One of the drugs that have revolutionized the treatment of metastatic breast cancer has been approved, at European level, even in the early stages of the disease, to prevent relapse in patients at high risk.
Let’s talk about abemacicliban inhibitor of cyclin-dependent kinases – CDK 4/6 – which in the near future may therefore be used as an adjuvant therapy, that is, to be used after surgery, in combination with endocrine therapy.
A decision based on data from the monarchE study, in which the association has been shown to reduce the likelihood of the disease returning, especially with metastases, by 32%. For nearly two decades, experts say, there has been no substantial clinical improvement in early stage hormone-sensitive breast cancer.
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The news concerns all patients with a “hormonal” type of cancer, that is the most common (positive for hormone receptors and negative for the human epidermal growth factor receptor 2), who have the criteria of “high risk”. What is meant? In this case, with at least 4 positive lymph nodes, or one to three positive lymph nodes with grade 3 disease, or with a tumor larger than 5 centimeters.
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“In metastatic breast cancer we have had such important results that they have led us to study CDK 4/6 kinase inhibitors even at an earlier stage of the disease,” he tells Seno Health. Valentina GuarneriFull Professor of Medical Oncology and Director of the Complex Operative Unit of Oncology 2 at the Istituto Oncologico Veneto IRCCS: “The first data showing a significant reduction in the risk of relapse in these patients were presented in the autumn of 2020, in course of the annual ESMO congress. Those results were followed by others which confirmed the benefits also from a clinical point of view “.
This led to the approval of abemaciclib as the first anti-CDK 4/6 for adjuvant therapy by the US regulatory agency last October and, now, also by the European one.
The development of anti-CDK 4/6
Cyclin-dependent kinases 4 and 6 are molecules that increase the rate at which cancer cells grow and divide. The first attempts to modulate the life cycle of cells to treat cancer date back to the 1990s, but the toxicity and lack of specificity of the drugs used had led to a failure of the trials. Later, however, in vitro and animal model studies of selective CDK4 / 6 inhibitors showed promise, especially for hormonal-type breast cancer.
Three of these inhibitors – palbociclib, ribociclib and abemaciclib – rapidly progressed to phase III studies for metastatic breast cancer. The results exceeded expectations and were better than any previously reported for this stage of the disease. It was logical – and it is practice – to look at the earliest stages. To date, the studies on palbociclib as adjuvant therapy they have not been positive, while those on are still awaited ribociclib.
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“The three anti-CDK 4/6 drugs available are similar, but not entirely the same and have their own peculiar activities”, explains Guarneri: “Even the studies that have tested them as adjuvant therapy are not completely overlapping. To date they have never been direct comparative studies have been made between these three molecules, not even in the metastatic phase, so it is not possible to compare them. We are now awaiting the results of the Natalee study, which tested ribociclib as an adjuvant therapy for a period of three years. ”
Understanding the right sequences and combinations
What is certain is that the scenario is rapidly changing and new generation anti-CDK and new hormonal therapies are already being studied. Other research is investigating how to overcome resistance mechanisms to these drugs.
“For the future – continues the oncologist – we expect a drop in the percentage of relapses, while for those who develop the disease again we will have an increasingly rich plethora of therapeutic possibilities. Thanks to tools such as liquid biopsy, moreover, we will probably be able to follow the evolution of the disease also from a molecular point of view, to personalize the treatment strategy “.
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In an article published on The Asco Post, Gabriel HortobagyiProfessor of Medical Breast Cancer Oncology at MD Anderson Cancer Center (in Texas), writes that there are many reasons to be optimistic.
The median survival of patients with “hormonal” metastatic breast cancer treated with ribociclib exceeded 5 years in MONALEESA-2 – meaning that half of patients live beyond this period – and the survival of patients with stage disease initial is excellent. It is likely – the expert reports – that the new treatment options will further improve these results. The challenge now is to determine the right combinations and sequences and identify biomarkers to select the most appropriate treatment for each patient.
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“I believe it is important – concludes Guarneri – to be able to use as an adjuvant therapy a drug that has been shown to significantly reduce the risk of relapse, because it means potentially being able to avoid metastatic disease, and therefore aim at healing from breast cancer. , for an important portion of high-risk patients. We know that this drug is very effective even in the advanced phase, when however the goal is no longer healing, but disease control “.