New Treatment In the Works May Give Advanced Breast Cancer Patients 11 More Months Before the Disease Worsens

CDK4/6 inhibitors are targeted drugs that can be used for women with a common type of breast cancer: hormone receptor-positive and HER2-negative. These medicines interrupt the process through which breast cancer cells divide and multiply. They target specific proteins known as the cyclin-dependent kinases 4 and 6, abbreviated as CDK4/6, which are crucial in cell division and growth. Therefore, they are often referred to as targeted therapies.

Dr. Rachel Layman, professor of breast medical oncology at MD Anderson Cancer Center and a co-author of VIKTORIA-1, idea behind gedatolisib is to block more parts of the cancer growth pathway at once, so the “growth signals” that tell cancer cells to keep dividing are suppressed more.

“What is different about this drug is that it is inhibiting both mTOR and PI3K,” Dr. Layman tells SurvivorNet, adding that preclinical work also suggested suppression of Protein Kinase B, a group of enzymes inside our cells, called AKT, that manage growth, division, and survival of cells.

“So essentially the entire PAM pathway is being shut down with the molecule, and that really in theory would help reduce the risk of developing resistance.”

Dr. Layman says this is important because people who have already received CDK4/6 therapy have other treatment options available. So the real focus is whether this approach offers a useful balance between keeping the cancer under control and maintaining quality of life.

What to Know About CDK4/6 Inhibitors as Breast Cancer Treatment: Weighing the Risks vs. Benefits

3 Different Treatment Approaches

The study compared three treatment strategies after CDK4/6 therapy, including two- and three-drug combinations with gedatolisib.

Both gedatolisib approaches delayed disease progression to about 11 months, versus 5–6 months with standard treatment.

Overall, the study’s results suggest improved disease control with the drug gedatolisib.

Dr. Layman said the two-drug combo addresses a practical issue for oncologists: whether all patients need the added cost, toxicity, and complexity of another CDK4/6 inhibitor.

“There’s also the question: do you actually need the CDK4/6 inhibitor?” she said. “It’s another drug that adds cost, that adds toxicity, that adds complexity for patients.”

If the two-drug results continue to show success, the study could give doctors more options when choosing treatment. If confirmed, the results suggest doctors may choose a stronger three-drug approach for maximum control, or a simpler two-drug option for patients who need better tolerability or a less intensive treatment plan.

Dr. Layman framed that flexibility as part of the appeal of the study, saying, “I think it’s really nice to have this data, and it does give physicians and patients a choice whether they would want to do a triplet therapy or a doublet therapy based on patient preference, patients’ other medical problems and side effects that they may have had in the past.”

A key consideration is side effects, especially high blood sugar (hyperglycemia), which may strongly influence how useful gedatolisib is in practice.

If confirmed to cause fewer blood sugar issues, it could be an option for patients with diabetes or higher metabolic risk who may not tolerate other PI3K pathway drugs well.

“One major problem with these drugs is that, by their very nature of inhibiting this pathway, you get a lot of side effects,” she said. “The pathway is important in normal cells as well, not just cancer cells.”

Gedatolisib is administered by IV rather than as an oral pill, which can be less convenient since it requires scheduled clinic visits and more coordination. However, that inconvenience may be outweighed if the treatment is more effective and better tolerated.

Some patients find IV therapy harder to manage, however, others—especially those who had difficulty with oral treatments—may still prefer it if it leads to better results and improved how they feel, Dr. Layman acknowledged.

What Does This Mean For Patients?

The VIKTORIA-1 trial suggests gedatolisib may expand treatment options after CDK4/6 therapy, especially for patients who can’t tolerate existing drugs due to issues like diabetes or high blood sugar risk.

It may offer a new targeted option with a different safety profile, but it is not yet approved and still needs regulatory review.

If this drug is approved in this setting, doctors could choose between treatment combinations based on patient health, side effects, and lifestyle factors like IV vs oral therapy.

“There are patients that may be eligible to take [gedatolisib] who aren’t eligible to take some of the other PAM pathway inhibitors because of diabetes,” Dr. Layman says.

“The fact that this shows less toxicity with hyperglycemia suggests that this will open up options for patients where they really didn’t have an option to target this pathway in the past.”

Contributing: SurvivorNet Staff

Learn more about SurvivorNet's rigorous medical review process.

---