The approval of trilaciclib was based on results from a pooled analysis of intent-to-treat datasets from 3 studies of patients with extensive-stage small cell lung cancer in which patients received standard chemotherapy plus either trilaciclib or placebo.
The FDA has granted approval to the first-in-class agent trilaciclib (Cosela) for the treatment of patients with extensive-stage small cell lung cancer (SCLC) to reduce chemotherapy-induced bone marrow suppression, announced the drugs developer G1 Therapeutics.1
“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, supervisory medical officer in the Division of Non-Malignant Hematology in the FDA's Center for Drug Evaluation and Research, said in a press release. “Today’s approval of [trilaciclib] will give patients a treatment option that can reduce the occurrence of a common, harmful side effect of chemotherapy.”
The approval was based on results from a pooled analysis of intent-to-treat datasets from 3 studies (NCT02499770; NCT03041311; NCT02514447) of patients with extensive-stage SCLC (ES-SCLC) in which patients received standard chemotherapy plus either trilaciclib or placebo. Findings from the pooled analysis were presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.2
In total, 123 patients who were treated with trilaciclib and 119 who were treated with placebo were included. Between the 2 groups, the pooled dataset indicated that median overall survival (OS; 10.6 months [95% CI, 9.1-11.7] vs 10.6 months [95% CI; 7.9-12.8]) and progression-free survival (5.3 months [95% CI, 4.6-6.1] vs 5.0 months [95% CI, 4.4-5.5]) were comparable between the 2 patient groups.
Ultimately though, investigators found that adding trilaciclib resulted in decreased myelosuppression and the need for supportive care interventions in this patient population. Additionally, fewer patients treated with trilaciclib had grade 3/4 hematologic events, with 54 (44.3%) of those experiencing an event versus 91 (77.1%) with placebo.
Of patients who continued treatment after cycle 1, 11 patients (9.2%) in the trilaciclib arm had 1 or more chemotherapy dose reductions compared with 36 patients (30.8%) with placebo.
Trilaciclib is designed to preserve bone marrow and immune system function during chemotherapy, thus improving patient outcomes.3 Pending approval, trilaciclib was made available to patients with SCLC in the United States who were unable to enter clinical trials and for whom there were no appropriate alternative treatments, pursuant to the FDA’s expanded access program (EAP).
In 2019, trilaciclib received breakthrough therapy designation from the FDA, and, in June 2020, G1 Therapeutics submitted a new drug application which received priority review from the FDA in August 2020.
Trilaciclib is also being evaluated in women with metastatic triple-negative breast cancer. Final data from a randomized phase 2 trial (NCT02978716) demonstrated that trilaciclib significantly improved OS for patients treated with trilaciclib in combination with a chemotherapy regimen of gemcitabine/carboplatin (GC) compared with GC alone.4 These data were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS).5
Additionally, trilaciclib is being evaluated as a neoadjuvant treatment for patients with locally advanced breast cancer as part of the I-SPY 2 trial (NCT01042379). Trilaciclib will be evaluated across all high-risk, early-stage breast cancer subtypes and all study participants will receive standard neoadjuvant treatment, including chemotherapy prior to surgical resection of breast tissue. Patients in 2 arms of the study will also receive a PD-1 inhibitor in combination with paclitaxel prior to surgery.
Lastly, the phase 3 PRESERVE trial (NCT04607668) of trilaciclib for patients with metastatic colorectal cancer is currently enrolling. This trial is evaluating the myelopreservation and survival benefits of trilaciclib in combination with chemotherapy, as well as safety and tolerability.
1. FDA approves drug to reduce bone marrow suppression caused by chemotherapy. News release. February 12, 2021. Accessed February 12, 2021. https://prnmedia.prnewswire.com/news-releases/fda-approves-drug-to-reduce-bone-marrow-suppression-caused-by-chemotherapy-301227821.html
2. Weiss J, Goldschmidt J, Zoran A, et al. Myelopreservation and reduced use of supportive care with trilaciclib in patients with small cell lung cancer. J Clin Oncol. 2020(suppl 38; abstr 12096). doi:10.1200/JCO.2020.38.15_suppl.12096
3. G1 Therapeutics announces acceptance and priority review of NDA for trilaciclib for patients with small cell lung cancer. News release. G1 Therapeutics. Published August 17, 2020. Accessed January 20, 2021. http://investor.g1therapeutics.com/news-releases/news-release-details/g1-therapeutics-announces-acceptance-and-priority-review-nda
4. G1 Therapeutics. Trilaciclib. G1 Therapeutics website. Published 2021. Accessed January 20, 2021. https://www.g1therapeutics.com/pipeline/trilaciclib/
5. O’Shaughnessy J, Wright GS, Thummala AR, et al. Trilaciclib improves overall survival when given with gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer: final analysis of a randomized phase 2 trial. Presented at the 2020 San Antonio Breast Cancer Symposium. December 8-11, 2020. Poster #PD1-06.