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Blocking a pathway causing hormonal therapy resistance may benefit women with advanced ERPR-positive breast cancer

  • Ian Krop,MD, PhD

    Adding a PI3K inhibitor to hormonal therapy for metastatic breast cancer may help overcome resistance to the hormonal therapy and delay disease progression in a subgroup of such patients, suggest results of a phase II clinical trial.

    According to data presented at the 2014 San Antonio Breast Cancer Symposium, investigators from Dana-Farber Cancer Institute provided 17-month follow up data from the first blinded and randomized clinical study evaluating a PI3K inhibitor in patients with metastatic breast cancer.

    "Overactivity of the PI3K pathway has been implicated in resistance to hormonal therapies, such as fulvestrant, in women with estrogen receptor (ER)-positive breast cancer," said Ian Krop, MD, PhD, director of clinical research for the Breast Oncology Program in the Susan F. Smith Center for Women's Cancers at Dana-Farber.

    Krop is lead investigator of the FERGI Phase II Study, in which postmenopausal patients with metastatic ER-positive breast cancer were randomized to two groups. One received fulvestrant, plus the PI3K inhibitor pictilisib. The other group received fulvestrant plus a placebo. The 168 patients included those with and without PI3K mutations. The primary endpoint was progression-free survival (PFS).

    For the cohort as a whole, addition of the PI3K inhibitor to fulvestrant delayed the progression of the cancer by 6.6 months compared to 5.1 months in the fulvestrant-plus-placebo group — a "modest benefit" that was not statistically significant, Krop said.

    There was, however, a "more substantial" improvement in the subgroup of women who were both estrogen receptor and progesterone receptor positive. Their progression-free survival was 7.4 months — double the 3.7 months of patients who did not receive the PI3K inhibitor, Krop reported. Krop is planning on investigating whether the benefit of pictilisib for women with ER/PR-positive breast cancer holds true in an additional cohort of patients within this study.

    To their surprise, the researchers found that the benefits of the added PI3K inhibitor drug were similar whether or not the patients had a mutation in the PIK3CA gene, which is a key part of the PI3K signaling pathway. "It may be that a PIK3CA mutation is not the only way to activate PI3K signaling," Krop suggested.

    Genentech, which makes pictilisib, funded the trial.

Posted on December 10, 2014

  • Ian E. Krop, MD, PhD
  • Research
  • Breast Cancer
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