A Promising Drug for Advanced Her2-Positive Breast Cancer
- Irish singer Linda Nolan, 65, who rose to fame with her five sisters in The Nolans band in the mid-1970s, is fighting advanced stage breast cancer, but holding on to hope and ‘ready to try anything’ after being told the cancer in her brain has spread.
- The breast cancer survivor said she will be starting the targeted drug Enhertu for her HER2-positive metastatic cancer. Breast cancer classified as HER2-positive tends to exhibit faster growth, increased likelihood of spreading (metastasis) and a higher chance of recurrence. Nolan was initially diagnosed with stage 3 cancer in 2005 and went into remission, but then the cancer returned in 2017 to her hip, then to her liver and brain.
- Enhertu, which received an accelerated approval in the United States, but has still not received approval in England and Wales, has demonstrated fewer side effects than chemotherapy and other traditional cancer treatments. But like all medications, it can cause some reactions such as nausea, fatigue and hair loss, though not everyone experiences them the same way.
Breast cancer classified as HER2-positive tends to exhibit faster growth, increased likelihood of spreading (metastasis) and a higher chance of recurrence. Nolan was initially diagnosed with stage 3 cancer in 2005 and went into remission, but then the cancer returned in 2017 to her hip, then to her liver and brain.
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Hope for All Women to Have Access to Enhertu
“To be able to try a new drug is amazing, I just wish everyone could have this opportunity,” she said, referencing how the drug has been rejected in England’s NHS healthcare system and it has been rejected in Wales. “To be able to try this is hope — it’s a plan B not everyone is being allowed. To take this drug away from women is to take away their hope.”
Nolan’s most recent scans show that two of her largest tumors in the front and left side of her brain have grown, along with a “slight increase” of growth in the smaller spots surrounding them.
“I had feared something was wrong. My balance has been getting worse and my memory — my sisters have to prompt me when I get lost in the middle of a sentence.”
Nolan, who lives with her sister Denise in the seaside town of Blackpool, Ireland, is dreading more side effects, like losing her hair. When Nolan’s consultant told her “it is a possibility,” she told him, “That will be five times I’ve lost my hair!”
“But if it happens, I’ll just shave it again,” she said a beat later with a bit more optimism. “Thankfully, he is not saying ‘we can’t do anything for you.’ We have more places to go. I am ready to try anything. I have done this before and I can do it again.”
Understanding HER2-Positive Cancers
HER2-positive refers to a characteristic found in certain cancer cells, where there’s an overexpression, or high level, of the HER2 protein.
This protein is a receptor on the surface of cells. When activated, the protein promotes cell growth.
In certain types of cancers, this overexpression leads to the cancer cells growing and dividing much faster than normal cells, leading to disease that is far more aggressive compared to cancers that don’t express high levels of HER2.
“Targeted drugs” like Enhertu directly seek out and bind to HER2 proteins to effectively slow down or stop the growth of the cancer. Because it avoids harming healthy tissue surrounding the cancer, it can have fewer side effects compared to traditional chemotherapy.
Physician-Scientist Gerold Meinhardt Explains Enhertu’s Cross Tumor ‘Rare’ Approval
“The drug was actually previously approved for breast cancer and gastric cancer and cancer in the lower end of the esophagus,” Dr. Anupama Nehra, the clinical director of hematology/oncology at the Rutgers Cancer Institute at University Hospital in New Jersey, explained in a previous interview with SurvivorNet. “Now it is approved for lung cancer, gynecological cancers, biliary tract cancers – any type of cancer which expresses a target in the cancer cells called HER2-positive.”
Continuing, Dr. Nehra said, “It’s a bioengineered drug that essentially has more of an effect on the tumor cells compared to normal cells. So use of this medication actually helps minimize some of the effects on the normal tissue, but maximize the effects on the tumor tissues.”
Dr. Nehra added that the drug delivers even more benefit thanks to a phenomenon called “the bystander effect.”
“This basically means that the surrounding tumor cells are also targeted by the medication.”
Dr. Deanna Gerber, a gynecologic oncologist at the Perlmutter Cancer Center at NYU Langone Hospital in Long Island, NY says that the benefits are especially exciting for gynecological cancers such as ovarian and cervical cancer.
Who Benefits from Enhertu?
