The anti-cancer drug abemaciclib (also known as Vernezio) has this month been added to the Australian Pharmaceutical Benefits Scheme (PBS) to treat certain types of breast cancer.

This significantly reduces the cost of the drug. A patient can now expect to pay A$31.60 for a 28-day supply ($7.70 with a health care concession card). The price of abemaciclib without government subsidy is $4,250.

So what is abemaciclib, and how did we get to this point?

It stops cells dividing

Researchers at the pharmaceutical company Eli Lilly developed abemaciclib and published the first study on the drug (then known as LY2835219) in 2014.

Abemaciclib is a type of drug known as a “cyclin-dependent kinase inhibitor”. It’s taken as a pill twice a day.

To maintain our health, many of the cells in our bodies need to grow and divide to produce new cells. Cancers develop when cells grow and divide out of control. Therefore, stopping cells from dividing into new cells is one way that cancer can be fought.

When cells divide, they have to make a copy of their DNA to pass onto the new cell. “Cyclin-dependent kinases” (CDKs for short) are essential for this process. So, if you stop the CDKs, you stop the DNA copying, you stop cells dividing, and you fight the cancer.

However, there are different types of CDKs, and not all cancers need them all to grow. Abemaciclib specifically targets CDK4 and CDK6. Thankfully, a lot of cancers do need these CDKs, including some breast cancers.

But abemaciclib will only be effective against cancers that rely on CDK4 and CDK6 for continued growth. This specificity also means abemaciclib is fairly unique, so it can’t easily be replaced with a different drug.

Two other CDK4/6 inhibitors were developed around the same time as abemaciclib, and are called ribociclib and palbociclib. Both of these drugs are also on the PBS for specific types of breast cancer. As the drugs differ in their chemical structures, they have slight differences in the way they are taken up and processed by the body. The preferred drug given to a breast cancer patient will depend on their unique circumstances.

What are the side effects?

Research is still ongoing into the differences between each of these CDK4/6 inhibitors, but it is known that the side effects are largely similar, but can differ in severity.

The most common side effects of abemaciclib are fatigue, diarrhoea and neutropenia (reduced white blood cells). The gastrointestinal issues are generally more severe with abemaciclib.

If these side effects are too severe, abemaciclib treatment can be stopped.

What types of cancer has abemaciclib been approved for?

In 2017, the United States Food and Drug Administration (FDA) approved abemaciclib for the treatment of patients with metastatic HR+/HER2- (hormone receptor-positive and human epidermal growth factor receptor 2-negative) breast cancer who did not respond to standard endocrine therapy.

Australia’s Therapeutic Goods Administration (TGA) similarly approved abemaciclib in 2022 as an “adjuvant” therapy (after the initial surgery to remove the tumour) for patients with HR+/HER2- invasive early breast cancer which had spread to lymph nodes and was at high risk of returning.

As of May 1 2024, the PBS covers this use of abemaciclib in combination with endocrine therapy such as fulvestrant, which is also listed on the PBS. Endocrine therapy, also known as hormonal therapy, blocks hormone receptor positive (HR+) cancers from receiving the hormones they need to survive.

Could abemaciclib be used for other cancers in the future?

Abemaciclib is of great interest to scientists and medical practitioners, and testing is ongoing to assess the effectiveness of abemaciclib in treating a range of other cancers, including gastrointestinal cancers and blood cancers.

Abemaciclib may even be usable in brain cancers, as it has long been known to be capable of crossing the blood-brain barrier, a common stumbling block for potential anti-cancer drugs.

Time will tell whether the role of abemaciclib in health care will be expanded. But for now, its inclusion on the PBS is sure to bring some relief to breast cancer patients nationwide.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute and John (Eddie) La Marca, Senior Resarch Officer, Walter and Eliza Hall Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.

However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.

While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.

The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.

Immunotherapy before surgery

Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.

Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.

Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.

This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.

Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.

The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.

Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.

Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.

Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.

The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.

mRNA vaccines

Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).

While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.

mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).

However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.

The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.

It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.

Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.

It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.

Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)

This article is republished from The Conversation under a Creative Commons license. Read the original article.