2018 ASCO: Phase III SANDPIPER Trial Evaluates Taselisib Plus Fulvestrant in Advanced Breast Cancer
In a phase III clinical trial, the investigational PI3K inhibitor taselisib combined with standard hormone therapy fulvestrant (Faslodex) halted the growth of advanced breast cancer growth by 2 months longer than hormone therapy alone. In addition, the novel combination decreased the chance of cancer worsening by 30%. The study was featured in a press briefing today and will be presented by Baselga et al at the 2018 ASCO Annual Meeting (Abstract LBA1006).
Taselisib targets a common genetic abnormality in breast cancer—PIK3CA gene mutation—and is the first and most potent treatment in a relatively new class of PI3K inhibitors, according to the authors. It is the first drug that specifically blocks the PI3K-alpha protein, which is mutated in estrogen receptor–positive breast cancers. Taselisib has also shown promising clinical benefit in early trials of patients with head and neck cancer and certain gynecologic cancers.
“About 40% of all patients with advanced estrogen receptor–positive breast cancer have PIK3CA mutations, which means they could benefit from taselisib,” said lead author José Baselga, MD, PhD, FASCO, Physician-in-Chief at Memorial Sloan Kettering Cancer Center. “Our findings are proof that targeting this pathway in breast cancer is effective. However, 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.”
Trial Details
The SANDPIPER trial is the first and largest phase III clinical trial of taselisib, according to the authors. The study enrolled 516 postmenopausal women with locally advanced or metastatic estrogen receptor–positive, HER2-negative metastatic breast cancer that worsened or recurred despite initial hormone treatment with aromatase inhibitors. Women were randomly assigned to receive fulvestrant and placebo (176 women) or fulvestrant and taselisib (340 women).
Women who received taselisib and fulvestrant had a 30% lower chance of cancer worsening than those who received fulvestrant and a placebo, and taselisib extended the time until the cancer worsened by a median of 2 months (7.4 months with taselisib/fulvestrant vs 5.4 months with fulvestrant/placebo). The response rate to treatment was more than doubled when taselisib was added (28% vs 11.9%). Overall survival data are not yet available.
The most common severe side effects for patients who received taselisib were diarrhea, hyperglycemia, and colitis. Due to side effects, 17% of women who received taselisib stopped treatment early, compared to only 2% of those who did not receive the targeted therapy.
Next Steps
When researchers looked at outcomes by geographic area, they noted that taselisib provided more benefit to study participants who received treatment in North America and Europe, where cancer worsening was delayed by a median of 3.5 months (7.9 with taselisib/fulvestrant vs 4.5 months with fulvestrant/placebo). In other countries including Eastern Europe and Latin America, taselisib appeared to provide very little or no added benefit. More research is needed understand the reasons for this discrepancy.
Commentary
“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.
This study received funding from F. Hoffmann-La Roche Ltd.
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®.
