Enhertu for Non-Small Cell Lung Cancer
- About 2% of lung cancer patients have a mutation in the human epidermal growth factor receptor 2 (HER2), which is on the surface of almost all the cells in our body and it is responsible for the communication between cells to promote growth, division, and repair.
- An error in the HER2 gene is something that doctors can look for when deciding how to treat non-small cell lung cancer (NSCLC).
- The drug Enhertu (generic name trastuzumab deruxtecan) might be an option for HER2-mutant metastatic or non-operable NSCLC.
- Looking for an error in the HER2 gene can help doctors determine the best course of treatment for NSCLC.
- Patients are encouraged to ask their doctor about testing for mutations and if they may be eligible for a therapy like Enhertu.
Stage four is the most advanced cancer stage. Unfortunately, lung cancer is commonly already in stage four when it is first diagnosed. The National Cancer Institute estimates that about 55% of lung or bronchus cancers are first diagnosed at this stage.
Read More“This is an exciting development for our patients with a HER2 mutation as until this drug became available we did not have any standard HER2-targeted therapies available, and with the approval of this drug it is now established that biomarker testing for people with a new diagnosis of advanced lung adenocarcinoma should include testing for HER2 mutations,” Dr. Julia Rotow, Clinical Director of the Lowe Center for Thoracic Oncology, affiliated with Dana-Farber Cancer Institute, told SurvivorNet.
What Is HER2?
The human epidermal growth factor receptor 2 (HER2) is a receptor on the surface of almost all the cells in our body, and it is one of the many receptors responsible for the communication between the cells to promote their growth, division, repair, and survival.
In other words, HER2 is one of the many receptors that help cells grow and divide when the timing is right.
An error in the HER2 gene is something that doctors can look for when deciding how to treat NSCLC, as well as several other cancers. According to the American Lung Association, about 2% of lung cancer patients have a HER2 mutation.
Dr. Geoffrey Oxnard explains how genetics play a role in lung cancer treatment.
How Does Enhertu Work?
Enhertu is a targeted therapy, which means it specifically identifies and attacks certain types of cancer cells. You may hear doctors refer to it as an antibody-drug conjugate targeted therapy.
The antibody selectively binds to the HER2 proteins on the surface of lung cancer cells and infuses highly potent chemotherapy directly into those cancer cells. This selectivity allows for the sparing of normal cells and the consequent side effects.
"As Enhertu targets the protein HER2, attached to it is a toxin that hopefully will kill the cancerous cells. It's targeting a therapy in a precise way by attaching to the tumor to deliver treatment,” Dr. Roy S. Herbst, Chief of Medical Oncology at Yale Cancer Center, told SurvivorNet.
Enhertu for HER2+ Lung Cancer
Enhertu is a prescription medicine used to treat adults who have NSCLC with HER2 gene mutation and cannot be removed by surgery or has spread to other parts of your body (metastatic), and who have received a prior treatment.
It is taken alone, without the need for other medicines, to treat unresectable or metastatic NSCLC. It is given as an intravenous infusion once every three weeks.
The first infusion will take about 90 minutes so the doctor can see if there are any side effects or problems. Future infusions should take about 30 minutes, if the first infusion was well tolerated.
Who Is Eligible for Enhertu?
To be eligible for treatment with Enhertu, patients must have cancer that can't be removed by surgery (unresectable) or has spread to other parts of the body (metastatic), and they must have already received one or more cancer therapies.
"HER2 is mutated in only about 2% of patients with lung cancer, and this drug has been targeted to that small group, but data have emerged showing that it works in even a broader group of patients than were tested, and probably will benefit between 10% and 20% of patients with lung cancer, at least on the first go around,” adds Dr Herbst.
Researchers from Memorial Sloan Kettering Cancer Center published a study in The New England Journal of Medicine that highlighted the benefits of Enhertu for treating people with HER2-mutant NSCLC.
Dr. Bob Li, a Thoracic Oncologist at Memorial Sloan Kettering Cancer Center, said that the results from the study are extremely promising for this group of patients who have typically been difficult to treat with other forms of therapies.
"Researchers and physicians at MSK have been studying HER2 in lung cancer for two decades, and this marks another paradigm-shifting therapeutic breakthrough for patients,” he said.
The study confirmed that about half of the patients objectively responded to treatment, with a median duration of response of 9.3 months and a median progression-free survival of 8.2 months.
Should all lung cancer patients receive Enhertu?
