Last year, clinicians who treat patients with metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC) saw the approval of 6 new agents. The agents include the first drug approved for patients whose tumors express PD-L1 and 3 that garnered “breakthrough therapy designation,” including 1 that was granted orphan drug status.
In 2015 alectinib (Alecensa, Genentech, Inc.), gefitinib (Iressa, AstraZeneca Pharmaceuticals, LP), necitumumab (Portrazza, Eli Lilly and Company), nivolumab (Opdivo, Bristol-Myers Squibb Company), osimertinib (Tagrisso, AstraZeneca), and pembrolizumab (Keytruda, Merck & Co., Inc.) were all approved by the U.S. Food and Drug Administration (FDA).
These drug approvals illustrate a “growing understanding of underlying molecular pathways,” noted Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. They are also delivering on the promise of personalized medicine: all of the agents are indicated for patients who harbor specific gene mutations, and 3 must be used with FDA-approved companion diagnostic tests.
The FDA approved alectinib on December 11, 2015. The agent, a second-generation, orally active, potent and highly selective inhibitor of anaplastic lymphoma kinase (ALK), is indicated for patients with metastatic ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib. About 5% of patients with NSCLC are ALK-positive. Alectinib received orphan drug designation, breakthrough therapy designation, priority review status, and accelerated approval. The recommended dose is 600 mg orally twice daily with food.1
Gefitinib, approved on July 13, 2015, is a tyrosine kinase inhibitor indicated for patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. The agent was approved concurrently with a labeling expansion of the therascreen® EGFR RGQ PCR Kit, a companion diagnostic test for patient selection. The recommended dose of gefitinib is 250 mg orally once daily with or without food.2