Pfizer's Lorlatinib (Lorbrena) Receives FDA Approval for First-Line Treatment of ALK-Positive Metastatic Non-Small Cell Lung Cancer

Source: Jike Pharmaceutical News

On March 3, Pfizer announced that the U.S. Food and Drug Administration (FDA) had approved its supplemental New Drug Application (sNDA) for Lorbrena (lorlatinib), expanding the indication to include first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Lorbrena was previously granted accelerated approval in the United States in 2018 for patients with ALK-positive metastatic NSCLC whose disease had progressed after treatment with certain ALK inhibitors. This application was approved under the FDA’s Real-Time Oncology Review (RTOR) pilot program. The approval of this first-line indication also converts the 2018 accelerated approval into full approval.

The expanded indication for Lorbrena is based on the results of the pivotal Phase 3 CROWN trial. Assessment by blinded independent central review (BICR) demonstrated a 72% reduction in the risk of progression or death with Lorbrena compared with crizotinib in previously untreated patients (HR=0.28; 95% CI: 0.19–0.41; p<0.0001). Central nervous system (CNS) involvement was assessed in all patients in the trial. Based on baseline brain imaging, 17 patients in the Lorbrena group and 13 patients in the crizotinib group had measurable brain metastases. Exploratory analyses showed that, among these patients, the intracranial objective response rate (IC-ORR) assessed by BICR was 82% (95% CI: 57–96) in the Lorbrena group versus 23% (95% CI: 5–54) in the crizotinib group. The duration of intracranial response (IC-DOR) was 12 months or longer in 79% (n=11) of patients in the Lorbrena group and in 0% of patients in the crizotinib group. Detailed results of the CROWN study were published in the New England Journal of Medicine in November 2020.

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80–85% of all lung cancer cases, and ALK-positive tumors occur in about 3–5% of NSCLC cases. In 2020, an estimated 228,820 new cases of lung cancer were diagnosed in the United States. Up to 40% of patients with ALK-positive metastatic NSCLC present with brain metastases at initial diagnosis. Although many patients with ALK-positive metastatic NSCLC initially respond to tyrosine kinase inhibitor (TKI) therapy, their tumors typically progress eventually. Moreover, treatment options are very limited for patients whose disease progresses despite prior treatment with second-generation ALK TKIs.

Lorbrena is a third-generation ALK tyrosine kinase inhibitor (TKI) specifically designed to inhibit the most common tumor mutations (which lead to resistance to current drugs) and to address brain metastases (a common site of disease progression in ALK-positive NSCLC). Lorbrena has demonstrated high activity in preclinical lung cancer models harboring ALK gene rearrangements.

Note: The original text has been abridged.

Note: This article aims to introduce advances in pharmaceutical and health research and does not constitute recommendations for treatment regimens. For guidance on treatment plans, please consult a reputable hospital.

References:

[1] U.S. FDA EXPANDS APPROVAL OF PFIZER’S LORBRENA® AS FIRST-LINE TREATMENT FOR ALK-POSITIVE METASTATIC LUNG CANCER. Retrieved 2021-03-04, from https://www.pfizer.com/news/press-release/press-release-detail/us-fda-expands-approval-pfizers-lorbrenar-first-line

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