Breast Cancer : New Research : Dr. Nilesh D. Mehta

A NEW WEAPON AGAINST BREAST CANCER : Taselisib

There is good news for patients with breast cancer. At the recent American Society of Clinical Oncology meeting in Chicago, clinical data of a new targeted drug taselisib was presented which showed some exciting results. In this clinical trial known as SANDPIPER Trial funded by from F. Hoffmann-La Roche, when taselisib was combined with standard hormone therapy fulvestrant (Faslodex), the combination halted the growth of advanced breast cancer growth by 2 months longer than hormone therapy alone, and decreased the chance of cancer worsening by 30%. Taselisib targets a genetic abnormality (PIK3CA gene mutation) within breast cancer cells. This group of emerging drugs are called as PI3K inhibitors and taselisib represents the first and most potent treatment in this class. Taselisib is the first medicine that specifically blocks the type of PI3K protein (PI3K alpha) that is mutated in estrogen receptor-positive breast cancers. This drug is also being actively studied in other cancers notably gynecologic cancer and head and neck.

“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. “Our findings are proof that 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.” 

The SANDPIPER trial, a phase III clinical trial, 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. Aromatase inhibitors are oral drugs that are typically utilized initially to treat women with breast cancer. However, tumors become smarter by developing resistance to this therapy when aromatase inhibitors are used as single drugs. Hence the combination of drugs is being increasingly utilized to circumvent resistance.

Breast cancer patients were randomly assigned to receive fulvestrant and placebo or fulvestrant and taselisib to figure out the impact of this new drug in this disease. 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 two months (7.4 months with taselisib and fulvestrant vs. 5.4 months with fulvestrant and placebo). The response rate to treatment (tumor shrinkage) was more than doubled when taselisib was added (28% vs. 11.9%). Whether women lived longer with the double drug combination or not is still not known. One of the unusual aspects of this trial was the discrepancy in results based on geographic areas. It was noted that taselisib provided more benefit to breast cancer patients who received treatment in North America and Europe, where cancer worsening was delayed by a median of 3.5 months. In other countries including Eastern Europe and Latin America, taselisib appeared to provide very little or no added benefit. More research is needed to understand the reasons for this geographic discrepancy. 

The most common severe side effects for patients who received taselisib were diarrhea, high blood sugar, and colon inflammation (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. 

A few years ago, another group of drugs known as Cyclin dependent kinase inhibitors were shown to be successful in breast cancer patients when they were combined with hormonal therapy for breast cancer. While this new combination of taselisib and hormonal therapy may not represent a home run in breast cancer treatment, it certainly opens up a new avenue of treatment option for breast cancer patients who are hormone receptor positive.

Dr. Nilesh D. Mehta
HiINDiA