Enhertu is right for a adult patients who have HER2-positive solid tumors for any type of cancer that are:
- Unresectable (cannot be removed by surgery)
- Metastatic (spread to other parts of the body)
Your doctor may consider Enhertu if other systemic therapies, such as chemotherapy or other HER2-targeted treatments, have been unsuccessful.
The US Food and Drug Administration (FDA) granted Enhertu an “accelerated” approval based on the early results of the DESTINY trials, a set of key studies that focused on different types of cancer and treatment scenarios involving the use of Enhertu.
Clinical Trials for Breast Cancer
The results were promising:
Enhertu reduced tumor size or disease spread in 46.9%-52.9% of patients, which is significantly higher compared to many other treatments.
In certain studies, Enhertu extended overall survival by as much as 9 months compared to other therapies. While the exact results varied depending on the trial, patients receiving Enhertu generally report fewer severe side effects compared to traditional chemotherapy.
“In clinical trials, tumors with Her2 overexpression had higher chances of responding to therapy and stabilizing the disease process,” said Dr. Maryam Lustberg, director of the center for breast cancer at Smilow Cancer Hospital and Yale Cancer Center. “The right treatment will stabilize disease process and will also have good quality of life and an acceptable side effect profile.”
In other trials, patients treated with Enhertu experienced longer periods where their cancer did not worsen — 4 to 8 additional months compared to patients receiving other treatments.
The FDA has requested further testing before it grants Enhertu full approval.
Enhertu has already been incorporated into the National Comprehensive Cancer Network (NCCN) guidelines for advanced tumors, recommendations put together by an alliance of 33 leading cancer centers in the United States.
NCCN Guidelines state that Enhertu should be the first-line treatment for previously treated patients with metastatic HER2-positive solid tumors. Additionally, it’s a preferred drug for HER2-low metastatic breast cancer and a second-line option for HER2-negative metastatic breast cancer .
Side Effects To Watch For
Enhertu has demonstrated fewer side effects than chemotherapy and other traditional cancer treatments. But like all medications, it can cause some reactions, though not everyone experiences them the same way.
Common side effects include:
- Nausea
- Fatigue
- Hair loss
- A decrease in white blood cells, which can raise the chances of infection
Dr. Gerber points to a less common but more serious side effect to watch for: lung problems.
“Some of the exposures and the actual toxicity that we’re seeing with this drug specifically is the risk of interstitial lung disease,” she says.
Interstitial lung disease refers to a group of conditions that cause scarring (fibrosis) and inflammation of the tissues surrounding the air sacs in the lungs. This scarring makes the lungs stiff and can significantly impair the ability to breathe and get oxygen into the bloodstream.
Other rare but serious side effects include heart issues, and severe allergic reactions. It’s also worth noting that Enhertu can cause harm to a fetus, so it’s not recommended for use during pregnancy.
Yet despite the possibility of side effects, Dr. Gerber says she feels the drug’s benefits outweigh the risk in patients who are eligible to receive it.
The Significance of This Approval in the U.S.
This FDA approval of Enhertu is significant for several reasons.
First, it provides a new treatment option for a challenging group of cancers, potentially improving patient outcomes and offering another line of defense against the disease.
Second, the approval is based on promising clinical trial data, showing that Enhertu can effectively slow the progression of these aggressive cancers in some patients.
For the doctors and the patients they treat, this approval represents progress in the ongoing battle against cancer. It’s not just about having another treatment available – it’s about offering a targeted therapy that can make a real difference when there are few other choices.
Dr. Gerber says that it’s especially exciting for gynecological cancers where the studies returned the best results.
“In our recurrent gynecologic cancer patients such as cervical cancer, endometrial cancer and ovarian cancer patients who have received prior therapy, we usually see pretty low response rates. But this drug showed very impressive response rates –greater than 40% for most gynecologic cancers with 2+ IHC scores or higher,” she says.
Dr. Nehra said that Enhertu moves the idea of “personalized medicine” firmly into mainstream cancer care.
“The treatments are getting more customized. They are not and not really like one size fits all anymore. This is really a breakthrough,” she expressed.
While no expert claims that it’s a cure-all, Enhertu adds a critical tool in the fight against these aggressive tumors. For patients facing limited treatment possibilities, that means real hope.
Contributing by SurvivorNet staff.
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