Gedatolisib Approval Offers Hope for Many With Advanced HR+ Breast Cancer, But Means More Time in the Clinic for Patients

The fact that gedatolisib is approved specifically for people whose tumors do not carry a PIK3CA mutation is important.

“Some tumors have mutations in their DNA, such as PIK3CA, for which targeted drugs have become available in recent years,” Dr. Anne O’Dea, Breast Medical Oncologist at The University of Kansas Cancer Center, tells SurvivorNet.

“PIK3CA is a part of a larger cellular signaling pathway within cancer cells that allows these cells to grow and divide. Existing drugs that inhibit PIK3CA target only a single component of the pathway, creating an opportunity for cancer cells to become resistant to that treatment and stop it from working effectively,” Dr. O’Dea adds.

“Gedatolisib is the first FDA-approved therapy that inhibits this pathway more broadly, which we believe can help overcome resistance, thus allowing the medicine to work more effectively and for a longer time.”

Cancers get sorted by their genetic quirks, and targeted drugs are usually matched to a specific flaw; the drug goes to that weak spot and attacks it there. Several of the targeted therapies aimed at this same cellular pathway were built for tumors that do carry the PIK3CA mutation, making them unavailable to a large portion of patients whose tumors don’t carry the mutation.

WATCH: Understanding Gene Mutations in Your Metastatic Breast Cancer Diagnosis Is Crucial to Your Treatment

“[Gedatolisib] is for patients who don’t have a mutation. It’s an exciting approval that’s approved either as a doublet with Faslodex (fulvestrant) or a triplet with Faslodex and palbociclib, and I think we’re very excited about it,” Dr. Eleonora Teplinsky, head of Breast Medical Oncology at Valley Health System, tells SurvivorNet.

Moving forward, cancer doctors can now test patients with HR+, HER2- metastatic breast cancer for mutations such as PIK3CA to determine if they’re eligible for this treatment path.

“For those who don’t have the mutation, we will now consider gedatolisib in combination with endocrine therapy with or without another targeted pill, palbociclib, as a potentially effective treatment option,” Dr. O’dea says.

The Data Behind Gedatolisib’s Approval

The approval rests on a trial called VIKTORIA-1. Researchers enrolled 392 people and divided them into three groups:

• One took gedatolisib plus fulvestrant plus palbociclib
• One took gedatolisib plus fulvestrant
• One took fulvestrant by itself

What they were tracking is something doctors call progression-free survival, which means how long the cancer stayed quiet before it began to grow again.

For the group on fulvestrant alone, that number was two months before the disease started advancing.

The gedatolisib groups did considerably better:

• With all three drugs together, the cancer was held in check for a median of 9.3 months
• With gedatolisib and fulvestrant, the median was 7.4 months

Tumors also shrank far more often when gedatolisib was in the mix, in roughly a third of patients on the three-drug combination, versus almost no one taking fulvestrant alone. When responses happened, they tended to last well over a year.

However, it’s not yet clear if gedatolisib actually helps patients live longer.

When the FDA reviewed the trial, the survival data weren’t mature enough to say that. Essentially, not enough time had passed.

Delaying the cancer’s growth is meaningful on its own, and it’s what the approval is built on, but a longer life is a separate question, and the answer isn’t in yet.

Gedatolisib: Side Effects

Every cancer drug asks something of the body, and gedatolisib’s most common toll is on the mouth.

Stomatitis, which refers to sores and inflammation across the lining of the mouth, showed up frequently in the trial.

It can make eating, drinking, and talking miserable for a stretch. Doctors have ways to blunt it, including medicated mouth rinses started early, and it’s worth raising with your care team before the first dose, not after the sores arrive.

The label also flags high blood sugar, skin reactions, and a serious warning for anyone who is or could become pregnant, because the drug can harm a developing fetus. As with most drugs in this class, serious complications are possible and, in rare cases, can be life-threatening, so the treatment is given under close watch.

Understanding the Tradeoffs

One practical detail to understand about gedatolisib is that it is not a pill.

Gedatolisib is administered:

• As an infusion (IV) given in the vein over the source of about a half hour
• Given once a week for three weeks out of every four

That means regular trips to an infusion center and more contact with the medical system than a daily pill.

Dr. Teplinsky says this notable difference is worth a hefty conversation while weighing treatments.

“This is a second-line therapy, and most of our patients at this point are working and living and going around doing their thing, and it’s an IV infusion, whereas before we had oral medication,” Dr. Teplinsky explains.

“Now all of a sudden, we’re going to be adding a lot of time that patients are going to be in the infusion center seeing us, getting labs, managing side effects, getting their infusion. So, I think for a lot of us, we’re excited, but that’s something that is going to be a factor that we have to talk to our patients about,” she adds.

Still, for patients who don’t carry a mutation that makes them eligible for targeted drugs, this approval adds a hopeful addition to their potential treatment options. It also highlights how important it is to test tumors and understand their genetic makeup.

Knowing the genomic makeup of a patient’s cancer “allows us to personalize their treatment plan for their specific cancer, balancing the treatment with impact on quality of life and their personal goals and values, which is essential,” Dr. O’Dea says.

Questions To Ask Your Doctor

• Has my tumor been tested for PIK3CA and other mutations?
• Should I consider adding gedatolisib to my treatment plan?
• What side effects should I be aware of?
• Are there other options I should consider before gedatolisib?

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