Experimental Drug Gedatolisib Shows Promise For Patients With Advanced Breast Cancer After Treatment Stops Working

The trial looked at adding gedatolisib, an experimental cancer drug [that blocks signals tumors use to grow and survive] given through an IV, combined with fulvestrant (brand name: Faslodex), a prescription hormone therapy, with or without the CDK4/6 inhibitor palbociclib (an FDA-approved targeted therapy known by it’s brand name: Ibrance) to address this need.

Dr. Rachel Layman, a professor of breast medical oncology at MD Anderson Cancer Center and a co-author of the VIKTORIA-1 study, tells SurvivorNet the drug is designed to hit a pathway involved in cancer development that has long been difficult to treat.

“What is different about this drug is that it is inhibiting both mTOR and PIK3CA,” Dr. Layman says. PIK3CA is a common gene mutation and mTOR is a gene that helps make a protein that controls how cells grow and survive, however when it becomes overactive it assist cancer cells to grow faster.

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

RELATED: For Advanced Breast Cancer With a PIK3CA Mutation, A New Three-Drug Combination Doubles Progression-Free Survival, According to New Study

Promising Trial Results

VIKTORIA-1 is a phase 3, randomized, open-label trial. It enrolled adults with HR+, HER2- advanced breast cancer whose disease had progressed during or after prior treatment with a CDK4/6 inhibitor and an aromatase inhibitor. Aromatase inhibitors are drugs that lower estrogen by blocking the enzyme that makes it. This can slow the growth of cancers that depend on estrogen.

Hormone Therapies for Breast Cancer: Aromatase Inhibitor

The trial separated patients by whether their tumors had a PIK3CA mutation. That matters because this mutation can help drive cancer growth and may influence which targeted therapies are most appropriate.

For patients with PIK3CA-mutant disease, the trial compared gedatolisib plus fulvestrant and palbociclib, or gedatolisib plus fulvestrant, against alpelisib (a pill that blocks the PI3K pathway to help slow cancer growth and known by the brand name: Piqray) plus fulvestrant, an existing targeted treatment option for some patients with this mutation.

The results were promising:

• In the PIK3CA-mutant group, the gedatolisib triplet delayed cancer growth longer than alpelisib plus fulvestrant.
• Median progression-free survival, or the time patients lived without their cancer growing or spreading, was 11.1 months with the gedatolisib triplet compared with 5.6 months with alpelisib plus fulvestrant.
• The gedatolisib doublet also showed median progression-free survival of 11.3 months.

Overall survival data were still immature at the time of reporting, meaning longer follow-up is needed.

The findings support that idea that targeting more of this pathway, known as PAM, could be beneficial, Dr. Layman says.

“What we saw was that not only was it as good as alpelisib, it was much, much better,” she explains. “So that does show that the efficacy is promising with when you shut down the entire pathway.”

Risks & Side Effects of Gedatolisib

One practical issue for patients is that gedatolisib is given intravenously. That means spending more time at an infusion center, which can be difficult for patients who live far away or have work and family responsibilities.

Dr. Layman says that tradeoff should be discussed honestly.

“I think it’s important to discuss that because it’s IV that will require more time in the infusion area,” she explains. “But I really do feel like the benefits of the drug warrants it being IV.”

She also notes that side effects are a key part of the conversation.

PI3K-pathway drugs can cause problems such as:

• High blood sugar
• Diarrhea
• Rash
• Mouth sores

Dr. Layman adds that severe high blood sugar appeared less common with gedatolisib than with some other drugs in this class.

For patients, the main takeaway is that tumor testing and newer targeted therapies are giving doctors more information — and potentially more choices — when breast cancer changes over time.

“My message to patients is that we are in a really exciting time right now,” Dr. Layman adds.

Questions To Ask Your Doctor

• Has my tumor been tested for PIK3CA and ESR1 mutations?
• What treatment options are available if my cancer progresses after a CDK4/6 inhibitor?
• What are the possible benefits and risks of gedatolisib-based treatment?
• How often would I need to come to the infusion center for this treatment?
• Are there clinical trials I should consider now?

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