FDA Approves Trilaciclib to Reduce Chemo-Induced Bone Marrow Suppression in ES-SCLC

FDA

The FDA has approved trilaciclib (Cosela) to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving certain types of chemotherapy for extensive-stage small cell lung cancer (ES-SCLC).¹

“For patients with ES-SCLC, 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, stated 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.”

Trilaciclib was evaluated in 3 double-blind, placebo-controlled phase 2 trials in adult patients with ES-SCLC: G1T28-02 (NCT02499770), G1T28-05 (NCT03041311), and G1T28-03 (NCT02514447).^2-4 In an analysis presented during the 2020 ASCO Virtual Scientific Program, investigators examined the pooled data from these trials to characterize the myelopreservation effects of the CDK4/6 inhibitor.

G1T28-02 evaluated the clinical benefit of trilaciclib in preserving the bone marrow and the immune system while augmenting the antitumor activity of chemotherapy when given before carboplatin and etoposide in the first-line treatment of patients with newly diagnosed disease. In this trial, patients were administered either trilaciclib or placebo on days 1 through 3 of each 21-day cycle.

In G1T28-05, investigators evaluated the potential benefit of the CDK4/6 inhibitor in preserving bone marrow and the immune system while encouraging antitumor efficacy when given with carboplatin, etoposide, and atezolizumab (Tecentriq) in the frontline treatment of patients with newly diagnosed disease. Here, patients received either trilaciclib or placebo on days 1 through 3 of each 21-day treatment cycle for up to 4 cycles as part of the induction phase; this was followed by atezolizumab, given every 21 days, as part of the maintenance phase.

In G1T28-03, investigators set out to understand the benefit of trilaciclib in preserving bone marrow and the immune system while boosting the antitumor activity of chemotherapy when administered prior to topotecan in patients with ES-SCLC who had received previous treatment. For this research, patients were given either trilaciclib or placebo on days 1 through 5 of each 21-day cycle of topotecan.

For the analysis, investigators examined trilaciclib with regard to myelopreservation and antitumor activity. The primary myelopreservation end points included duration of severe neutropenia (DSN), which was defined as grade 4 in cycle 1 and occurrence of severe neutropenia (SN) across the treatment period. Secondary myelopreservation end points were examined through hematopoietic lineage, including neutrophils, red blood cells, and platelets.

Additionally, to examine antitumor activity, investigators looked at objective response, progression-free survival (PFS), and overall survival (OS). Safety was also assessed in all study participants who received 1 or more doses of trilaciclib.

Data from a total of 119 patients who had received placebo prior to chemotherapy and 123 patients who received trilaciclib prior to chemotherapy were examined for the analysis. Baseline characteristics of patients proved to be comparable between the 2 groups of patients. Across the groups, most of the participants were Caucasian (97.6% and 92.4%, respectively), had an ECOG performance status of 0 or 1 (87.8% and 89.9%), and did not have brain metastases (77.2% and 75.6%).

Results demonstrated that tumor responses were comparable between the treatment groups; 49.1% of patients who received trilaciclib prior to chemotherapy experienced a response versus 51.8% of those who were given placebo (P = .7879). PFS and OS also proved to be comparable between the groups. For those in the experimental arm, the PFS was 5.3 months (95% CI, 4.6-6.1) compared with 5.0 months for those in the placebo arm (HR, 0.80; 95% CI, 0.61-1.06; P = .1404). Additionally, the median OS was 10.6 months in both groups (HR, 1.00; 95% CI, 0.75-1.35; P = .8136).

Trilaciclib, when given before chemotherapy, was found to lead to a significant decrease in most measures of multilineage chemotherapy-induced myelosuppression and the need for supportive care interventions. Moreover, the primary end points of DSN in cycle 1 and the occurrence of SN were found to be significantly decreased in those who received trilaciclib versus those given placebo; the mean DSN with trilaciclib and placebo was 0 compared with 4 days, respectively (P <.0001).

Of the patients who continued treatment after cycle 1, 8.9% of those in the trilaciclib group required 1 or more dose reductions of chemotherapy versus 30.3% of those in the placebo group (event rate per 100 cycles: 2.8 vs 9.3, respectively). Additionally, fewer patients who received trilaciclib reported serious toxicities compared with those who had received placebo, at 6.5% versus 10.1%, respectively; also, fewer patients needed treatment with intravenous antibiotics, at 19.5% versus 23.5%, respectively.

Regarding safety, treatment-emergent AEs (TEAEs) were experienced by 96.6% of those who received placebo compared with 94.3% of those who received trilaciclib. The most frequently experienced TEAEs comprised neutropenia, anemia, thrombocytopenia, nausea, and fatigue. Moreover, significantly fewer patients who received the CDK4/6 inhibitor prior to chemotherapy reported high-grade hematologic toxicities compared with those who were given placebo.

References

1. FDA approves drug to reduce bone marrow suppression caused by chemotherapy. FDA. News release. February 12, 2021. Accessed February 12, 2021. http://bit.ly/379OETw.
2. Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase 1b/randomized phase II trial. Ann Oncol. 2019;30 (suppl 5):1613-1621. doi:10.1093/annonc/mdz278
3. Daniel D, Kuchava V, Bondarenko I, et al. Trilaciclib decreases myelosuppression in extensive-stage small cell lung cancer (ES-SCLC) patients receiving first-line chemotherapy plus atezolizumab. Ann Oncol. 2019;30(suppl 5):v713. doi:10.1093/annonc/mdz264.006
4. Hart LL, Andric ZG, Hussein MA, et al. Effect of trilaciclib, a CDK4/6 inhibitor, on myelosuppression in patients with previously treated extensive-stage small cell lung cancer receiving topotecan. J Clin Oncol. 2019;37(suppl 15):8505. doi:10.1200/JCO.2019.37.15_suppl.8505