Lapatinib and Herceptin as a Cancer Cure: The Studies

11.19.2019 0 comments

Author: Trisha Houghton, CNS, ASIST
Medically reviewed by: Tricia Pingel, NMD

Since the dawn of time, physicians and healers have been searching for a cure for cancer. Bone cancer has been discovered in mummies dating back to 1600 BC, and the word “cancer” appears in the writings of the Greek physician Hippocrates. In modern times, pharmaceutical companies have invested billions of dollars into finding ways to cure cancer.

To date, treatments like chemotherapy, radiation, and surgical removal have proven the most common and effective options for getting rid of tumors. However, as one clinical trial in 2016 discovered, there may be a potential new solution for curing cancer—specifically, breast cancers.

That solution: a combination of lapatinib and Herceptin.

Don’t know what those are? Don’t worry, we’re about to do a deep dive into both!

In this post, we’ll take a brief look at the history of cancer cures and what options are currently available, before moving on to the results of the fascinating study conducted in the UK that showed the benefits of using these two targeted treatments.

We’ll examine what type of breast cancer this combination therapy is best suited for, what possible side effects are, and wrap up with a final look at what the future may hold for the treatment of human breast cancer.

The Search for a Cancer Cure: A Brief History

Cancer research has been ongoing for millennia, with scientists and doctors attempting to identify, diagnose, and treat it. However, the greatest strides of progress have come in the last 250 years.

According to one report from the National Cancer Institute titled “Milestones in Cancer Research and Discovery” [1], here are some of the biggest occurrences in this field of medicine:

• 1775: Percival Pott identifies a connection between squamous cell carcinoma of the scrotum and exposure to chimney soot among chimney sweeps. This is the first report to link environmental exposures to cancer development.
• 1863: Rudolph Virchow connects inflammation and cancer by identifying white blood cells in cancerous tissues. Excess white blood cells are recognized as a form of cancer and called “leukemia”.
• 1886: Hilário de Gouvêa provides the first evidence that cancer can be inherited, reporting that two of the seven children born to a father suffering from malignant eye tumors (retinoblastoma) also developed the same tumors.
• 1899: Tor Stenbeck and Tage Sjogren, two Swedish physicians, use X-ray therapy to treat and cure squamous cell carcinoma and basal cell carcinoma of the skin.
• 1911: Peyton Rous identifies a virus that causes cancer to develop in chickens, thereby proving that some cancers can be caused by infectious agents.
• 1928: George Papanicolaou discovers that examining vaginal cells under a microscope can help identify cancer cells. This ultimately leads to the development of the pap smear.
• 1937: Sir Geoffrey Keynes publishes a paper describing a breast cancer treatment that involves first surgery to remove the tumor, then long needles inserted to inject radium directly to the affected breast tissue and nearby lymph nodes. This is the first non-mastectomy procedure documented for treating breast cancer.
• 1941: Charles Huggins discovers that hormone therapy (in this case, lowering testosterone production by removing the testicles) causes the regression of hormone-dependent tumors—in this case, prostate tumors.
• 1950: Cigarette smoking is identified as a major contributing factor to the development of lung cancer.
• 1953: Roy Hertz and Min Chiu Li are the first to completely cure a solid tumor in humans using chemotherapy (methotrexate).
• 1958: Emil Frei, Emil Freireich, and James Holland and other researchers from the NCI prove that combination chemotherapy (using 6-mercaptopurine and methotrexate) can induce partial and/or complete remissions and extend the lifespan of patients suffering from acute leukemia.
• 1964: The Epistein-Barr virus is linked to Burkitt lymphoma, later leading researchers to connect the EBV virus to other cancers, including gastric cancers, Hodgkin lymphoma, and nasopharyngeal carcinoma.
• 1984: Researchers discover the HER2 gene, and identify that its overexpression can lead to not only the formation of 20 to 25% of breast cancers, but also create a more aggressive form of cancer with a poorer prognosis.
• 1996-2009: Medications like anastrozole, rituximab, trastuzumab, imatinib mesylate, Cerverix, and Gardrasil are introduced and approved to treat tumors and reduce cancer risk, particularly hormone-resistant prostate and breast cancers.
• 2014: Researchers from the National Cancer Institute and the National Human Genome Research Institute find from DNA analyses that stomach cancer is, in fact, four different conditions, and create a new classification system for cancers.
• 2017: The FDA approves two genomic profiling tests to test tumors for genetic changes that could make them more susceptible to molecularly targeted drug treatments.
• 2019: The NCI launches the Childhood Cancer Data Initiative (CCDI) to gather information to be shared and analyzed with the end-goal of addressing cancer in children, teenagers, and even young adults.
• 2020: The FDA approves the first blood tests that scan DNA shed into the bloodstream by tumors to identify any cancer-related genetic changes. These tests, called “liquid biopsies”, can be used to not only assess the DNA characteristics of tumors and cancer cells, but also identify if drug treatments are working.
• 2023: The National Institutes of Health release a comprehensive dataset containing clinical, imaging, proteomic, and genomic data for more than 1,000 tumors across 10 different types of cancer.

As you can see, the identification and treatment of cancers have come a long way over the last 250 years!

A Groundbreaking Study: Lapatinib and Herceptin’s Potential to Cure Cancer

At the beginning of this post, we mentioned a 2016 study that involved lapatinib and Herceptin, combining the two therapies into one to address breast cancer.

We will share with you all the data below, but before we do, there are a few things you need to understand.

First, what are lapatinib and Herceptin?

Both drugs are individually used to treat breast cancer, specifically HER2 positive breast cancer.

Lapatinib blocks the HER2 proteins inside breast cancer cells. It’s a kinase inhibitor that interferes with HER2-related kinases that give the cancer cells the ability to grow and multiply.

