Shortening the duration of adjuvant trastuzumab (Herceptin) therapy for early-stage HER2+ breast cancer from the current standard of 12 months to 6 months yields similar efficacy but halves the incidence of cardiac toxicity, the PERSEPHONE trial found.
“In 2005, trastuzumab was licensed with a standard of three weekly injections for 12 months, and this was the duration used empirically in pivotal registration studies,” lead study author Helena Earl, MD, professor of clinical cancer medicine at the University of Cambridge, England, said in a press briefing leading up to the annual meeting of the American Society of Clinical Oncology.
However, cardiac toxicity has been particularly problematic with this regimen. Furthermore, the Fin-HER trial, while small, suggested that only 9 weeks of adjuvant trastuzumab was possibly as efficacious (N Engl J Med. 2006 Feb;354[8]:809-20).
Dr. Earl and her coinvestigators enrolled in their phase 3 noninferiority, randomized, controlled trial 4,089 women with early-stage HER2+ breast cancer, randomizing them to either 6 months or 12 months of trastuzumab, mapped onto standard U.K. real-world practice.
The main findings showed that the 4-year rate of disease-free survival, the trial’s primary endpoint, was nearly 90% in both groups, with the absolute difference of just 0.4% falling well within the predefined 3% margin for noninferiority.
Moreover, the rate of stopping trastuzumab because of cardiotoxicity was half as high with the shorter-duration therapy; patients in that arm had more rapid recovery of cardiac function, too.
“The PERSEPHONE trial’s first results demonstrate that 6 months of adjuvant trastuzumab is noninferior to 12 months; 6 months, compared with 12 months, of treatment reduces cardiac and other toxicities and costs both to patients and health care systems,” Dr. Earl summarized. “We are confident [these results] will mark the first steps towards reduction of treatment duration for many women with HER2+ breast cancer.”
The investigators are still analyzing quality of life, patient-reported outcomes, and health economic data, she said. In addition, they are performing translational studies to look for biomarkers that may identify subgroups who fare better with one or the other duration of trastuzumab.