Lung cancer is the leading cause of cancer death worldwide, accounting for almost one in five cancer deaths (19%). And as long as the main risk factor, tobacco, is not restricted, the mission of oncologists is to find the infallible formula to corner the tumor cells that little by little take over the respiratory organs and their surroundings to extend the lives of patients.
«Lung cancer is not a single tumor, but a set of very different and heterogeneous tumors. The challenge is that treatments must be highly personalized to be effective,” explains Mariano Provencio. The president of the Spanish Lung Cancer Group (GECP) and head of the Medical Oncology Service at the Puerta de Hierro University Hospital in Madrid outlines the main advances against the different faces of respiratory tumors and the clinical needs they pose.
Within the framework of the Congress of the European Society of Medical Oncology (ESMO), held these days in Madrid, two studies that challenge a systemic disease at the time of diagnosis have been presented in the most relevant sessions of the event. Specifically, the tumor called small cell lung cancer (SCLC). It is a type that "represents approximately 15% of cases," says Provencio, and around two-thirds of patients are diagnosed with advanced disease, "which is a challenge," he adds.
This is because it is a very aggressive tumor, whose expansion to the rest of the organs, surrounding or not, is rapid; which leads to dissemination to other locations, such as the brain and liver, "which compromises the lives of patients," explains the president of the GECP.
New approaches against lung cancer with "fantastic results"
Provencio puts on the table two formulas with "fantastic results." For small cell cancer, responsible for some 200,000 deaths worldwide, - "which had been almost 30 years without significant progress and with prognoses of just months" -, comes an innovative combination of two drugs: tarlatamab with durvalumab, in first-line treatment, "which has managed to double survival, now allowing us to talk about years of life," highlights the oncologist.
The data from this advance have also been published in The New England Journal of Medicine and highlight that the combination reduced the risk of death by 58% as a long-term treatment in patients with advanced disease. This translates into survivals that almost reach two years (21.1 months), compared to just over one (12.7) that is achieved with durvalumab alone.
The combination of tarlatamab with durvalumab aims to hijack the patient's own defenses (T lymphocytes) and force them to attach and destroy tumor cells that have the mark of the DLL3 protein. And therein lies the key, because being a protein found on the surface of certain cancer cells (especially in some aggressive types of respiratory tumors), it functions as a distinctive mark of the tumor. "The aim is for the body's immune system to recognize and attack tumors in a much more precise way than traditional chemotherapy," explains Provencio.
Through the advanced phase study (3) called DeLLphi305, it has been concluded that "an orphan tumor of targeted therapies now has an option that changes the landscape of the disease." We have gone from chemotherapy and, years later, immunotherapy, as the main resources in the therapeutic kit, which "added some benefit, but modest," to a "great leap in quality in survival," argues the oncologist.
For those patients with lung cancer with mutations in EGFR (the factor responsible for its lack of control) that progress, where before doctors were disarmed when the response to treatment stopped, Provencio now comments that "we have the molecules that interfere with tumor resistance mechanisms, which allows us to increase survival and disease-free time."
Here he mentions the Safron study, also in an advanced phase (3), which highlights the results of another combination: osimertinib plus savolitinib reduced the risk of disease progression or death by 45% and the risk of death by 32% in lung cancer with EGFR mutation and MET-mediated resistance. This translates into an approach that stops cells from growing uncontrollably and without the tumor having the opportunity to learn how to get rid of the drug that is eliminating it. "The treatment interferes with one of the resistance mechanisms of the disease," says the oncologist.
Challenges in the clinic after arrival
One of the conditions for transferring laboratory results to daily clinical care is how the health system must face the challenge of having to routinely determine the molecular resistance mechanisms of patients when their disease progresses. "In addition to a conventional or 'usual' initial evaluation, it is necessary to perform molecular diagnoses to precisely identify what is failing in the tumor," Provencio recalls.
With all these advances, one step away from the consultation, the diagnosis must also be reformulated: this requires specifically analyzing and determining the resistance mechanisms in those patients whose disease progresses, allowing us to know the "last names" of the tumor "to direct immunotherapy or targeted therapy in a highly specific manner."
