FDA Gives Pfizer’s Lorbrena Thumbs-up for ALK Mutation Lung Cancer

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The U.S. Food and Drug Administration (FDA) approved Pfizer’s Lorbrena (lorlatinib) for ALK-positive metastatic non-small cell lung cancer (NSCLC) in patients whose disease hasn’t progressed on crizotinib and at least one other ALK inhibitor or for patients whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor.

That’s quite a mouthful, but the agency approved the drug for lung cancer patients with a specific gene mutation—ALK—who had previously been treated. Lorbrena is currently approved in Japan for ALK fusion gene-positive unresectable advanced and/or recurrent NSCLC with resistance or intolerance to ALK tyrosine kinase inhibitors.

This resistant form of cancer is particularly aggressive. The first TKI approved was Pfizer’s Xalkori (crizotinib). It was approved by the FDA in 2011. Other TKI’s include Novartis Zykadia (ceritinib) and Roches Alecensa (alectinib).

A Phase I/II clinical trialed showed Lorbrena’s overall response rate (ORR) was 48 percent. Of those in the trial, 57 percent had previous treatment with one or more TKIs.

“Over the years, Pfizer has transformed research, management and treatment for patients with ALK-positive non-small cell lung cancer,” stated Andy Schmeltz, Global President, Pfizer Oncology. “Building upon our extensive understanding of tumor complexity and treatment resistance, Lorbrena was discovered by Pfizer scientists and developed specifically to inhibit tumor mutations that may drive resistance to other ALK tyrosine kinase inhibitors.”

The company notes that, although many NSCLC patients who test positive for ALK respond to initial TKI therapy, they generally experience tumor progression. The options for patients who progress after treatment with alectinib, brigatinib and ceritinib are limited, so Lorbrena represents a new option for those patients.

“The last decade has witnessed dramatic improvements in the treatment of metastatic ALK-positive non-small cell lung cancer due to earlier generation ALK biomarker-driven therapies,” stated Alice T. Shaw, professor of Medicine at Harvard Medical School and director of the Center for Thoracic Cancers at Massachusetts General Hospital. “Yet almost all patients still relapse due to drug resistance, with a large proportion of patients developing new or worsening brain metastases.”

Shaw went on to say, “In a clinical study which included patients with or without brain metastases, Lorbrena demonstrated clinical activity in patients with metastatic ALK-positive non-small cell lung cancer who had failed other ALK biomarker-driven therapies.”

The thumbs-up was given by the FDA under an accelerated approval based on tumor response rate and duration of response. Although approved, its continued approval will be based on verification and clinical benefit shown in a confirmatory clinical trial.

Lung cancer is one of the deadliest cancers, and it is the leading cause of cancer deaths globally. NSCLC makes up about 85 percent of lung cancers and is difficult to treat, especially in the metastatic setting. About 75 percent of NSCLC patients are diagnosed late with metastatic or advanced cancer, at which point the five-year survival rate is about five percent.

ALK mutations drive the development of lung cancer in some cases. Studies have indicated about three to five percent of NSCLC tumors are ALK-positive.

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