One of the stories that has stood out over the last few years in breast cancer treatment was the FDA’s approval in 2015 of the drug palbociclib (Ibrance) for treatment of hormone receptor-positive metastatic breast cancer (MBC). Palbociclib was the first in a category of targeted therapies called CDK 4/6 inhibitors to receive FDA approval. These therapies are used in combination with the hormone therapy fulvestrant and are now part of standard-of-care treatment for patients with hormone-receptor positive MBC.
The three CDK 4/5 inhibitors approved so far by the FDA were approved based on their ability to extend progression free survival, which refers to how long a patient lives with the disease but it does not get worse. It was believed that there would also be benefits in extending overall survival time–actually helping patients to live longer. But there wasn’t enough information available at the time of the approvals to know whether the drugs did that. Also unknown was whether these drugs could reduce the risk of recurrence in patients with early stage hormone receptor-positive breast cancer.
There’ve been some interesting developments this year in targeted treatments for hormone receptor-positive breast cancer, some of which begin to address those questions. Here are three stories that stand out so far this year, and which we’ll be continuing to follow.
CDK 4/6 Inhibitors: Extending Overall Survival
At the 2019 annual meeting of the American Society of Clinical Oncology (ASCO), the findings were presented for a large clinical trial involving premenopausal women with hormone receptor-positive MBC. Participants in the trial, which had 672 women enrolled, were randomized to receive either hormone therapy alone or hormone therapy with the addition of a CDK 4/6 inhibitor, ribociclib (Kisqali).
The results were quite significant. After three and half years, 70 percent of the patients receiving ribociclib were still alive compared to 46 percent of those who received only the hormone treatment. The study was reported in the New England Journal of Medicine.
Here are some resources for more information about the study and its implications:
- A New Option to Treat Metastatic Breast Cancer, by Dr. Deanna Attai, breast surgeon at UCLA;
- A Drug Prolonged Life in Younger Women With Advanced Breast Cancer by Denise Grady in the New York Times; and
- Addition of Ribociclib to Endocrine Therapy in Premenopausal Women With HR-Positive, HER2-Negative Breast Cancer in the ASCO Post.
CDK 4/6 Inhibitors: Clinical Trials in Early Stage Breast Cancer
Several randomized, phase III clinical trials are now looking into whether CDK 4/6 inhibitors can reduce the risk of recurrence in early stage breast cancer. Here are few of them, with links for more information.
The NATALEE trial will evaluate ribociclib and hormone therapy for treatment of stage II and stage III breast cancer. This study is currently enrolling women at any menopausal status and men who have hormone receptor-positive, HER2-negative breast cancer. Participants will be randomized to receive either hormone therapy alone or hormone therapy with the addition of ribociclib, after they have completed other therapies in their treatment plans such as radiation or chemotherapy.
The PENELOPE-B trial is comparing treatment with the CDK 4/6 inhibitor palbociclib and hormone therapy to hormone therapy alone for patients who have residual disease after completing pre-surgical chemotherapy. This study began in 2013 and is expected to have results by the end of next year.
The PALLAS trial is evaluating the addition of palbociclib to hormone therapy for patients with stage II and stage III breast cancer.
These clinical trials were discussed in a special session on treatment for hormone receptor-positive MBC at the 2019 ASCO annual meeting, which can be viewed in a webcast from Clinical Care Options. Clinical trials of CDK 4/6 inhibitors to treat early stage breast cancer are also discussed in an article in Onclive.
PI3K Inhibitors: First FDA Approval in Breast Cancer
In May of this year, the FDA approved the first in another category of targeted therapies, PI3K inhibitors, for treatment of PIK3CA-mutated hormone-receptor positive MBC. The new drug, alpelisib (Piqray) is given along with the hormone therapy fulvestrant (Faslodex). The FDA also approved a companion diagnostic test for the PIK3CA mutation.
The approval was based on findings from the randomized SOLAR-1 trial. Patients in the trial whose tumors had the mutation and received both alpelisib and hormone therapy went for a longer time without their disease progressing than those who only received the hormone therapy (a median of 11 months vs. 5.7 months.) However, the drug has significant side effects and it’s not known yet whether it actually increases overall survival time for patients.
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