He Hospital October 12 He has led an investigation and has participated in another against two types of lung cancer. One of them is a international clinical trial in which a test has been drug that acts against a subtype of an oncogenedenominated KRASwhich has the greatest impact on the origin of human tumors and which generates a protein involved in the multiplication, maturation and destruction of the body’s cells.
This study, published in the international scientific journal The Lancethas focused on most common lung cancerthe one of non-small cells. Thus, the Codebreak 200 clinical trial compared treatment with sotorasib with standard treatment (docetaxel) in patients with non-small cell lung carcinoma, carriers of the KRAS G12C mutation, who had been treated with one line of treatment. standard chemotherapy/immunotherapy.
The cases of 345 patients, from 148 centers in 22 participating countries, 12 of them Spanishincluding the Puerta de Hierro, Ramón y Cajal and La Paz hospitals in Madrid, as well as the 12 de Octubre Hospital as research coordinator.
The results have shown a reduction of the 34 % in the rate of tumor progression throughout the study period and an increase in the response rate, all accompanied by a favorable safety profile with a significant decrease in adverse effects.
After 40 years of trials
Cancer research has spent more than 40 years trying to develop drugs against the KRAS oncogene. According to Luis Paz Ares, head of the Medical Oncology Service at Hospital 12 de Octubre and principal investigator of this clinical study, have “demonstrated in a phase 3 trial that a specific KRAS inhibitor drug works.” Sotorasib already represents “a new treatment opportunity for patients”, while “opening a door to continue researching and trying to optimize the type of therapy against KRAS that seemed very difficult, if not impossible.”
The first study, led by Hospital 12 de Octubre, included 345 patients from 148 centers in 22 countries, 12 of them Spanish.
The drug has already been approved for the treatment of recurrent lung cancer by the FDA (Food and Drug Administration) in the United States and by the EMA (European Medicines Agency) in Europe.
Immunotherapy
The second investigation against lung cancer in which the Oncology Service of Hospital 12 de Octubre has participated is within the new immune-type therapies. This has consisted of the initial evaluation of the first molecule that activates the cells immunelas T cellsagainst lung cancer small cells, the most aggressive of these tumors.
This is a phase 1 trial on 107 patients that has shown relevant referral rates of more than 23% in cases previously treated with other therapies, with average duration of answer that exceeded 12 monthswhich, if these promising results are confirmed, would mean great potential for improving patient survival.
Small cell lung cancer is an aggressive malignancy, accounting for 15% of lung tumors
This drug treatment called tarlatamab is administered by intravenously, once every one to two weeks, and belongs to a class of drugs called “bispecific T-cell activators” (BITEs). Its name comes from the fact that it consists of two specific ends: one attaches to the patient’s lung cancer cell by binding to a specific protein, while the other T-end binds through a receptor to the T lymphocytes of the patient.
As a “bridge” or “matchmaker” in the words of Paz-Ares, tarlatamab connect tumor cell with the patient’s own T cells, which become activated and use a variety of mechanisms to attack and destroy the cancer cell.
The most aggressive tumor
lung cancer of small cells It is an aggressive malignancy, accounting for 15% of lung tumors. Despite being a disease initially sensitive to chemotherapylas responses are usually temporary and the prognosis is poor, with 3-year survival rates of 6% for patients with this type of disseminated tumor.
These two drugs could be at the forefront of cancer research aimed at personalized medicine
According to Paz-Ares, “there have been very few changes in the treatment of this disease in recent decades, so having a drug for previously treated patients, such as those included in this study, is important news,” both for patients as for doctors accustomed to dealing with the disease.
“We believe that we are witnessing the birth of a new class of therapies for solid tumors”, indicates the researcher.
Both studies at Hospital 12 de Octubre include of drugs of the biotech company Amgen and are part of the Vanguard from cancer research aimed at personalized medicine: “having greater biological knowledge of diseases allows us to use part of this information, mutations, the expression of certain proteins, as biomarkers to select therapies for each specific patient”, concludes the oncologist.
REFERENCES:
L. Paz-Ares et al. “Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial”.The Lancet (2023).
Owonikoko, T. et al. “Tarlatamab, a First-In-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small Cell Lung Cancer: An Open-Label, Phase I Study”. Journal of Clinical Oncology (2023).
Hospital October 12
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