Adding pertuzumab to an adjuvant regimen of trastuzumab for women with early-stage HER2+ breast cancer reduces the risk of disease recurrence, especially among those with node-positive and hormone receptor–negative disease. Results from the phase III APHINITY trial, which could help pertuzumab earn full approval for this indication, were presented at the 2017 American Society of Clinical Oncology Annual Meeting.

Women with HER2+ early-stage breast cancer stand to benefit from treatment with two HER2-targeted agents after surgery—although the addition of pertuzumab (Perjeta; Genentech) to standard-of-care trastuzumab (Herceptin; Genentech) lowers the risk of recurrence by only around 1% over 3 years. That's according to a 3-year analysis of the phase III APHINITY trial presented on June 5 at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, and published concurrently in The New England Journal of Medicine (N Engl J Med 2017 June 5 [Epub ahead of print]).

The addition of pertuzumab “is potentially practice-changing for those at the highest risk of relapse,” said Neelima Denduluri, MD, a breast oncologist at the Virginia Cancer Specialists in Arlington, who chairs the ASCO Clinical Practice Guidelines Committee and serves as the associate chair of breast cancer oncology for The US Oncology Network.

Yet, for her, the main take-home message of APHINITY has less to do with the experimental combo and more to do with standard of care. “Trastuzumab is such a good drug in itself that not every early breast cancer patient with HER2+ disease needs combination therapy,” said Denduluri, who was not involved in the trial.

Genentech was required to run APHINITY as a condition of the FDA's accelerated approval of pertuzumab in 2013 for patients with early-stage breast cancer. In the study, clinicians randomly assigned 4,805 patients whose HER2+ breast tumors were surgically removed by lumpectomy or mastectomy to receive six to eight cycles of chemotherapy plus 1 year of trastuzumab and either pertuzumab or placebo delivered intravenously every 3 weeks.

Three years out, 5.9% of patients given pertuzumab had developed invasive breast cancer, compared with 6.8% of those who received the placebo. Rates of heart failure, a known side effect of these drugs, were low with both treatments—0.7% and 0.3% in the pertuzumab and placebo groups, respectively, a nonsignificant difference—although severe diarrhea was more common among those taking pertuzumab.

“This is a clinically meaningful result for many patients who have HER2+ breast cancer,” remarked Harold Burstein, MD, PhD, of Dana-Farber Cancer Institute in Boston, MA. “Having said that, I think it's fair to say that to get the most value out of a drug like this, we're going to be wanting to use it particularly in the patients where there is the most signal of benefit.”

Looking at subgroup analyses, trial investigators—led by Gunter von Minckwitz, MD, PhD, president of the German Breast Group in Neu-Isenburg, Germany—found that patients whose cancer had spread to the lymph nodes or who had hormone receptor–negative disease had the largest increase in invasive disease–free survival (IDFS) when given the dual HER2-blocking therapy. “Continued follow-up of up to 10 years is planned and is important to assess overall survival, longer-term IDFS, and safety analysis,” von Minckwitz said.

Genentech will discuss the findings with the FDA in hopes of securing a full approval for pertuzumab to treat early-stage disease. –Elie Dolgin

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