CDK4/6 Inhibitors in the Spotlight
The latest advances in breast cancer research were recently announced at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting. We spoke with experts Dr. Sherene Loi, Ph.D., medical oncologist and professor of medical oncology at the Peter MacCallum Cancer Centre, and Dr. Erika Hamilton, M.D., medical oncologist at the Sarah Cannon Research Institute, about some of the new breakthroughs announced at ASCO that could impact patient care.
One of the most highly anticipated trials at ASCO this year was the NATALEE trial, which focused on improving treatments for patients with early estrogen receptor-positive (ER+) breast cancer at risk for recurrence after receiving standard hormone therapy. Researchers found that adding a CDK4/6 inhibitor called ribociclib to hormonal therapy decreased the risk of recurrence by 25%.
As Dr. Loi explains, this is a great win for patients. “This was a positive study in that the combination of CDK4/6 inhibitor improved the risk of recurrence compared with hormone therapy alone,” she says. “This is great for the field because the CDK4/6 inhibitors have been around a long time in the metastatic setting and have improved overall survival.”
While these results are exciting, this is early data, and there is still more to learn about which patients would benefit the most from this additional treatment.
One featured trial, the phase 3 SONIA trial, focused on identifying the best time in treatment to use CDK4/6 inhibitors. CDK4/6 inhibitors are often used to treat metastatic ER+ breast cancer, but there are no studies that address whether these treatments should be used as first-line or second-line therapy to achieve the best outcomes for patients. This trial sparked some controversy at ASCO, as the results sparked more questions than answers.
SONIA trial participants were divided into two groups: One group received a CDK4/6 inhibitor treatment with hormone therapy first, and the other group received a CDK4/6 inhibitor plus hormone therapy later after their disease had progressed. The groups had no differences in outcomes, but patients who took CDK4/6 inhibitors as a second-line therapy did not need to take them for as long as those who took them as a first-line therapy. As a result, patients who took the treatment later had fewer side effects and experienced significant savings in the cost of treatment.
Despite promising results, some oncologists had concerns about these findings. As Dr. Hamilton explains, “I don’t think this is necessarily going to be practice-changing in the United States. I think it may be in countries where they have less access to drugs, where the cost of care is a really big issue and can really determine approval and reimbursement strategies. But I’m not 100% sold, based on this trial, that we should not be continuing to give CDK4/6 inhibitors upfront in the first-line setting.” Komen will be keeping an eye on future trials that will help identify the ideal treatment strategy timing.
New Treatments and Targets on the Horizon
Other exciting announcements at ASCO focused on new treatment strategies and targets for patients. While there are several treatments available targeting HER2, there are currently no FDA-approved treatments that target a related protein called HER3. Researchers are interested in targeting the HER3 protein because it’s associated with aggressive breast cancer. The HER3-DXd trial, led by Dr. Hamilton, is evaluating a new antibody-drug conjugate (ADC), called patritumab deruxtecan (HER3-DXd), that may offer a new treatment option to patients with HER3-expressing MBC. As Dr. Hamilton shared at ASCO, the overall response rate to this new treatment was 35%.
As Dr. Hamilton explains, “The main takeaways from our data with patritumab deruxtecan, or HER3-DXd, really was that overall response rate and the clinical benefit rate looked encouraging across both HR+ and triple negative breast cancer (TNBC).”
Another trial that offered promising results was the PHERGain Trial, which was designed to de-escalate chemotherapy for HER2+ patients. Using non-invasive imaging, researchers determined if patients responded to anti-HER2 therapy prior to surgery, and if so, they did not receive post-surgery chemotherapy. Results of the PHERGain trial showed that the patients who skipped chemotherapy still had good outcomes while avoiding the side effects of chemotherapy.
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