Trojan horses, the drugs that already multiply survival in cancer patients | Health & Wellness | The USA Print

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Oncologists gathered in Chicago for the annual meeting of the American Society for Medical Oncology (ASCO) enthusiastically received the presentation of the results of the DESTINY-Breast04 study by Dr. Shanu Modi. The researcher at the Memorial Sloan Kettering Cancer Center in New York, leader of this international study that has been published in the journal New England Journal of Medicine, stated that this drug will change the way of treating breast cancer. The drug, a kind of pharmacological smart missile baptized as Enhertu, managed to double the average time in which patients with metastatic breast cancer survived without seeing the disease progress, from 5.1 months with conventional chemotherapies to 9.9 with the new therapy. Overall survival increased from a mean of 16.8 months to 23.4.

The drug is actually a combination of drugs (trastuzumab and deruxtecan) that combine their abilities and work as a sort of Trojan horse. Deruxtecan is a toxic product, similar to traditional chemotherapy, which prevents the development of cancer, but also damages healthy cells in the body. Trastuzumab, used for more than 20 years, is one of the first drugs directed against cancer and at the time it was already a revolution. Capable of specifically coupling to the HER2 protein, which is expressed in especially aggressive breast tumors, it is capable of destroying the tumor cell without doing so much damage to healthy ones. The new combination, developed by the pharmaceutical companies Daiichi Sankyo and AstraZeneca, uses tratuzumab to bring the destructive power of deruxtecan right up to the tumor cells, where it releases much more powerful chemotherapy locally, multiplying its effectiveness and limiting side effects.

The drug had already shown its ability to improve the expectations of patients with metastatic breast tumors that highly express the HER2 protein, to which trastuzumab binds. “The novelty is that this drug also demonstrates its activity for low HER2 patients, who were traditionally considered negative. [y fuera del alcance de fármacos como trastuzumab]”, points out Cristina Saura, a researcher at the Vall d’Hebron Institute of Oncology and co-author of the study in which the value of the new drug was tested. In this way, treatments for tumors with a significant presence of HER2, which are approximately 20% of the total, will reach more patients in whom until now the amount of this protein was considered insufficient to target these targeted drugs.

The success of this drug should also be evaluated considering that it is used with people who have already received several treatments before and, as they fail, they run out of options. “In patients who have metastatic breast cancer, the goal is to prolong patient survival as long as possible with the best possible quality of life and, when this drug is approved, it may be another way to achieve that goal,” says Saura. “It is possible that over time we will stop using conventional chemotherapies and use only [estos conjugados]”, he concludes.

The researcher from the Clinic-IDIBAPS Maria Vidal;  the head of Oncology at ICO l'Hospitalet, Miguel Gil;  the head of the Vall d'Hebron-VHIO Breast Cancer Unit, Cristina Saura;  and the head of Translational Genomics and Tumor Therapies at IDIBAPS, Aleix Prat, participants in the DESTINY-Breast04 trial
The researcher from the Clinic-IDIBAPS Maria Vidal; the head of Oncology at ICO l’Hospitalet, Miguel Gil; the head of the Vall d’Hebron-VHIO Breast Cancer Unit, Cristina Saura; and the head of Translational Genomics and Tumor Therapies at IDIBAPS, Aleix Prat, participants in the DESTINY-Breast04 trialFRANCISCO AVIA (Europa Press)

These conjugated drugs were one of the novelties presented this weekend at ASCO, an annual meeting in which the main global advances against cancer are usually announced. As is increasingly the case with this disease, there was talk of partial success against many subtypes of a disease that are actually more than 200. An example is the PANAMA trial, one of those highlighted at the meeting. The work, led by Dominik Paul Modest, from the Charité hospital in Berlin, showed that a combination of a drug called panitumumab with chemotherapy achieved an average survival of more than three years (36.2 months) in patients with a type of colon cancer metastatic with the unmutated KRAS gene. The result represents an increase of 5 months compared to the 31.3 achieved by the current reference treatment. Cathy Eng of Vanderbilt University highlighted that these results “emphasize the importance of performing comprehensive tests with biomarkers, in particular to see the type of KRAS gene that patients with this type of tumor have.”

