Enhertu For Advanced Her2-Positive Cancers
- FDA has approved the drug Enhertu for a huge range of advanced cancers that express the molecular factor, HER2-positive cancers.
- Doctors tell SurvivorNet this is a breakthrough, because many more people with hard to treat cancers will have another treatment option.
- Previously approved for breast, gastric cancer, and cancer in the lower end of the esophagus, Enhertu can now be offered for lung cancer, gynecological cancers, biliary tract cancers, and any type of cancer which is HER2-positive
- Patients are now advised to ask their doctor about HER2 testing and whether this new approval might give them another option. Doctors also stress that asking for data to back up this treatment decision is crucial.
- A drug approval across tumor types has rarely, if ever happened before.
“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, tells 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.”
Read MoreUnderstanding 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.
Dr. Nehra explains why: “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 adds 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,” she explains.
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.
Her2-Positive testing
Dr. Nehra says that your doctor may ask you to undergo another biopsy, which involves taking a small piece of the tumor for a lab to examine.
“We can analyze what the tumor is doing now in terms of acquiring new mutations and the landscape of its targets or traditional targets that may be useful,” she says, adding that results often come back within 48 hours so treatment decisions can be made quickly.
Your doctor will order one or more tests to understand your HER2 status, starting with an Immunohistochemistry (IHC) to measure the level of HER2 proteins on the surface of cancer cells.
IHC test scores for HER2 status in cancer diagnostics range from 0 to 3+, indicating the amount of HER2 protein overexpression on the surface of cancer cells.
- 0: No HER2 protein overexpression is detected. The cancer is considered HER2-negative.
- 1+ (Score of 1): A small amount of HER2 protein is present, but it’s still considered HER2-negative.
- 2+ (Score of 2): There’s an intermediate level of HER2 protein. This score is borderline, and further testing, usually with FISH, is recommended to clarify HER2 status.
- 3+ (Score of 3): There’s a high level of HER2 protein overexpression, and the cancer is considered HER2-positive. This indicates that the cancer may respond to HER2-targeted therapies.
Dr. Gerber says she would recommend Enhertu for any patient with an IHC score of 2+ or higher.
“If they don’t express HER2, then I would not treat them with this medication at this time with the data that we have,” she clarifies.
But, she adds, she might order further testing to better understand the nature of the tumor.
Additional tests might include:
- Fluorescence in situ hybridization (FISH) to identify the number of HER2 genes in cancer cells, indicating overexpression.
- Silver in situ hybridization (SISH) is similar to FISH, in that it detects HER2 gene amplification using a different visualization technique.
- HER2/neu testing is a broad term for tests that evaluate the presence of HER2 protein overexpression or HER2 gene amplification in cancer cells.
Related: ENHERTU Therapy Is A ‘Big Game Changer’ for HER2 Positive Metastatic Breast Cancer Patients
How Enhertu Works
Enhertu is an antibody-drug conjugate (ADC), a type of targeted cancer therapy designed to deliver cancer-killing medication directly to cancer cells. This drug consists of an antibody linked to a potent chemotherapy agent. The antibody part of Enhertu specifically recognizes and binds to HER2, a protein found in high amounts on some cancer cells.
The drug is considered ‘tumor-agnostic’ meaning its use isn’t restricted to one type of cancer. Instead, it targets any tumor that expresses the HER2 protein, regardless of the cancer’s original location or type. This broad potential makes it a versatile option in cancer treatment, particularly for patients whose cancers have a specific molecular target like HER2. Studies show that it is particularly beneficial in endometrial and other gynecological cancers.
Once Enhertu attaches to the HER2 protein on the surface of a cancer cell, it is absorbed into the cell. Inside, the link between the antibody and the chemotherapy drug is broken, releasing the chemotherapy to kill the cancer cell. This targeted approach helps to minimize the impact of the chemotherapy on healthy cells, reducing side effects and focusing the treatment’s power directly on the cancer cells.
“It’s actually a type of chemotherapy because the antibody is bringing the drug directly to the cancer cell, that drug can be dumped in directly to the cancer cell and hopefully avoid a lot of the systemic kinds of symptoms that people have as a result of chemotherapy,” explains Dr. B.J. Rimel, a gynecologic oncologist at Cedar-Sinai Medical Center in Los Angeles. “It’s not only an efficient way of bringing drug to cancer cell, but it’s also a very effective way. And recently trastuzumab oxen was approved for tumors that express this molecule, HER two, which is present in a proportion of endometrial cancers, not all of them. So a test has to be performed on a biopsy of the tumor to know if that protein is present and if the drug would be effective.”
Dr. Rimel points out that testing for this drug is simple to perform and widely available.
“Most pathology departments where patients have their tumors stored after surgery or after biopsy can perform this test, and any patient can ask for this test of their doctor and their doctor can submit a request,” she says. “It’s a very commonly done test because it was actually developed in breast cancer, and so it’s available almost everywhere. ”
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.
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,” says 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 .
Related: FDA Approves Targeted Drug ELAHERE for Certain Patients With Difficult-to-Manage Disease
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
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 says 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 says.
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.
Watch: Dr. Whitfield Growdon Explains how Elahere Works
Discussing Enhertu with Your Doctor
If you’re dealing with an advanced HER2-positive cancer and have already undergone other treatments with little benefit, talking to your doctor about Enhertu could be a valuable next step.
Key points to discuss include:
- Can I be tested for HER2-positive cancer?
- How does this treatment differ from others I’ve tried?
- What benefits can I expect?
- What are the potential side effects?
- Is the cost of this drug covered by insurance?
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