PERSEPHONE: 4-Year Disease-Free Survival With 6 vs 12 Months of Adjuvant Trastuzumab for HER2-Positive Breast Cancer
The 4-year disease-free survival results of the UK phase III PERSEPHONE trial, reported by Earl et al in The Lancet, found that 6 months of adjuvant trastuzumab was noninferior to 12 months when given with chemotherapy in HER2-positive early breast cancer.
Study Details
The open-label trial included 4,089 patients from 152 sites in the UK. They were randomly assigned between October 2007 and July 2015 to receive 6 months (n = 2,044) or 12 months (n = 2,045) of trastuzumab in concurrent or sequential combination with anthracycline-, taxane-, or anthracycline- and taxane-based chemotherapy as stratification factors. Trastuzumab was given every 3 weeks at a loading dose of 8 mg/kg intravenously (IV) followed by maintenance doses of 6 mg/kg IV or 600 mg subcutaneously.
The primary endpoint was disease-free survival in the intent-to-treat population with a noninferiority margin of 3% for 4-year disease-free survival.
Disease-Free Survival
Median follow-up was 5.4 years, during which a disease-free survival event occurred in 13% of the 6-month group and 12% of the 12-month group. Disease-free survival at 4 years was 89.4% vs 89.8% (hazard ratio = 1.07, 90% confidence interval = 0.93–1.24, noninferiority P = .011, superiority P = .42), establishing noninferiority of the 6-month treatment. During the 5.4-year follow-up, death occurred in 9% of the 6-month group and 8% of the 12-month group.
Toxicity
Severe adverse events (grade 3 or 4 events or grade 2 palpitations) occurred in 19% of patients in the 6-month group vs 24% of the 12-month group (P = .0002). Clinical cardiac dysfunction occurred in 8% vs 11%. Overall, 3% vs 8% of patients permanently stopped trastuzumab due to cardiotoxicity (P < .0001). No cardiac deaths were considered related to trastuzumab.
The investigators concluded, “We have shown that 6-month trastuzumab treatment is noninferior to 12-month treatment in patients with HER2-positive early breast cancer, with less cardiotoxicity and fewer severe adverse events. These results support consideration of reduced-duration trastuzumab for women at similar risk of recurrence as to those included in the trial.”
Helena Earl, MBBS, of the Department of Oncology, Addenbrooke’s Hospital, Cambridge, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the UK National Institute for Health Research, Health Technology Assessment Programme. For full disclosures of the study authors, visit thelancet.com.
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