Bengaluru: In a phase three trial involving 557 advanced breast cancer patients, an experimental treatment with a known drug has resulted in metastatic or invasively spreading cancer to not grow at all for 10 months — results unheard of previously in metastatic breast cancer trials.
The trail was randomised, and patients who took the drug, trastuzumab deruxtecan, found that their tumours stopped growing for at least 10 months, whereas in standard chemotherapy the growth stopped for five months, on average.
The patients all had low levels of human epidermal growth factor receptor 2 (HER2) protein, which aids the growth of cancer cells. It is a normal protein found in breast cells, but one in every five cases of breast cancer sees individuals producing very high levels of the protein, which make the cancer very aggressive.
HER2-inhibiting drugs have been successful in treating breast cancer in patients with high levels of HER2 protein, but those who do not produce high enough levels are still under risk and do not respond as well to previously tested similar treatments.
The study showed that not only did tumours not grow in HER2-low patients, but those who had taken the experimental drug survived for two full years, as compared to those who received standard chemotherapy and survived an average of 16 months.
The study was conducted at the Memorial Sloan Kettering Cancer Center in New York, and was sponsored by the pharmaceutical companies Daiichi Sankyo and AstraZeneca, which have jointly developed the drug.
The findings were presented to a standing ovation in an oncology conference Sunday, and have been published in the journal, the New England Journal of Medicine.
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How the drug works
The drug is sold under the brand name Enhertu and belongs to a new class of drugs called antibody conjugates (ADCs).
ADCs are targeted therapies for treating cancer, as compared to generic chemotherapy drugs that also destroy healthy cells. These drugs use the targeting abilities of monoclonal antibodies and carry with them cancer-killing drugs, the combination of which can recognise healthy cells from cancerous cells.
It is comprised of trastuzumab — a humanised monoclonal antibody, which is bound to the topoisomerase inhibitor, deruxtecan. Topomerase inhibitors are those that prevent cells from making structural changes to DNA and replicate, destroying it when it attempts to replicate.
The trastuzumab molecules bind to the HER2 receptors in the body, preventing replication. They are then absorbed into cells as well. Deruxtecan is the chemotherapy molecule in this drug which acts once inside the cells.
The drug is already approved for HER2-positive breast cancer patients, or those with high levels of the protein, as it targets cells that are filled with the protein, which breast cancer cells are, if positive. The drug is not used for HER2-low patients because other similar drugs have failed to treat such cancers.
However, the authors found that the drug enters any cell with HER2 protein on its surface, meaning that the drug will enter HER2-low patients’ cells as well, moving through cell membranes and in between cancer cells.
The drug also produced expected chemotherapy side effects of nausea and vomiting, with three patients dying due to lung injuries. The authors note that serious adverse events occurred in over 52 per cent of the patients who received the drug, and in 67 per cent of those undergoing standard chemotherapy. Twelve per cent of the volunteers receiving the drug developed drug-related lung disease.
Trastuzumab deruxtecan is used in advanced stages of breast cancer and is not suitable for early stage just yet, until trials are completed. The findings provide an effective alternative to standard chemotherapy for HER2-low breast cancer patients, improving their rates of survival and remission.
The drug is not expected to be a cure for breast cancer, patients take the drug to keep cancer at bay as long as their bodies can tolerate the medication. However, this is the first instance of a HER2-targeting drug that can be used on the more common HER2-low breast cancer patients. It also provides for the first time an identifiable and targetable population who can immediately be isolated and delivered the drug for efficient treatment.
(Edited by Poulomi Banerjee)
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