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Friday, April 12, 2024

We are waiting for a combined scheme

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Interview with prof. Jakub Kucharz from the Urinary Tract Cancer Clinic of the National Cancer Institute – “The combination of an antiangiogenic drug with an immunocompetent drug gives the highest percentage of objective responses; in the largest percentage of patients it causes a significant reduction in tumor mass.”

Kidney cancer accounts for almost 2%. malignant tumors were diagnosed. In Poland, approximately 5,000 new cases are registered annually; the number of cases increases by 2-3% every year, and this increase is especially noticeable in men. Why do men get sick more often?

Gender is an independent risk factor for the disease; men get sick more often. Risk factors also include: smoking, drinking alcohol, taking certain painkillers, obesity and hypertension. However, these are only risk factors; of course, women who do not smoke, do not drink alcohol and have a slender physique can also get sick. We have no effect on gender, but it is worth minimizing modifiable risk factors, such as smoking, drinking alcohol, obesity, hypertension.

It is also worth noting that the genetic basis of kidney cancer is rare: 97%. cases are so-called sporadic, i.e. not associated with genetic load.

Cancer diagnosed at an early stage has a better chance of being cured; What can be done to diagnose kidney cancer at an early stage, when it has not yet reached an advanced stage with metastases?

Metastatic disease is initially diagnosed in 20-30%. Patients. In the vast majority of cases, cancer is limited to the kidney at the time of diagnosis. In more than half of cases, it is diagnosed accidentally during imaging studies of the abdominal organs, most often ultrasound. It is definitely worth carrying out such an examination from time to time, especially if there are alarming symptoms in the abdominal cavity or urinary system, and also when the general practitioner recommends an ultrasound of the abdominal cavity.

How do you assess the current treatment options for advanced kidney cancer in Poland? What positive changes have occurred recently?

Treatment options have improved significantly since May 2022 – we have a new program for B.10 since then. This allows the vast majority of patients to comply with the recommendations for diagnostic and therapeutic procedures prepared by the Polish Society of Clinical Oncology and the Polish Society of Urology. The drug program is modern; three lines of treatment for advanced kidney cancer are available.

From September 2023, we also have the option of using adjuvant treatment – ​​in the case of kidney cancer without metastases or metastatic disease after radical local treatment of metastatic disease. We are missing one more element – the combination of immunotherapy with a multikinase inhibitor, i.e. with an antiangiogenic drug. Currently, either dual immunotherapy or an antiangiogenic drug can be used. We do not have the ability to use a combination of an antiangiogenic drug and immunotherapy in patients.

What is the advantage of combination treatment based on two drugs with different mechanisms of action? What are the clinical benefits of this treatment?

This is not so much about the advantages of such a treatment regimen, but about the possibility of personalizing treatment. For each group of patients, a slightly different treatment option will be optimal. It cannot be said that a combination of drugs based on two different mechanisms of action has an advantage over immunotherapy with two drugs. I would rather say that this is treating a slightly different group of patients.

Combining an antiangiogenic drug with an immunocompetent drug produces the highest objective response rate; in the largest percentage of patients this causes a significant reduction in tumor mass. This combination of drugs begins to work very quickly. Dual-drug immunotherapy often takes longer to see treatment effects. In patients with more severe disease symptoms and larger tumor burden, time is of the essence; Therefore, we would prefer to use a combination of an immunocompetent drug with a multikinase inhibitor in them. In the case of this option, there appears to be some synergy of action.

Would this regimen be more beneficial for some patients?

The emergence of such a combination treatment option would be another step towards further individualization of treatment. In patients in whom we want to achieve a rapid response to treatment due to large tumor burden, we are now more likely to choose an antiangiogenic drug as monotherapy; However, we would like to be able to use a combination of the two drugs.

The biological effect of immunotherapy appears later than the effect of the antiangiogenic drug; an antiangiogenic drug potentially affects the tumor microenvironment and allows lymphocytes to more effectively target the tumor. In a sense, the antiangiogenic drug “paves” the way for the immune system.

Could combination treatments be associated with more serious side effects?

Not necessary. Of course, side effects of both antiangiogenic drugs and immunotherapy may occur. Each of these forms of treatment has some characteristic side effects, but there are also side effects common to both groups. This could be, for example, diarrhea. A dilemma then arises as to which drug caused the diarrhea, since diarrhea after antiangiogenic drugs is treated differently than after immunotherapy. Therefore, the use of combination therapy certainly requires experience and skill in the use of combination therapy.

What are the recommendations of international scientific societies on this matter: the European Society of Urology, ESMO, NCCN, as well as the Polish Society of Clinical Oncology?

The combination of an antiangiogenic drug with immunotherapy is included in all international recommendations, as well as in Polish recommendations – the Polish Society of Clinical Oncology and the Polish Society of Urology. In Polish guidelines, the use of this regimen is limited to a group of patients with an intermediate and poor prognosis; European guidelines recommend ESMO for all patient groups.

We chose this solution in the Polish guidelines because no study has so far shown that the combination of two drugs with different mechanisms of action in patients with a favorable prognosis will lead to a longer overall survival than the use of these drugs separately, i.e. consistently (which we, of course, could have done in Poland for a long time). Therefore, it seems that such intensive treatment of patients from the group with a favorable prognosis is not justified, since the effect is the same, but there is a risk of increased side effects.

However, in Poland there is obviously no possibility of using drugs with two different mechanisms of action in patients with an intermediate and poor prognosis. There are three such combinations in international recommendations. At the moment there is no access to any of these schemes in Poland, and we are really looking forward to it.

Source: Directly
  • Cancer
  • Patient area

Source: Wprost

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