Your Health, We Care
Release date: 2026-01-23 11:39:21 Recommended: 15
On January 28, 2022, Pfizer Inc. announced that the European Commission (EC) had approved the marketing authorization of lorlatinib (LORVIQUA®, LORBRENA®) as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) who have not received prior ALK inhibitor therapy.
Lorlatinib (LORVIQUA®, lorlatinib) is a tyrosine kinase inhibitor (TKI) that has demonstrated high activity in preclinical lung cancer models harboring ALK chromosomal rearrangements. Specifically designed to inhibit tumor mutations that confer resistance to other ALK inhibitors, lorlatinib is capable of crossing the blood-brain barrier and is recognized as a third-generation ALK inhibitor.
Andy Schmeltz, Global President and General Manager of Pfizer Oncology, stated, "For more than a decade, Pfizer has been relentlessly committed to helping transform the lives of patients with advanced biomarker-driven lung cancer. The EC’s approval of lorlatinib as a first-line therapy represents a significant milestone, and we hope this will bring the necessary and meaningful changes for patients across Europe affected by this life-threatening disease."
The approval of lorlatinib (LORVIQUA®, lorlatinib) for first-line use is based on the results of the pivotal Phase 3 CROWN trial, a randomized, open-label, parallel-arm study. A total of 296 previously untreated patients with advanced ALK-positive NSCLC were randomized in a 1:1 ratio to receive either lorlatinib monotherapy (n=149) or crizotinib monotherapy (crizotinib, XALKORI®; n=147).
The primary endpoint of the CROWN trial was progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). Secondary endpoints included overall survival (OS) and BICR-assessed tumor-related metrics, including objective response rate (ORR) and duration of response (DOR).
Trial results showed that lorlatinib (LORVIQUA®, lorlatinib) reduced the risk of disease progression or death by 72% compared with crizotinib. The objective response rate (ORR) was 76% (95% CI, 68–83) with lorlatinib versus 58% (95% CI, 49–66) with crizotinib. Among patients with measurable brain metastases, 82% of those in the lorlatinib arm achieved intracranial response (with 71% achieving complete intracranial response), compared with only 23% in the crizotinib arm.
The safety profile of lorlatinib (LORVIQUA®, lorlatinib) was consistent with that reported in previous studies. Among the 149 patients treated with lorlatinib, the most common adverse events (AEs, ≥20%) included edema, weight gain, peripheral neuropathy, cognitive effects, diarrhea, dyspnea, and hypertriglyceridemia. Severe AEs occurred in 34% of patients receiving lorlatinib; the most frequently reported severe AEs were pneumonia, dyspnea, respiratory failure, cognitive effects, and heatstroke. Fatal AEs were reported in 3.4% of patients treated with lorlatinib, and 6.7% of patients permanently discontinued lorlatinib treatment due to AEs. Detailed results from the CROWN study were published in the New England Journal of Medicine in November 2020.
The EC approval of lorlatinib (LORVIQUA®, lorlatinib) follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) in December 2021. In November 2018, the U.S. Food and Drug Administration (FDA) approved lorlatinib (brand name: LORBRENA) for the treatment of adult patients with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. In 2019, the European Commission granted a conditional marketing authorization for lorlatinib as a monotherapy for adult patients with ALK-positive advanced NSCLC whose disease has progressed after first-line treatment with an ALK tyrosine kinase inhibitor (TKI), or after treatment with crizotinib and at least one other ALK TKI.
