Global pharma giant Pfizer has reported that its LORBRENA therapy produced landmark seven-year survival results in a trial involving advanced lung cancer patients.
In Phase 3 CROWN trial, the company says, more than half of patients treated with LORBRENA remained alive without disease progression seven years after starting therapy for metastatic non-small cell lung cancer (NSCLC).
The findings mark one of the longest progression-free survival outcomes ever reported in advanced lung cancer.
Seven years into the study, 55% of patients receiving LORBRENA (lorlatinib) remained alive and progression-free, compared with just 3% of patients treated with XALKORI (crizotinib).
Median progression-free survival has still not been reached in the LORBRENA arm, while the treatment reduced the risk of disease progression or death by 81% compared with XALKORI.
“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 seven 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,” said Jeff Legos, Chief Oncology Officer, Pfizer.
“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.”
The results are particularly significant for patients with ALK-positive NSCLC, a subtype that accounts for roughly 3% to 5% of all non-small cell lung cancer cases. The disease often spreads to the brain, creating additional treatment challenges and worsening outcomes.
Designed to overcome resistance to earlier ALK-targeted therapies and penetrate the blood-brain barrier, LORBRENA demonstrated strong and lasting protection against brain metastases.
The drug reduced the risk of intracranial disease progression by 94%, and researchers reported no new brain progression events after the first 30 months of treatment.
The median time to intracranial progression was not reached among patients receiving LORBRENA, compared with 16.4 months for those treated with XALKORI. At the time of analysis, 44% of patients remained on LORBRENA therapy, versus just 3% in the XALKORI group.
“These seven-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,” said Tony Shu-Kam Mok, Principal Investigator of the CROWN trial.
“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.”
Patient advocates also hailed the findings as evidence that long-term disease control is becoming an achievable goal for many people living with ALK-positive lung cancer.
“Behind every clinical trial is a person continuing to live their life—raising children, pursuing careers, making memories—without their cancer progressing,” said Kenneth Culver, Director of Research and Clinical Affairs at the non-profit organization ALK Positive.
“These seven-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.”
Safety findings remained consistent with earlier analyses, with no new safety signals identified during the extended follow-up period.
While severe adverse events were reported more frequently among patients receiving LORBRENA than XALKORI, treatment discontinuation rates due to side effects remained low and comparable between both groups.
Lung cancer remains the world's leading cause of cancer-related deaths.
