Shorter trastuzumab treatment as effective for HER2-positive breast cancer, with less cardiac toxicity
Results of the phase III, randomized PERSEPHONE trial indicate that 6 months of trastuzumab treatment is non-inferior to the current standard 12-month regimen in patients with HER2-positive early breast cancer. After 4 years, the disease-free survival (DFS) was similar in both study arms at 89.4% with the 6-month regimen and 89.8% in patients receiving trastuzumab for 12 months. Moreover, only 4% of women in the 6-month arm stopped trastuzumab early because of cardiac problems, compared to 8% in the 12-month arm.
Adjuvant trastuzumab has significantly improved the outcomes for HER2-positive early breast cancer patients. Based on the pivotal registration trials with trastuzumab in this setting, 12 months of adjuvant trastuzumab quickly became standard of care. Unfortunately, cardiac toxicity has always been a concern in women treated with trastuzumab. In fact, in the HERA trial, 5.2% of patients randomised to receive 12 months of trastuzumab had to stop therapy early due to heart problems. A shorter duration could reduce this toxicity and also reduce costs. In this respect, a small trial in Finland (FinHer) reported similar benefit from as little as 9 weeks of trastuzumab.
In the phase III PERSEPHONE study, 4,089 women with HER2-positive early breast cancer were randomised between 6 and 12 months of trastuzumab. Women also received chemotherapy (anthracycline-based, taxane-based, or a combination of both) while enrolled in the trial. The non-inferiority design allowed the trial to help determine whether reduced duration of treatment can be as good as the standard treatment within pre-specified limits, which are set before the trial starts. The primary endpoint of the study was DFS. In addition to this, the study also evaluated the cardiac left ventricular ejection fraction (LVEF), the quality of life of patients and evaluated the financial implications of shortening the trastuzumab duration.
The women in the trial were followed for a median of over five years. Researchers found that 89.4% of women in the 6-month arm and 89.8% in the 12-month arm were alive and free of breast cancer at four years. As such, the trial demonstrated that 6 months of trastuzumab treatment was non-inferior to 12 months (HR[95%CI]: 1.05[0.88–1.25], non-inferiority demonstrated as HR <1.29). Only 4% of women who received trastuzumab for 6 months had to stop treatment early due to heart problems, compared to 8% of those who took trastuzumab for 12 months (p< 0.0001). Moreover, patients in the 6-month arm also had a more rapid recovery of their cardiac function. The impact of treatment length on quality of life is currently being evaluated with qualitative feedback from trial participants. A detailed cost-effectiveness analysis is also underway.
Earl H, et al. PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): Randomised phase 3 non-inferiority trial with definitive 4-year (yr) disease-free survival (DFS) results. Presented at ASCO 2018; Abstract 506.