Herceptin, on the other hand, blocks HER2 proteins on the surface of breast cancer cells. It attaches to the HER2 receptors on cancer cells and stops them from receiving signals to multiply and grow. It can also alert the immune system to treat the cancer cells as hostile and eradicate them.

Understanding HER2-Positive Breast Cancer and the Study’s Focus

The study focused on HER2-Positive Breast Cancer, a subtype of breast cancer that (as you may recall from the information above) is highly aggressive and invasive. It contributes to the formation of around 1 in every 5 breast cancers.

HER2-Positive breast cancer is marked by high levels of a protein called “human epidermal growth factor receptor 2”, which controls how your cells divide and grow. When present in high levels, this protein can cause cells to divide and grow out of control, leading to higher rates of cancer formation as well as greater risk of metastasis.

The 2016 study [2] focused specifically on treating this type of breast cancer, using two drugs that have been previously used on their own. As you’ll see by the data below, the combination therapy led to a statistically significant difference!

The 11-Day Treatment: Results of Lapatinib and Herceptin on Breast Cancer

Scientists funded by Cancer Research UK found that a pair of drugs–Lapatinib and Herceptin (generic name: trastuzumab)—were able to eliminate breast cancer in just 11 days, without the need for chemotherapy or surgery.

The study involved women with HER2 positive breast cancers. 257 female breast cancer patients participated in the study, and 130 of patients treated were assigned at random to one of three groups:

• Control group – This group received no initial treatment before undergoing surgery 11 days after the study’s onset.

• Herceptin group – This group received the trastuzumab based therapy for 11 days before undergoing surgery.

• Lapatinib group – This group received the Lapatinib treatment for 11 days before undergoing surgery.

The results of the 11-day treatment period were remarkable! The women who received a combination of these two drugs were more likely to show visible results. 7 of the 66 women treated with the drugs had NO cancer cells remaining after two weeks of medication. 11 more women showed dramatic shrinkage in their tumor sizes.

The Meta-Analysis: Combining Lapatinib and Herceptin for HER2-Positive Cancer (existent)

In a 2017 meta-analysis[3], the results of 7 randomized controlled trials including more than 2000 women were reviewed to determine the effectiveness of the combination of these two drugs (Herceptin and Lapatinib).

According to the study, “the combination of lapatinib and trastuzumab significantly improved pathological complete response, event-free survival, overall survival, and toxicities in the treatment of HER2-positive breast cancer compared with trastuzumab or lapatinib alone.”

What’s cool about the combination of drugs is that the size and hormone receptor status of the tumors didn’t affect the outcome. Even if the solid tumors were larger, they were visibly affected (shrunk) by the combination of these two medications.

The Side Effects of Lapatinib and Herceptin: Weighing the Risks

Now, it’s important to know that there are downsides to the drug combination. According to the meta-analysis, “more frequent grade 3 or 4 adverse events…were found in the combination group than in the trastuzumab or lapatinib group.”

These “adverse events” include:

• Diarrhoea
• Rash or erythema
• Neutropenia
• Hepatic adverse events

Pairing the two medications can have more visible negative effects than simply using them alone.

But compare that to the kind of effects you’d get while undergoing chemotherapy or radiation treatment:

• Fatigue
• Hair loss
• Infection
• Anemia
• Nausea
• Vomiting
• Easy bleeding and bruising
• and the list goes on!

The side effects of this drug combination are far less debilitating or weakening than the sort of side effects common to the stronger, more invasive forms of cancer treatment.

The Promise of Lapatinib and Herceptin: A New Approach to Cancer Treatment

Could this be the first step toward a new way of fighting cancer?

There is still a lot of research yet to be done. Scientists need to dig deeper through further clinical trials to find out if these drugs can not only kill off existing tumor cells, but also prevent invasive breast cancer recurrence.

However, the good news is that this discovery could lead researchers in a new direction to deal with cancers without the need for invasive surgeries, harsh radiation, or potent chemotherapy drug cocktails. This could be a huge step forward in the war on one of the deadliest, most terrifying diseases in the world today!

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Frequently Asked Questions

How do HER2 inhibitors work?

Both lapatinib and Herceptin are HER2 inhibitors, meaning they interrupt the pathways by which the HER2 proteins promote the abnormal cell growth—which ultimately leads to the growth of cancer cells. Some HER2 inhibitors block the HER2 protein on the cell surface, while others target the protein already present inside the cell. There are also HER2 inhibitors that stop the cell from receiving signals to grow or trigger an immune response so the body naturally eradicates the cancerous cells on its own.

Is Herceptin chemotherapy or immunotherapy?

Herceptin is a form of immunotherapy that targets the HER2 receptors on cancer cells. It is often used alongside chemotherapy drugs (to great effect), but is not a chemotherapy treatment. It simply helps your immune system identify cancer cells (specifically, the HER2 receptors on the cancer cells) for destruction by your own immune cells.

What to avoid while on Herceptin?

Drinking alcohol and smoking while on Herceptin can be an increased risk to cardiac safety, potentially damaging to your heart, as well as reduce the effectiveness of the treatment. Certain herbal supplements—like St. John’s Wort, ginseng, milk thistle, and black cohosh—can negatively interact with Herceptin and affect how the immunotherapy drug is processed by your body. Given that you’re taking Herceptin to treat cancer, you should also avoid any cancer-causing foods, including high-sugar foods, processed and artificial foods, and foods high in trans and saturated fats.

Resources

HER2-positive breast cancer: What is it?

HER2-Positive Breast Cancer

Combination of lapatinib and trastuzumab shrinks HER2 positive breast cancer significantly in 11 days after diagnosis

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