The FDA on Friday to protect bone barrow function and reduce the risk of chemotherapy-induced severe neutropenia in small-cell lung cancer (SCLC) patients.
Trilaciclib, a cyclin-dependent kinase (CDK)4/6 inhibitor, is intended for SCLC patients with extensive-stage disease, prior to receipt of chemotherapy. While several other CDK4/6 inhibitors are approved as treatments for breast cancer, this is the first indication for the class as a so-called myeloprotective agent.
"For patients with extensive-stage small cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan," Albert Deisseroth, MD, PhD, of the Division of Non-Malignant Hematology at the FDA's Center for Drug Evaluation and Research, said in a statement. "Today's approval of Cosela will give patients a treatment option that can reduce the occurrence of a common, harmful side effect of chemotherapy."
Approval was based on pooled findings from three randomized, placebo-controlled trials involving 245 patients with extensive-stage SCLC. In results of the studies presented at the 2020 virtual North America Conference on Lung Cancer, 11.4% of those receiving trilaciclib prior to chemotherapy experienced severe neutropenia over the first four treatment cycles versus 52.9% of those assigned placebo (P<0.0001). Average duration of severe neutropenia was 0 versus 4 days, respectively.
"Chemotherapy-induced myelosuppression may lead to increased risks of infection, severe anemia, and/or bleeding," said Jeffrey Crawford, MD, of Duke Cancer Institute in Durham, North Carolina, in a G1 Therapeutics. "To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed."
In the pooled trial data, granulocyte colony stimulating factor (G-CSF) for supportive care was less frequently needed in patients who received trilaciclib (28.5% vs 56.3% with placebo), as were erythropoiesis-stimulating agents (3.3% vs 11.8%).
Common adverse events (AEs) with trilaciclib included fatigue, headache, hypocalcemia, hypokalemia, hypophosphatemia, increased aspartate aminotransferase, and pneumonia. Serious AEs occurred in 30% of patients, with hemorrhage, respiratory failure, and thrombosis being the most common.
In their approval announcement, FDA warned of the risk for acute drug embryo-fetal toxicity, hypersensitivity, injection site reactions, and interstitial lung disease/pneumonitis.