Data indicate that 55% of patients with NSCLC (non-small cell) lung cancer remain alive and without disease progression after 7 years of treatment with Lorbrena, a Pfizer drug to inhibit tumor mutations associated with resistance to other ALK inhibitors.
The drug was tested in comparison with Xalkori, which had 3% of patients alive without their cancer progressing.
Furthermore, an updated analysis with the same analysis period showed that the median progression-free survival was not reached with Lorbrena with an estimated risk ratio of 0.19 (95% CI: 0.13-0.26), a factor that represents an 81% reduction in the risk of disease progression or death compared to the other medicine.
The complete results of the study were presented at the (Annual Congress of the American Society of Clinical Oncology), based in Chicago, in the United States (USA) and published simultaneously in the journal Annals of Oncology, in May.
Pfizer Global Oncology Clinical Lead Jeff Legos reports that “although it is not possible to draw definitive conclusions across studies, this appears to be the longest median progression-free survival time ever observed in lung cancer.”
In addition, the research also concluded that Lorbrena prevented and controlled brain metastases by 94% in the risk of intracancer (IC) prevention (risk ratio [HR] 0.06; 95% CI: 0.03-0.12) after the first 30 months.
The median time to progression in the central nervous system was not reached with Lorbrena (95% CI: NA-NA) and was 16.4 months (95% CI: 12.7-21.9) with Xalkori. At the time of analysis, 44% of patients in the CROWN study remained on Lorbrena, compared to 3% of patients on Xalkori.
The profiles of both drugs were consistent with previous findings, with no new safety signals. Adverse events frequently reported by patients treated with Lorbrena included swelling, weight gain, peripheral neuropathy, cognitive effects, mood changes, diarrhea, shortness of breath or difficulty breathing, joint pain, hypertension, headache, cough, fever, hypercholesterolemia, and hypertriglyceridemia.
Grade three and four events among all these causes occurred in 77% of patients with Lorbrena and 57% of those using Xalkori.
Other side effects led to permanent discontinuation of 5% of Lorbrena patients and 6% of Xalkori patients. There were no new treatments discontinued due to treatment side effects after the first 26 months with Lorbrena.
The study
CROWN is a Phase 3, randomized, open-label, two-pronged, parallel study. In them, 296 people with untreated advanced ALK-positive NSCLC were randomized to receive monotherapy treatment with Lorbrena (n=149) or Xalkori (n= 147).
The study endpoint was progression-free time based on BICR (Blinded Independent Central Review), with a secondary endpoint of overall progression-free time, which is ongoing follow-up.
O Lorbena
Approved in Brazil by Anvisa (National Health Surveillance Agency) in 2020, initially for patients who did not respond to other treatments for ALK-positive advanced NSCLC. Subsequently, in 2021, receiving registration for first-line treatment in the country and, in 2022, incorporated into the list of mandatory coverage in health plans.
The medical director of Pfizer Brazil, Adriana Ribeiro, points out that “until the beginning of the last decade, there were limited options for patients with alterations in the ALK gene, but the advancement of ALK enabled the development of targeted therapies that act directly on tumor cells.”
Lung cancer
It is the leading cause of cancer deaths in the world. According to INCA (National Cancer Institute), it is estimated that there are around 32 thousand new cases per year in Brazil, proving to be one of the types that causes the most deaths from cancer in the country.
Non-small cell lung cancer (NSCLC) represents approximately 75% to 80% of lung cancers, 2,4 and ALK-positive tumors occur in approximately 3% to 5% of NSCLC cases. 4 Approximately 25% to 40% of people with advanced, ALK-positive NSCLC may develop metastases within two years of initial diagnosis, a condition associated with lower survival rates and which can profoundly affect cognitive function and quality of life.
