Seven year analysis from Pfizer’s LORBRENA CROWN trial delivers the longest progression free survival reported so far in advanced non small cell lung cancer

Patients had a 55% likelihood of remaining alive and free from disease progression at seven years, and median progression free survival had not been reached with LORBRENA. The updated follow up analysis cements LORBRENA as a preferred standard of care, building on previously reported five year results.

Pfizer has shared unprecedented seven year follow up results from the Phase 3 CROWN trial, which evaluated LORBRENA (lorlatinib, a third generation ALK inhibitor, available in Europe under the brand name LORVIQUA) against XALKORI (crizotinib) in people with previously untreated, anaplastic lymphoma kinase (ALK) positive advanced or metastatic non small cell lung cancer (NSCLC).

At the seven year mark, patients treated with LORBRENA had a 55% likelihood of remaining alive and progression free (95% confidence interval 46 to 63), compared with 3% (95% confidence interval 1 to 8) in the XALKORI arm. An updated analysis at seven years of median follow up also showed that investigator assessed median progression free survival had not been reached with LORBRENA, with an estimated hazard ratio of 0.19 (95% confidence interval 0.13 to 0.26). This represents an 81% reduction in the risk of disease progression or death versus XALKORI. The full results will be presented in an oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #8502) and published simultaneously in Annals of Oncology.

“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.”

Lung cancer remains the leading cause of cancer related deaths worldwide, with close to 230,000 new cases expected in the US in 2026. NSCLC accounts for around 75 to 80% of all lung cancers, and ALK positive tumours arise in about 3 to 5% of NSCLC cases. Roughly 25 to 40% of people with ALK positive advanced NSCLC may develop brain metastases within two years of initial diagnosis, which are linked to poorer survival outcomes and can have a profound impact on cognitive function and quality of life.

LORBRENA was specifically designed and developed by Pfizer to inhibit tumour mutations that drive resistance to other ALK inhibitors, and to cross the blood brain barrier. The seven year follow up data showed that LORBRENA both prevented and controlled brain metastases, delivering a 94% reduction in the risk of developing intracranial progression (hazard ratio 0.06; 95% confidence interval 0.03 to 0.12), with no new intracranial progression events recorded after the first 30 months. Median time to intracranial progression had not been reached (95% confidence interval not reached to not reached) with LORBRENA, compared with 16.4 months (12.7 to 21.9) with XALKORI. At the time of analysis, 44% of patients in the CROWN trial were still receiving LORBRENA, versus 3% of patients on XALKORI.

“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, 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. “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.”

“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, M.D., 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.”

The safety profiles of both LORBRENA and XALKORI were consistent with previous findings, and no new safety signals were observed. In this analysis, the most frequent (occurring in 20% or more of patients) adverse events of interest reported with LORBRENA included edema, weight gain, peripheral neuropathy, cognitive effects, mood effects, diarrhoea, dyspnoea, arthralgia, hypertension, headache, cough, pyrexia, hypercholesterolemia, and hypertriglyceridemia. All cause grade 3 or 4 adverse events occurred in 77% of patients on LORBRENA and in 57% of those on XALKORI. Treatment related adverse events led to permanent treatment discontinuation in 5% and 6% of patients in the LORBRENA and XALKORI arms, respectively. No new permanent discontinuations driven by treatment related adverse events occurred after the first 26 months with LORBRENA.

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non-small cell lung cancer, Pfizer, Pfizer's LORBRENA CROWN trial