Researchers at the Vall d’Hebron Institute of Oncology (VHIO) have had a prominent presence at the annual congress of the European Society for Medical Oncology (ESMO), which is being held in Paris from September 9 until today. Thus, the VHIO has played a leading role in several trials advancing new treatment options in metastatic colorectal cancer and which have been presented in Paris over the last few days.
Colorectal cancer is one of the most common, which affects men and women equally, and with special relevance. from the age of 50 onwards. Although it is the third leading cause of cancer-associated deaths, in recent years, it has been possible to decrease its mortality rate significantly. However, when the disease reaches the metastatic stage, the prognosis worsens greatly and the survival rate drops from the 91% at five years of age, when it is detected locally, to the 17%.
Thus, much of the research efforts in cancer have focused on seeking new alternatives to improve these results. The following are some of the most prominent trials.
Encorafenib and cetuximab in combination with chemo for the first time as first-line treatment.
The BRAFV600E mutations mutations are found in approximately 10% of metastatic colorectal cancers. Although it is a rare mutation, it is associated with a negative prognosis. Patients with this mutation are generally resistant to therapies and develop resistance to treatments very quickly, and no substantial advances in their treatment had been made until recently. In 2019, the BEACON CRC trial, led by Josep Tabernero, director of VHIO and head of the Medical Oncology Service at Vall d’Hebron, demonstrated that the targeted therapy including BRAF (encorafenib) and EGFR (cetuximab) inhibitors. was effective in achieving a overall survival significantly longer overall survival and a higher response rate than standard therapy in these patients. Thus, the dual combination became a second- and third-line treatment option for this group of patients and was approved in most countries.
Although efficacy data are not yet mature because they were not the subject of these early phases of the study, it has been seen a promising antitumor activity to all patients who have received the different drug combinations that justify the continuation of the Phase III study, which is already underway. “The great novelty of this study is that. for the first time this combination of treatments is being evaluated in the first line, since until now it had only been tested in more advanced stages of the disease, when patients had already progressed to other treatments,” explains Tabernero.
FRESCO-2 Study: A Novel VEGFR Inhibitor
In colorectal cancer, the growth factor of the vascular endothelial growth factor or VEGF plays a very decisive role, since it promotes the angiogenesis or appearance of new capillaries. In this way, the tumor reaches the necessary nutrients for further growth. For this reason, in recent years a number of different types of inhibitors of VEGF receptors or VEGFR have been developed in recent years. By blocking them, it is hoped to cut off this growth pathway and thus control or even eventually reduce tumor size.
One of the latest VEGFR inhibitors that have been tested is the fruquintinib, a tyrosine kinase inhibitor that blocks receptors 1, 2, and 3. This drug has already been evaluated in China, in heavily pretreated metastatic colorectal cancer patients, and the good results of the FRESCO-1 study served to continue its development into a international study, the FRESCO-22 study, which is the one now being presented. “Being a well-tolerated treatment, and given the consistency of the results of both trials, we are very possibly looking at a promising new opportunity for metastatic colorectal cancer patients”, says Dr. Elena Élez, one of the authors of the study.
A promising option for refractory HER2-expressing patients.
Patients with metastatic colorectal cancer who overexpress the HER2 protein are not many, between 3% and 5%. But this does not preclude that they are being sought and developed. treatments that can use this overexpression as a target. This is the case of the combination of tucatinib (a kinase inhibitor that induces HER2-driven cancer cell death) and trastuzumab (a monoclonal antibody that binds to the HER2 protein and prevents tumor cells from dividing and growing). The safety and efficacy results of the MOUNTAINEER3 clinical trial evaluating this combination have just been presented at the ESMO meeting.
“HER2-expressing chemotherapy refractory patients achieve a limited clinical benefit with current therapies. The results obtained now lead us to be optimistic that the combination of tucatinib and trastuzumab has the potential to become a new therapeutic option.” Élez explains.