EGFR, the new clue in lung cancer to increase patient survival

In lung cancer there are many obstacles to overcome to prevent more than 22,400 people in Spain from losing their lives due to this disease. First, tobacco and its new forms of addiction, vaping and electronic cigarette. Second, an early diagnosis of the disease, since half are detected with a very advanced tumor. Data from the Spanish Lung Cancer Group indicate that 31,000 new cases are diagnosed each year and that their incidence is on the rise.

With this panorama, the search for therapeutic strategies is vital to reduce mortality figures. Having clues about how and with what to treat patients and establishing new treatment schemes have an impact on both patient survival and quality of life.. At the Congress of the American Society of Clinical Oncology (ASCO), the use of a drug, osimertinib, has been valued, which used instead of chemotherapy after performing surgery to remove the tumor in a specific type of patients increases survival .

Specifically, these are patients diagnosed at an early stage with non-small cell lung cancer, which are 85% of cases, and who also have the mutated EGFR protein. Margarita Majem, an assistant physician in the Medical Oncology Service of the Hospital de la Santa Creu i Sant Pau, explained to this medium that “in absolute terms, at least 250 patients a year in Spain would benefit from this progress.”

Arriving at this accounting requires taking into account the profile of the candidates, which is what has been observed in the Audara study, the results of which have been presented these days at ASCO and have also seen the light of day in The New England Journal of Medicine.. “These are mostly women patients, 70% non-smokers or ex-smokers or occasional users,” explains Majem.

One of the positive points is that the study ends the skepticism of the scientific community regarding a treatment scheme for small cell lung cancer with non-squamous histology.. The latter refers to flat cells that look like a fish scale under a microscope and whose presence is essential when deciding on treatment.

How is the new approach?

Thus, the new approach consists of giving osimertinib to patients who have undergone surgery to remove most of the tumor in their lungs instead of chemotherapy.. “It is an adjuvant use,” says Majem. “A way to avoid its toxicity, but only in those patients who have a determined mutation in the EGFR gene.”

Once again, in Oncology it is a question of specifying even more who should receive a treatment in order to optimize its use both in terms of benefits for the patient and cost effectiveness.. Study author Roy S.. Herbst, explained at a press conference the percentages of the population by geographical area in which there was a proportion of patients with the mutated EGFR gene. “We can find between 10-25% in Europe and the entire American continent, and about 40% in Asia and Australia,” said the chief of Medical Oncology at the Yale School of Medicine and director of the Yale Cancer Center.

Herbst further noted that “Adaura is the first global phase III study to find statistically significant disease-free survival, that is, the amount of time after treatment that no signs of tumor are found.”. The data from the study show that the risk of mortality is reduced by up to 51% compared to the group that received placebo.

From ASCO, Nathan Pennell, from the Cleveland Clinic, explains that “we have been using adjuvant chemotherapy as a single option for all lung cancer patients despite a decade of advances in targeted treatments for selected groups of patients.”. It should be noted that osimertinib already has the approval of regulatory agencies, both in the US and in Europe, and has also been available in Spain for about six months.

“For the first time in the field of lung cancer, adjuvant osimertinib unequivocally improves survival in people with resected EGFR-mutant non-small cell lung cancer.”. This should be the new standard of care for these patients,” Pennell stresses.

Majem stresses that it is a new approach for a specific profile of patients in which good results are obtained both in terms of quality of life “there is less toxicity because we do not use chemotherapy” and “we offer more survival”. However, he stresses that what is important is that “a post-surgery test be carried out in the clinic to look for patients with mutated EGFR, who are the target of osimertinib [drug developed and marketed by AstraZeneca]”.

What if we treat the tumor before operating?

This same week The New England Journal of Medicine published another way to tackle non-small cell lung cancer in early stages from another perspective: before the operation. “We have to take into account all the possibilities to give patients the best option. And trying to shrink the tumor before the operation is also a key resource,” explains Majem, also a participating author on this study.

Thus, on this occasion, the aim is to adjust the use of pembrolizumab to a patient profile “mostly men, ex-smokers and smokers (important in this order) and with few molecular alterations”, Majem highlights.

The use of this drug, whose mission is to bind to the PD-1 protein to help immune cells destroy more cancer cells, serves to obtain better responses from patients to previous treatments. “Until now, the use of chemotherapy beforehand only improved overall survival by 5% at five years.. Bearing in mind that it is always the option that can cause the most toxicity in patients,” explains the oncologist at Hospital Sant Pau.

In conclusion, the NEJM authors state that “among patients with this early-stage resectable lung tumor, neoadjuvant pembrolizumab added to chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, led to a pathological response.” treatment compared with neoadjuvant chemotherapy alone followed by surgery.