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FDA Approves Lorbrena for ALK+ NSCLC

The U.S. Food and Drug Administration (FDA) has granted an accelerated approval for Lorbrena (lorlatinib) in the treatment for patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on 1 or more ALK tyrosine kinase inhibitors (TKIs). 1 These medications include:

  • Xalkori (crizotinib) and at least one other ALK inhibitor for metastatic disease
  • Alecensa (alectinib) as the first ALK inhibitor therapy for metastatic disease
  • Zykadia (ceritinib) as the first ALK inhibitor therapy for metastatic disease

“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. Yet almost all patients still relapse due to drug resistance…” Alice T. Shaw, MD, PhD, Professor of Medicine at Harvard Medical School, and Director of the Center for Thoracic Cancers at Massachusetts General Hospital, said in the press release.2

Promising clinical trial results

The approval for Lorbrena came after positive results from a nonrandomized, dose-ranging, multicohort, multicenter phase II study that included a subgroup of 215 patients with ALK-positive stage IV NSCLC who previously were treated with other ALK-targeted drugs. Patients received 100 mg of Lorbrena once daily. The overall response rate for those ALK-positive patients was 48%, with a complete response rate of 4% and a partial response rate of 44%. 69% of patients had a history of brain metastases and the intracranial response rate was 60%. The median response duration was 12.5 months.

“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,” noted Dr. Shaw.2

The most common adverse reactions included edema (swelling), peripheral neuropathy, cognitive effects, dyspnea (trouble breathing), fatigue, weight gain, arthralgia (joint pain), mood effects, and diarrhea. Serious adverse reactions occurred in 32% of those patients participating. The most frequent reactions reported were pneumonia (3.4%), dyspnea (2.7%), pyrexia (fever) (2%), mental status changes (1.4%), and respiratory failure (1.4%).

An important milestone

This approval marks a critical step forward in lung cancer research development, especially for those with the ALK-mutation. Mace Rothenberg, chief development officer of oncology, Pfizer Global Product Development, commented “Lorbrena’s approval is an important milestone for patients, having demonstrated marked activity in a study that included a broad range of individuals with ALK-positive non-small cell lung cancer. This includes patients who were heavily pretreated and facing limited options after receiving first — and second — generation ALK tyrosine kinase inhibitors.”2

  1. U.S. Food and Drug Administration. FDA approves lorlatinib for second- or third-line treatment of ALK-positive metastatic NSCLC. Accessed online November 5, 2018.
  2. Pfizer. U.S. FDA Approves Lorbrena® (Lorlatinib) For Previously-treated ALK-positive Metastatic NSCLC. Accessed online November 5, 2018.