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CHICAGO -- Cutting the duration of adjuvant trastuzumab (Herceptin) in half led to similar breast cancer control and overall survival (OS), according to a large randomized trial that could change longstanding clinical practice.

After a median follow-up of 5 years for more than 4,000 patients, 89.4% of patients randomized to 6 months of adjuvant trastuzumab remained alive without disease recurrence, as did 89.8% of those who received the current standard 12 months. The near-identical outcome more than met the 3% absolute difference established for the noninferiority of 6 versus 12 months of trastuzumab.

The shorter duration of trastuzumab treatment was associated with a 50% decrease in the number of women who discontinued treatment because of cardiac toxicity, Helena Earl, MBBS, PhD, of the University of Cambridge in England, said at a press briefing prior to the (ASCO) annual meeting.

"The first results demonstrate that 6 months of adjuvant trastuzumab is noninferior to 12 months," said Earl. "Quality of life, patient-reported experience, and health-economic assessments are ongoing."

The study "marks the first steps towards reduction of treatment duration for many women with HER2-positive breast cancer," she added.

In response to a question, Earl declined to say the results made a definitive case for a new standard of care for early HER2-positive breast cancer. She said investigators need to perform more detailed analyses of the data and then publish the findings, and breast cancer specialists need time to review the findings.

"What we're saying at the moment is that we need to have a detailed look at this group of patients," she said. "The headline result is that 6 months is as good as 12 months. This is a real-world result, but we need to be very careful and cautious about coming out at this point and saying 'Yes, 6 months is enough.'"

Principal caveats at this point are the lack of mature data on OS and results of biomarker studies, said Richard Schilsky, MD, ASCO chief medical officer.

"When looking at the results of a clinical trial, we're looking at the average results for that population of patients," he said. "Undoubtedly, there may well be some patients in the population who don't do as well with only 6 months of treatment. Dr. Earl mentioned some of the translational research is ongoing that will help identify which women might actually benefit from continuation of treatment for the full 12 months."

"I find the results quite compelling," he added. "I think it is likely that it will signal a shift, even in the U.S. oncology community, toward a shorter duration of Herceptin adjuvant therapy."

The breast cancer clinical community will likely want to see the complete data, including subgroup analyses, before deciding how the results might affect clinical practice, said Mariana Chavez MacGregor, MD, of the MD Anderson Cancer Center in Houston. The clear and consistent benefit that clinical trials have shown for 12 months of adjuvant trastuzumab will make clinicians cautious about changing clinical practice.

"In medicine, in general, I think we have a different threshold if we think we're adding something that might help our patients a little bit, but possibly taking something away from our patients, we want to be really, really sure about it," she said.

Clinical trials consistently showed a significant reduction in cancer recurrence and death in patients who received adjuvant trastuzumab for early HER2-positive breast cancer. However, the trials also showed that treatment-associated cardiotoxicity increased with duration of trastuzumab therapy, Earl noted.

Since 2005, 12 months of adjuvant trastuzumab has been standard of care for women with early HER2-positive breast cancer. One previous trial showed a similar benefit with 9 months of adjuvant therapy, providing a rationale for the randomized PERSEPHONE trial to compare 6 and 12 months of adjuvant therapy.

Following surgery for early HER2-positive breast cancer, investigators at 152 sites in England randomized 4,088 patients to receive 6 or 12 months of trastuzumab. The trial's objective was to determine whether 6 months of adjuvant therapy would lead to DFS at 4 years that was no more than 3% below the projected DFS with 12 months of adjuvant therapy.

The trial design established a DFS hazard ratio of 1.29 as the definition of noninferiority. The data after a median follow-up of 5 years yielded an HR 1.05 for 6 versus 12 months of adjuvant therapy (P=0.01).

Investigators found that 4% of patients treated for 6 months discontinued prematurely because of cardiotoxicity, as compared with 8% in the 12-month group (P<0.0001).

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