Taking one pill daily was able to keep advanced lung cancer under control for seven years in more than half of the patients participating in the clinical trial. This result, considered unprecedented for this disease, was achieved with the drug lorlatinibe, developed to combat tumors with a specific genetic mutation.
The study, published in September 2026 in the scientific journal Annals of Oncology, represents a seven-year update of the Phase 3 CROWN clinical trial. The results showed that 55% of patients receiving lorlatinibe remained alive and without disease progression after this period.
Two hundred ninety-six people with advanced non-small cell lung cancer positive for the ALK genetic mutation participated in the study. Out of the total number, 149 patients received lorlatinibe, and 147 received crizotinib, another drug used against this type of tumor.
In the group receiving the newer treatment, the median progression-free survival was not reached even after seven years of observation. Among patients treated with crizotinib, this figure was only 9.1 months, and the probability of remaining alive and progression-free after seven years in this second group was 3%.
Researchers also calculated an 81% reduction in the risk of disease progression or death among patients taking lorlatinibe compared to crizotinib. This result marks a significant breakthrough in the treatment of advanced lung cancer.
However, the drug is not suitable for all patients and faces access issues in Brazil. A key feature of the drug is its ability to penetrate the blood-brain barrier, a structure that protects the brain and hinders the penetration of many substances, including some medications. This is critical because patients with advanced lung cancer can develop brain metastases. Lorlatinibe was designed to act in such cases as well as to combat resistance mechanisms that can reduce the effectiveness of previous treatments.
The seven-year study results confirm this potential. No new cases of intracranial progression were registered in the CROWN study after the first 30 months of lorlatinibe treatment. Among patients who reached the end of the first two years without disease progression, the estimated probability of remaining alive and without cancer relapse in the seventh year was 79%.
This progress is particularly noticeable when compared to alternatives available in previous generations. For decades, chemotherapy was one of the main ways to treat advanced lung cancer. With the advent of ALK inhibitors, doctors have gained more targeted drugs capable of prolonging disease control.
Oncologist Gustavo Schwartzman from Sírio-Libanês Hospital noted that the evolution is visible in the results obtained from different generations of drugs. He stated: 'Never before did people live more than five years without disease progression when only chemotherapy existed. With first-generation inhibitors, it was for 5% or 10% of patients; with the second generation—20% to 30%; now we have reached 55%. The progress is huge, and we see a massive step forward in the patient's daily life.'
Oncologist Steven Stefani also emphasized the importance of long-term follow-up to assess treatment efficacy. He commented: 'The difference in effectiveness becomes very obvious when you see this analysis over seven years, and it is a significant result for the patient.'
Mateus Henrique Dias, a biomedical researcher of cancer drugs in the Netherlands, also finds the results promising. He stated: 'For those who have this specific mutation, this will truly be a big change.'
Despite the enthusiasm, there is a caveat: data on overall survival are not yet mature. This means the study has not yet accumulated enough deaths to conduct a final analysis of this indicator. Therefore, the results demonstrate long-term disease control but do not allow us to claim that the drug is a cure for advanced lung cancer.
It is also necessary to analyze the effectiveness of lorlatinibe considering side effects. In the seven-year CROWN update, 77% of patients taking the drug reported adverse events of grade 3 or 4. In most cases, these events were not necessarily caused directly by the treatment. The analysis also showed that 34% of participants had to reduce the drug dose at some point. Nevertheless, the long-term effectiveness was similar between patients who reduced the dose and those who did not require this adjustment.
Another important aspect relates to the impact on the central nervous system. Safety data collected in various clinical trials show that such a reaction can occur in 52% of patients taking lorlatinibe. Manifestations include cognitive impairment, mood changes, speech problems, sleep disturbances, and, in some cases, more serious psychiatric symptoms. The CROWN analysis over five years registered CNS events in 42% of participants receiving lorlatinibe, most of which were classified as mild or moderate.
For Mateus Henrique Dias, scientific progress must be accompanied by attention to patients' quality of life. He noted: 'We see that there are still some aspects that need to be considered. It is important for people to live, but it is also very important that they remain, to a large extent, themselves.'
One of the people experiencing the consequences of treatment is Paula Piteri. She was 38 years old when she discovered in 2020 that a nodule in her lung was cancer. At the time, she had just become a mother and led a healthy lifestyle with no history of smoking. The discovery was made during a routine check-up. Initially, Paula did not undergo tumor genetic sequencing. She underwent surgery to remove the lesion and thought she had gotten rid of the disease. However, in 2025, she was diagnosed with a new diagnosis: the cancer had returned. 'It was a shock; I am a mother of three children, and this could completely change my life,' she said. Currently, Paula is taking lorlatinibe provided by her health plan. The drug is covered by supplementary health insurance for indications specified by the rules of the National Agency for Supplementary Health Care (ANS).
'It is very good to have perspective, to know that I have a life to live. I want to be part of this and live for many more years,' she stated.
Despite the promising results, access to lorlatinibe remains a problem in Brazil. Before starting treatment, the patient must determine whether the tumor has the ALK genetic mutation. This requires molecular tests that are not always available in the public network or easily accessible through health plans.
For Gustavo Schwartzman, there is a difficulty in ensuring that diagnosis and treatment go hand in hand. He summarized: 'There is no point in doing a test in a system where the drug will not be available. And there is no point in having the drug if the patient could not receive the correct diagnosis.'
Cost is also a barrier. According to the drug price table, one package of 30 tablets can cost around 37 thousand reais. With continuous treatment for seven years, the cost will exceed 3.1 million reais per patient, excluding possible adjustments or discounts.
The inclusion of lorlatinibe in the National Health System (SUS) was considered by the Commission for National Inclusion of Technologies in SUS (Conitec). However, in May 2025, the Ministry of Health published a decision contradicting the provision of the drug to patients with advanced non-small cell lung cancer with the ALK mutation at locally advanced or metastatic stage in first-line treatment. This decision also rejected the inclusion of alectinibe, approving brigatinibe for this indication. The commission's justification related to the cost-benefit ratio of the evaluated therapies. According to the report, the presented values did not meet the criteria for economic efficiency considered appropriate for SUS. As a result, patients needing lorlatinibe depend on coverage by health plans, private purchase, or court rulings to access treatment through the public network.
