SANDPIPER: First Trial to Show Modest Benefit of Taselisib in Postmenopausal Women With ER+/HER- Advanced Breast Cancer

For the first time a phosphatidylinositol 3-phosphate (PI3K) inhibitor, taselisib, has been reported to provide progression-free survival benefits for patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer with PI3 kinase mutation in the catalytic subunit (PI3KCA-MUT).

These data from the phase 3, double-blind, placebo-controlled, randomized SANDPIPER study were reported at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.¹

“About 40% of all patients with advanced breast cancer estrogen receptor positive have PIK3CA mutations, which means they could benefit from taselisib,” said lead study author José Baselga, MD, PhD, FASCO, the Physician-in-Chief at Memorial Sloan Kettering Cancer Center in New York, in an ASCO press release.²

“Our findings are proof that that targeting this pathway in breast cancer is effective,” he added.

The study randomly assigned 516 patients to receive either taselisib and fulvestrant (340 patients) or placebo and fulvestrant (176 patients).

Taselisib was given at an oral daily dose of 4 mg. All patients received fulvestrant 500 mg daily.

For the primary endpoint, median progression-free survival (PFS) was 7.4 months with taselisib compared with 5.4 months with placebo. With a hazard ratio of 0.70, patients receiving taselisib were at a 30% reduced risk for disease progression (P = .0037).

At the press conference Dr Baselga also shared PFS data by geographic regions. He noted the PFS benefit was seen more in Europe and North America than in the rest of the world. Median PFS with taselisib for patients in Europe and North America was 7.9 compared with 4.5 months with placebo. With a hazard ratio of 0.57, taselisib was associated with a significantly 43% reduced risk for disease progression. For the rest of the world, median PFS was 7.4 months for patients receiving taselisib or placebo. The reason for this discrepancy is currently not understood.

For patients with measurable disease (264 patients on taselisib and 134 patients on placebo), patients on taselisib reported significantly higher objective response rates: 28% vs 11.9% for placebo; P = .0002). Duration of response was also longer for patients on taselisib: 8.7 months compared with 7.2 months for placebo.

This is because patients on taselisib had a significantly higher risk for serious adverse events (AEs): 32% compared with 8.9% for placebo. Incidence of grade 3/4 AEs were also higher with taselisib: 49.5% compared with 16.4% for placebo.

Gastrointestinal toxicities especially diarrhea (60.1% vs 19.7% for placebo) and hyperglycemia (40.4% vs 9.4% for placebo) were the more common and frequent side effects with taselisib.

AEs leading to treatment discontinuations (17% vs 2% for placebo) or dose reductions (37% vs 2%) were also higher with taselisib.

“The benefit to patients was more modest than we had hoped for, and there is a risk of considerable side effects with the addition of taselisib,” Dr Baselga said at a press conference. Taselisib has a challenging tolerability profile due to frequency of discontinuations, he pointed out.

“We now know that it’s possible to target this common breast cancer mutation, and it’s heartening to see that a new therapy can provide some benefits to women with advanced breast cancer. However, because the treatment has side effects, doctors will have to weigh its benefits and risks with their patients,” said ASCO Expert Harold Burstein, MD, PhD, FASCO, in an ASCO statement.

Taselisib is currently not approved for the treatment of ER+/HER– advanced breast cancer.

Read more of Cancer Therapy Advisor‘s coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

1. Baselga J, Dent SF, Cortés J, et al. Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA-mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER. J Clin Oncol. 2018: 36, (suppl; abstr LBA1006). Presented at 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.
2. American Society of Clinical Oncology. New Targeted Therapy Slows Growth of Advanced Breast Cancer [press release]. June 2, 2018.