According to Enriqueta Felip, president of the Spanish Society of Medical Oncology (SEOM), present at the congress, one of the main objectives of oncologists is, in addition to increasing survival, “to see how the quality of life of patients is improved ”. “Support treatments for all treatments, management of symptoms associated with toxicities or seeing how we improve the lives of patients who survive, how long-term effects are monitored or how they return to work”, are also aspects of the treatment of the disease, explains Felip. In this sense, in ASCO works were presented that will allow fine-tuning the treatments, to eliminate those that are unnecessary and thus reduce their side effects. A study led by Jeanne Tie, from the Peter McCallum Cancer Center in Victoria, Australia, showed that with a blood sample, known as a liquid biopsy, it is possible to see if there is tumor DNA in the circulation after surgery to remove it. Those without were able to get rid of chemotherapy and associated damage with a low risk of relapse.

Finally, one of the studies with the most striking results of those presented at ASCO was one led by Luis Alberto Díaz, from the Memorial Sloan Kettering Cancer Center in New York. in an article published in the New England Journal of Medicine, explains how it was possible to make a type of rectal cancer disappear in 12 patients with a drug called dostarlimab. This monoclonal antibody dismantles the systems with which the cancer makes itself invisible to our immune system so that it can attack and destroy it. According to Diaz in The New York Times, there is no known “other study in which the treatment completely destroyed the cancer in each of the treated patients.”

The study is small and the short follow-up time calls for taking the results with caution, so other trials will be necessary to confirm the potential of this drug in a specific type of colorectal tumor. In addition to its surprising success in making the cancer disappear, among the patients treated by Díaz and his team, the usual side effects of dostarlimab were not observed, something that also indicates that something new has happened and that more studies will be needed to understand it well.

The theme in this edition of ASCO was Advancing Equitable Cancer Treatment Through Innovation. For years, particularly with the arrival of new treatments such as monoclonal antibodies, immunotherapies or CAR-T therapies, which are very effective in some cases but extremely expensive, the price of drugs has been critical for oncologists and entities that They pay for the drugs. In previous editions of ASCO, financial toxicity was already discussed as one more side effect of cancer treatments, particularly in countries like the United States where medical coverage is not universal. Dostarlimab, for example, involves a course of eight doses over six months at $11,000 each. “It is a challenge that we all have to work on. We have to talk about the cost of the drugs”, admits Felip. The economic one is one more factor to add to the fight against a disease of devilish complexity.

Els Torreele, former director of access to essential medicines at Doctors Without Borders, who developed a medicine for a fraction of the cost that pharmaceutical companies usually attribute to it to demonstrate the arbitrariness with which drug prices are set, is more vehement in her opinion on the price of cancer treatments. “I am amazed that there are people who work in cancer, and especially people in the medical community, who are complacent about the unequal access to cancer treatments that exist in the world today,” says the now researcher at University College London. “I wonder if they would feel the same if a member of their family was denied access to potentially life-saving treatment just because business leaders and shareholders of companies on the other side of the world have decided that their monopoly and their commercial interests are more important than making drugs affordable, and they have the power to say: too bad if you need these drugs now, we may make them more affordable in ten or twenty years’ time,” he says.

“Now we know that the exorbitant prices charged by companies for new cancer therapies are largely arbitrary, and totally independent of production costs or the expenses involved,” continues Torreele, who emphasizes the public effort to finance part of the research that gives rise to new therapies. “Drug development is a massively collective effort and it is not normal for only one actor in the entire value chain to obtain the rights to availability, pricing and access, as is the case today,” she adds. And it concludes with a plea in favor of an innovation that reaches more people as soon as possible: “We need transparency and a fairer recognition of the contributions of the different actors in the process, and ensure that the ultimate goal of medical innovation is equitable access and not the economic return.

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