Advance in lung cancer treatment: 81% reduction in progression

In a major advance for the treatment of advanced non-small cell lung cancer (NSCLC), Pfizer announced encouraging results from its Phase 3 clinical trial. This study compares a third-generation ALK inhibitor with a first-generation one, demonstrating that Most patients treated with the new therapy can live more than five years without disease progression.

These results were presented at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting and published in the Journal of Clinical Oncology, highlighting the importance of this advance in oncology.

An ALK inhibitor is a substance that blocks the activity of anaplastic lymphoma kinase (ALK), a protein that helps control cell growth. By blocking this protein, it is expected to prevent the formation and spread of cancer cells, providing a crucial tool in the fight against certain types of lung cancer.

The study followed patients for five years and demonstrated an 81% reduction in the rate of disease progression or death among those treated with the third-generation ALK inhibitor, compared with those who received the first-generation inhibitor. In addition, 60% of patients treated with the new therapy were alive without disease progression after five years, compared with only 8% of patients who received the first-generation drug.

Dr. Diego Kaen (MP 1898), Head of Clinical Oncology and Research at the Centro Oncológico Riojano Integral (CORI), stressed to El Litoral the relevance of these findings: “We are talking about the fact that 10 years ago, a patient with an advanced stage of the disease did not survive more than six months.”

The impact of this breakthrough is particularly notable in a context where lung cancer remains the leading cause of cancer-related death worldwide. In Argentina, it is the cancer with the second highest mortality rate, surpassing breast, colorectal, pancreatic and prostate cancer.. Every year, around 13,000 new cases of lung cancer are diagnosed in the country, representing 9.8% of all cancer cases.

Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases.and 3-5% of these cases have alterations in the ALK protein. Patients with ALK-positive advanced NSCLC are usually young and often develop brain metastases, which can occur in 25-40% of cases within two years of the initial diagnosis.

The third-generation ALK inhibitor showed a 94% reduction in the risk of developing brain metastases compared to the first-generation inhibitor. In the study, only 4 of 114 patients who received the newer therapy developed brain metastases within the first 16 months of treatment, compared with 39 of 109 patients who received the older therapy.

“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 live more than five years.and move forward without progression of the disease,” said Diego Kaen.

The professional highlighted the importance of this advance in the treatment of advanced ALK-positive NSCLC. “It is a disease with a very high mortality rate. 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 dealing with a chronic disease.”

“ALK-positive advanced NSCLC is typically aggressive and often affects young people in the prime of their lives,” Kaen continued. “This updated analysis shows that the third-generation ALK inhibitor helped patients live longer without disease progression, with the majority of patients experiencing sustained benefit for more than five years, including nearly all patients who had protection from disease progression in the brain. These improvements in outcomes for patients with ALK-positive NSCLC represent a remarkable advance in lung cancer.”

The doctor further explained: “You have to understand that this was a disease where 100% of patients died within four or six months 7 or 8 years ago. Today, with third-generation ALK inhibitors, we have 62% of patients alive at five years, and the curve continues, which means that these patients will probably live much longer than five years. We must always understand that we are talking about stage 4 lung cancer, which is the disease that causes the most deaths worldwide. The fact that 60-62% of patients are alive without disease progression means that they have no symptoms and that the disease is stabilized or in complete response.

Roger Dansey, MD, Director of Oncology Development at Pfizer, noted that “These trial results CROWN “This is unprecedented, as the majority of patients receiving the third-generation ALK inhibitor are living more than five years without disease progression.” This breakthrough reflects Pfizer’s commitment to developing innovative therapies that significantly improve the lives of patients.

Dr Benjamin Solomon, Department of Medical Oncology at the Peter MacCallum Cancer Centre and principal investigator of the CROWN trial, said: “The third-generation ALK inhibitor helped patients live longer without disease progression, and the majority of patients experienced sustained benefit for more than five years, including nearly all patients who had protection from disease progression in the brain. These improvements in outcomes for patients with ALK-positive NSCLC represent a remarkable advance in lung cancer.”

Treatment with the third-generation ALK inhibitor also demonstrated a safety profile consistent with previous studies, with no new safety signals. The most common adverse events (≥20%) reported in patients treated with the new therapy included edema, weight gain, peripheral neuropathy, cognitive effects, mood effects, diarrhea, dyspnea, arthralgia, hypertension, headache, cough, pyrexia, hypercholesterolemia, and hypertriglyceridemia.

Grade 3/4 adverse events occurred in 77% of patients on third-generation therapy, compared with 57% of patients on first-generation therapy. Permanent discontinuation of treatment due to adverse events was similar in both groups, at 5% and 6%, respectively.

Early diagnosis is key to improving success rates in lung cancer treatment. Dr. Kaen stressed the importance of regular screening, especially for patients with risk factors such as smoking or a family history of cancer. “If someone is a smoker or has a family history of any type of cancer, they should go to their family doctor and get tested. Early detection can lead to more effective treatment and significantly improve prognosis,” the professional emphasized.

Essay CROWN marked a milestone in treatment of advanced ALK-positive NSCLC, offering new hope to patients and their families. The possibility of making the disease chronic and living more than five years without disease progression is a notable advance in the fight against lung cancer. These results underscore the importance of continued research and development of new therapies to improve the quality of life and survival of cancer patients.

Kenneth Culver, Director of Research and Clinical Affairs at the non-profit organization ALK Positive, concluded: “These new results from the CROWN trial symbolize significant progress in front-line treatment for ALK-positive lung cancer, which led to notable improvements for the patient community.