“Not all patients with lung cancer should receive this treatment, but it does mean that all potentially eligible patients should receive the correct tumor testing to know if their lung cancer has a HER2 mutation,” Dr. Rotow stressed.
“Specifically, everyone with advanced or metastatic lung adenocarcinoma should have this testing on their tumor biopsy sample, typically done through a type of testing called next generation sequencing,” Rotow added.
“Some patients with the other main subtype of non-small cell lung cancer, called squamous cell carcinoma, could also consider being tested. This is particularly important for younger patients and those without a history of tobacco use, for whom the chances are higher of finding a mutation like HER2 which may impact treatment options. HER2 is only one of multiple different gene alterations in lung cancer that have personalized therapies associated with them and an advantage of next-generation sequencing is that it includes all of these genes not just HER2.”
Dr. Herbst reinforces that only patients that have evidence of a HER2 abnormality should receive Enhertu, but he adds, “Research is ongoing, including here at Yale, to try to expand the impact to an even larger group. The DESTINY study is looking at this with broader groups of patients, with lower amounts of HER2 protein on their cell surface."
Lung Cancer: The Basics
Lung cancer ranks as the second-most prevalent cancer and is the leading cause of cancer-related deaths among both men and women in the United States. Treating this disease can be particularly challenging since symptoms often remain undetectable until the cancer has already spread to other organs.
Doctors categorize lung cancer into two primary types based on their behavior and treatment approach:
- Non-small cell lung cancer (NSCLC): This is the more frequent type, accounting for approximately 85% of cases. NSCLC grows at a slower pace compared to other types and is treated differently.
- Small cell lung cancer (SCLC): Although less common, SCLC tends to exhibit rapid growth when compared to NSCLC. Consequently, it requires a distinct treatment approach.
Dr. Joseph Friedberg explains how lung cancer is diagnosed.
Potential Side Effects of Targeted Therapy
The negative effects of targeted therapy can be quite severe, so it's important to inform your physician as soon as you experience any abnormal symptoms. Those who are taking more than one immunotherapy drug, referred to as combination therapy, are at an increased risk of experiencing side effects.
Common immunotherapy side effects include:
- Nausea/vomiting
- Decreased white blood cell count
- Anemia: decreased hemoglobin
- Fatigue
- Constipation
- Decreased appetite
There were several other potential side effects listed as well. Before beginning any new treatment, it's important to discuss potential side effects with your doctor or medical team.
To help manage the side effects, the healthcare provider may:
- Reduce the dose
- Delay the dose
- Or even stop the medication.
Clinical Trials
Clinical trials are incredibly important both from an individual and a societal standpoint. These studies give patients, who have diseases that are not responding to typical treatments, access to a bevy of new drugs that are currently being developed by pharmaceutical companies.
Testing these treatments on people in experimental trials is really the best way for research to progress.
A lot of the therapies being tested in clinical trials will fail. However, participants in clinical trials are statistically more likely to have better outcomes, according to the Director of NYU Perlmutter Cancer Center, Dr. Ben Neel.
Among the large group of clinical trials that are currently underway, there will be some dramatic successes.
Dr. Ben Neel explains why he’d choose a clinical trial for himself.
NCCN guidelines include Kadcyla (generic name ado-trastuzumab emtansine) as another option outside of Enhertu, for patients with advanced NSCLC who have progression after prior therapy. However, as of today, Kadcyla is only FDA-approved for the treatment of breast cancer. Some patients could be eligible to receive it if they were enrolled in a clinical trial.
SuvivorNet has a Clinical Trial Finder specifically designed to help patients navigate their options. You may see new results over the course of several days as new clinical trials are added daily.
You can also use clinicaltrials.gov, which is the national registry of trials, but it's vast and a bit hard to navigate.
Consider asking:
- Is there any clinical trial on advanced non small-cell lung cancer?
- Am I eligible for a clinical trial?
Questions to Ask Your Doctor
If you have advanced non small-cell lung cancer, it’s important you ask your doctor about testing for mutations and what treatments you may be eligible for. Here are some questions you may consider asking to get the conversation started:
- What tests are available to determine if my cancer has mutations?
- What is my HER2 status & am I eligible to be treated with Enhertu?
- What will the treatment plan look like?
- What are the most common side effects of Enhertu? Are there other risks?
- Are there ways to help manage those side effects?
- How can we weigh the risks vs. benefits of this new drug?
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