Pfizer has announced unprecedented 7-year follow-up results from the phase 3 CROWN trial evaluating LORBRENA (lorlatinib, a third-generation ALK inhibitor, available in Europe under the brand name LORVIQUA) versus XALKORI (crizotinib) in people with previously untreated, Anaplastic Lymphoma Kinase (ALK)-positive advanced or metastatic Non-Small Cell Lung Cancer (NSCLC).

At 7 years, patients treated with LORBRENA had a 55 percent likelihood of remaining alive without disease progression (95 percent Confidence Interval [CI], 46-63) compared to 3 percent (95 percent CI, 1-8) in the XALKORI treatment arm. Further, an updated analysis at 7 years of median follow-up showed that investigator-assessed median Progression-Free Survival (PFS) had not been reached with LORBRENA, with an estimated Hazard Ratio (HR) of 0.19 (95 percent CI, 0.13-0.26), representing an 81 percent reduction in the risk of disease progression or death compared to XALKORI.

Jeff Legos, Chief Oncology Officer, Pfizer, said, “The updated results from the CROWN trial show unprecedented long-term clinical benefit, with estimates indicating the majority of patients treated with LORBRENA remained alive and progression-free at 7 years. While definitive conclusions cannot be drawn across studies, this appears to represent the longest observed Progression-Free Survival reported to date in metastatic or advanced lung cancer. These findings further showcase Pfizer’s world-class discovery expertise and our commitment to developing breakthroughs that help improve care for people with advanced NSCLC.”

Lung cancer is the leading cause of cancer-related deaths worldwide, and nearly 230,000 new cases are expected in the US in 2026. NSCLC accounts for approximately 75-80 percent of lung cancers, with ALK-positive tumors occurring in about 3-5 percent of NSCLC cases. Approximately, 25-40 percent of people with ALK-positive advanced NSCLC may develop brain metastases within 2 years from initial diagnosis, which are associated with poorer survival and can profoundly affect cognitive function and quality of life.

LORBRENA was specifically designed and developed by Pfizer to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood-brain barrier. Results from this 7-year follow-up showed that LORBRENA prevented and controlled brain metastases, with a 94 percent reduction in the risk of developing intracranial (IC) progression (HR, 0.06; 95 percent CI, 0.03-0.12) and no new IC progression events occurring after the first 30 months. The median time to IC progression was not reached (95 percent CI, NR-NR) with LORBRENA and was 16.4 months (12.7-21.9) with XALKORI. At the time of analysis, 44 percent of patients in the CROWN trial were still receiving LORBRENA compared to 3 percent of patients receiving XALKORI.

Tony Shu-Kam Mok, BBS, Endowed Professor, Li Shu Fan Medical Foundation, Chairman of the Dept. of Clinical Oncology, Chinese University of Hong Kong, and Principal Investigator of the CROWN trial, said, “These 7-year outcomes from the CROWN study are remarkable not only for their durability of tumor response but for what they represent—a fundamental shift in what clinicians and patients might reasonably expect from treatment for advanced-stage NSCLC. Observing this level of long-term benefit with a once-daily oral therapy, both in terms of sustained Progression-Free Survival and prevention of brain metastases, would have been difficult to imagine when we first developed ALK-specific targeted therapy a decade ago and underscores the significance of these results for the lung cancer community.”

The safety profiles of LORBRENA and XALKORI were consistent with previous findings, with no new safety signals observed. In this analysis, the most frequent (≥20 percent) Adverse Events (AEs) of interest reported in patients treated with LORBRENA included edema, weight gain, peripheral neuropathy, cognitive effects, mood effects, diarrhea, dyspnea, arthralgia, hypertension, headache, cough, pyrexia, hypercholesterolemia, and hypertriglyceridemia. All-cause grade 3/4 AEs occurred in 77 percent of patients with LORBRENA and in 57 percent of patients with XALKORI. Treatment-related AEs led to permanent treatment discontinuation in 5 percent and 6 percent of patients in the LORBRENA and XALKORI arms, respectively. No new permanent discontinuations due to treatment-related AEs occurred after the first 26 months with LORBRENA.

Kenneth Culver, MD, Director of Research and Clinical Affairs at the non-profit organisation ALK Positive, said, “Behind every clinical trial is a person continuing to live their life—raising children, pursuing careers, making memories—without their cancer progressing. These 7-year results provide compelling evidence that long-term disease control is possible, and we applaud Pfizer's dedication to advancing treatments that are changing what it means to live with ALK-positive lung cancer.”