inferiority in an event-driven analysis are expected by June 2018
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