Cosela Approved for Protection Against Myelosuppression From SCLC Treatment

The cyclin-dependent kinase 4/6 inhibitor trilaciclib (Cosela) is the first in its class to receive FDA approval as a protective agent against bone marrow loss from treatment for small cell lung cancer (SCLC).

The FDA approved trilaciclib (Cosela; G1 Therapeutics) to be used as a protective agent against bone marrow loss among adults before chemotherapy regimens that contain a platinum agent/etoposide or topotecan for extensive-stage small cell lung cancer. This is the first and only such approval for a cyclin-dependent kinase 4/6 inhibitor.

Bone marrow loss and myelosuppression are well-documented adverse effects (AEs) of chemotherapy, leaving the immune system without some of its most potent fighters: red blood cells, which contain hemoglobin; white blood cells, which help to fight infection; and platelets, which assist in clotting. These losses, in turn, can cause fatigue and increase risks of infection, bleeding, anemia, and thrombocytopenia.

Previous treatments that address bone marrow injury have only attempted to remedy it after the fact. “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,” stated Jeffrey Crawford, MD, Geller Professor for Research in Cancer in the Department of Medicine and Duke Cancer Institute, in G1 Therapeutics’ news release. “By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.”

G1 Therapeutics’ application was backed by data from 3 double-blind, placebo-controlled studies of 245 patients randomized to intravenous (IV) trilaciclib or placebo, with dual primary outcomes of severe neutropenia and its length during the first chemotherapy cycle. The effectiveness of trilaciclib plus carboplatin/etoposide (with or without atezolizumab) or topotecan was evaluated in these trials. Severe neutropenia was a less likely outcome, and lasted for a shorter time among those for whom it did occur, following treatment with trilaciclib. These findings were deemed clinically meaningful and statistically significant.

Most common AEs (≥10%) of the treatment are fatigue, headache, high aspartate aminotransferase levels, pneumonia, and low calcium, potassium, and phosphate levels. Injection-site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity are also possible.

Serious AEs that occurred (>3%) were respiratory failure, hemorrhage, and thrombosis; fatal AEs were seen in 5% (pneumonia, 2%; respiratory failure, 2%; acute respiratory failure, <1%; hemoptysis, <1%; and cerebrovascular accident, <1%); and 9% permanently discontinued the preventive measure for reasons that included asthenia, ischemic stroke, and myositis.

“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,” said Albert Deisseroth, MD, PhD, supervisory medical officer in the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research, in a statement from the FDA. “Cosela will give patients a treatment option that can reduce the occurrence of a common, harmful side effect of chemotherapy.”

Cosela received a Breakthrough Therapy designation in 2019 and a Priority Review in 2020; a postapproval clinical trial is currently scheduled for 2022.

The treatment is administered as a 30-minute IV infusion within 4 hours of the start of chemotherapy.

Reference

FDA approves G1 Therapeutics’ Cosela (trilaciclib): the first and only myeloprotection therapy to decrease the incidence of chemotherapy-induced myelosuppression. News release. G1 Therapeutics. February 12, 2021. Accessed February 17, 2021. http://investor.g1therapeutics.com/news-releases/news-release-details/fda-approves-g1-therapeutics-coselatm-trilaciclib-first-and-only