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Study Finds No Benefit of Adding Pictilisib to Fulvestrant in Aromatase Inhibitor–Resistant Breast Cancer

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Key Points

  • The addition of pictilisib to fulvestrant did not improve progression-free survival vs placebo in women with estrogen receptor–positive, HER2-negative, aromatase inhibitor–resistant advanced breast cancer.
  • Pictilisib is no longer being developed in this setting.

Adding the PI3K inhibitor pictilisib to fulvestrant (Faslodex) did not improve progression-free survival in women with estrogen receptor–positive, HER2-negative, aromatase inhibitor–resistant advanced breast cancer, according to the phase II FERGI trial reported in The Lancet Oncology by Krop et al. PI3K inhibition is being investigated as an approach to overcome resistance to endocrine therapy.

Study Details

The double-blind study included patients from 123 sites in 21 countries. In part 1 of the study, 168 patients with or without PIK3CA mutations were randomized to receive pictilisib (n = 89) or placebo (n =79). In part 2 of the study, 61 patients with mutations were randomized to receive pictilisib (n = 41) or placebo (n = 20). Treatment consisted of daily oral pictilisib (340 mg in part 1 and 260 mg in part 2) or placebo starting on day 15 of cycle 1, plus intramuscular fulvestrant at 500 mg on days 1 and 15 of cycle 1 and day 1 of subsequent cycles in both groups.

Progression-Free Survival

In part 1, median progression-free survival was 6.6 months in the pictilisib group vs 5.1 months in the placebo group (hazard ratio [HR] = 0.74, P = .096), including 6.5 vs 5.1 months (HR = 0.73, P = .268) among those with PIK3CA mutations and 5.8 vs 3.6 months (HR = 0.72, P = .23) among those without mutations.

In part 2, median progression-free survival was 5.4 months vs 10.0 months (HR = 1.07, P = .84).

Dosing Limited by Toxicity

In part 1, grade ≥ 3 adverse events occurred in 61% of the pictilisib group vs 28% of the placebo group, with serious adverse events reported in 16% vs 1%, respectively. Adverse events led to dose reduction of the study drug in 24% vs 1% and discontinuation of treatment in 22% vs 5%. Adverse events leading to discontinuation of pictilisib in more than one patient in part 1 were rash, pneumonitis, diarrhea, abdominal pain, stomatitis, and elevated alanine transaminase or aspartate transaminase.

In part 2, grade ≥ 3 adverse events occurred in 36% of the pictilisib group vs 37% of the placebo group, with serious adverse events in 5% vs 5%, respectively. Adverse events led to dose reduction in 17% vs 11% and treatment discontinuation in 24% (most commonly diarrhea and rash) vs 5%, respectively.

The investigators concluded: “Although addition of pictilisib to fulvestrant did not significantly improve progression-free survival, dosing of pictilisib was limited by toxicity, potentially limiting its efficacy. For future assessment of PI3K inhibition as an approach to overcome resistance to hormonal therapy, inhibitors with greater selectivity than that of pictilisib might be needed to improve tolerability and potentially increase efficacy. No further investigation of pictilisib in this setting is ongoing.”

The study was funded by F. Hoffmann-La Roche.

Ian E. Krop, MD, of Dana-Farber Cancer Institute, Boston, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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