He lung cancer is the main death cause for cancer both globally as in Latin America, representing 12% of all deaths from this diseaseaccording to World Health Organization (WHO). This is because a high percentage of cases are diagnosed in advanced stages, when treatment options are limited.
In Argentina, It is the second with the highest mortality, above the breast, colorectal, pancreatic cancer and that of prostate. In turn, it is the fourth in incidence, with around 13 thousand new cases per year.
He smoking It is responsible for 85% of lung cancer diagnoses. A worrying fact is the increase in the incidence and mortality of this cancer among women in recent years, in contrast to the decreasing trend among men in the last decade. This could be explained because the women They began smoking in the 1970s and 1980s, a period some experts call the “epidemic of women smokers.”
Scientists have been researching therapeutic options for years to mitigate the effects of cancer and extend the survival of patients after diagnosis.
Pfizer Inc. now announced long-term results from the Phase 3 CROWN trial, which evaluates a third generation ALK inhibitor available in Argentinacompared with a first-generation one in people with previously untreated ALK-positive advanced non-small cell lung cancer (NSCLC).
After five years of follow-up, study showed an 81% reduction in the rate of disease progression or death with the third-generation ALK inhibitorcompared to the first generation.
Besides, 60% of patients treated with the newer therapy were still alive without disease progression after five years, compared to 8% of those treated with the first generation drug. These data were presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 and published in the Journal of Clinical Oncology.
“These results from the CROWN trial are unprecedented, as the majority of patients receiving the third-generation ALK inhibitor are living more than five years without disease progression,” said Roger Dansey, MD, Chief Development Officer, Oncology. , Pfizer.
And he added: “These results are an excellent example of Pfizer’s long-standing commitment to discovering and developing scientific advances for patients, and support our therapies as a standard of care for the first-line treatment of people with ALK-positive advanced NSCLC. ”.
Lung cancer non-small cell (NSCLC) constitutes approximately the 80-85% of lung cancers, and tumors with alterations in the ALK protein are found in approximately 3-5% of NSCLC cases.
Between 25-40% of people with ALK+ advanced NSCLC may develop brain metastases within within two years after the initial diagnosis. Pfizer has developed a therapy aimed at specifically inhibiting the mutated ALK protein, including resistance alterations caused by other ALK inhibitors and with a greater ability to penetrate the blood-brain barrier.
In this sense, Dr. Diego Kaen (MP 1898), Head of Clinical Oncology and Research at the Riojano Integral Oncology Center (CORI) stated: “We are talking about the era of cancer chronification. 10 years ago, a patient with an advanced stage did not live more than six months, and today more than 50% in those same conditions can survive five years and continue without progression of the disease.”
Likewise, he added: “It is a disease with very high mortality. In fact, it is the one that causes the most deaths worldwide, but fortunately we are beginning to have concrete and reliable data that, in the face of some molecular subtypes of lung cancer, we are already facing a chronic disease.”
Kaen referred to Infobae Regarding the main differences in the effectiveness of the third-generation ALK inhibitor compared to the first: “Compared to the first generation, you clearly have 60% of patients alive without disease progression. In other words, they continue with the initial disease at 60 months, at five years, and the median has not yet been reached. That is, it is clear that we cannot talk about healing yet. But regarding the chronification of lung cancer, the CROWN study in the first line of patients with ALK-positive lung cancer is the clear example that it is.”
“ALK-positive advanced NSCLC is usually aggressive and often affects young people in the prime of their lives”said Benjamin Solomon, MBBS, Ph.D., Department of Medical Oncology, Peter MacCallum Cancer Center, and Principal Investigator of the CROWN trial.
“This updated analysis shows that the third-generation ALK inhibitor helped patients live longer without disease progression.”, and most patients experienced sustained benefit for more than five years, including almost all patients had protection against disease progression in the brain. “These improvements in outcomes for patients with ALK-positive NSCLC represent a notable advance in lung cancer,” she added.
In this updated analysis, the third-generation ALK inhibitor showed a 94% reduction in the risk of intracranial progression (HR, 0.06; 95% CI, 0.03-0.12).
The median time to intracranial progression was not reached with the third-generation inhibitor (95% CI, NR-NR), while it was 16.4 months (12.7-21.9) with the first-generation inhibitor. generation. Among people without brain metastases at baseline who received the newer therapy, only 4 of 114 developed brain metastases in the first 16 months of treatment, compared with 39 of 109 patients who received the older therapy.
At the time of analysis, 50% of patients in the CROWN trial were still receiving the third-generation inhibitor, compared with 5% of patients receiving the first-generation treatment.
“Although ALK-positive advanced NSCLC accounts for approximately five percent of all NSCLC cases, this translates to 72,000 people being diagnosed worldwide each year,” said Kenneth Culver, Director of Research and Clinical Affairs at the nonprofit organization ALK Positive.
“These new results from the CROWN trial symbolize significant progress in front-line treatment for the targeted treatment of ALK-positive lung cancer, which has led to notable improvements for the patient community.”
The safety profiles of both drugs at the five-year follow-up were consistent with previous studies, with no new safety concerns. In this analysis, the most common adverse events (AEs) (≥20%) in patients treated with third-generation therapy were similar to those reported in 2020 in the CROWN trial.
These include edema, weight gain, peripheral neuropathy, cognitive and mood problems, diarrhea, shortness of breath, joint pain, hypertension, headache, cough, fever, high cholesterol and triglyceride levels.
Serious adverse events (grade 3/4) occurred in 77% of patients with third-generation therapy and 57% of patients with first-generation therapy.
Adverse effects led to permanent treatment discontinuation in 5% of patients on third-generation therapy and 6% of patients on first-generation therapy.
How has the availability of the third-generation ALK inhibitor impacted the treatment of patients with advanced NSCLC in Argentina? he asked. Infobae.
“Until now in Argentina, third-generation inhibitors could be used in the first line. But, in public hospitals and in areas with little access it was not yet a standard, there was difficulty in obtaining it. These data from this CROWN study already support the use of this drug as the first line in these patients. Such a curve has never been seen in advanced lung cancer: between the second and fifth year in patients, the curve is almost flat. We are talking about stage four and ALK positive lung cancer, of worse prognoses. Ten years ago, None of these patients lived more than six months.said Dr. Kaen.
Early diagnosis also contributes to the success of lung cancer treatment. That is why it is essential to undergo periodic studies to identify the tumor at an early stage.
“Finding this disease early, detecting it in time and taking it to surgery is what achieves a cure. When it is advanced metastatic, as in the case of the CROWN study, we are already talking about chronification. In other words, it is still essential to aim all weapons, public, private, political, and non-political tools, to detect lung cancer early. And for that, the at-risk population must first be detected. That is, those patients who smoke, with a family history, with COPD, have a low annual CT scan as screening for lung cancer,” Kaen concluded.