Trilaciclib Added to NCCN Guidelines for SCLC and Hematopoietic Growth Factors

Raj Malik, MD

The National Comprehensive Cancer Network® (NCCN) has added the CDK4/6 inhibitor trilaciclib (Cosela) to its Clinical Practice Guidelines in Oncology for small cell lung cancer as well as for supportive care for hematopoietic growth factors.¹

Previously, in February 2021, the FDA approved trilaciclib for use in adult patients receiving certain types of chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) to reduce the frequency of chemotherapy-induced bone marrow suppression. The regulatory decision followed the agent’s evaluation in 3 double-blind, placebo-controlled phase 2 trials in this patient population, including G1T28-02 (NCT02499770), G1T28-05 (NCT03041311), and G1T28-03 (NCT02514447).

“The inclusion of Cosela in these NCCN guidelines is critical, as they are the standard resource for determining best course of treatment and supportive care for people living with cancer, and as such will enable healthcare providers to make informed decisions when treating patients with small cell lung cancer,” Raj Malik, MD, chief medical officer of G1 Therapeutics, the developer of trilaciclib, said in a press release. “Cosela is an innovative product; it is the first and only proactive multilineage myeloprotection agent for use in extensive-stage small cell lung cancer. We welcome the rapid and simultaneous inclusion in both updated guidelines which reinforces Cosela’s clinical utility and importance to patients.”

Trilaciclib proactively delivers multilineage myeloprotection to patients with ES-SCLC being treated and is often administered intravenously within 4 hours of starting therapy.

In the phase 2 G1T28-02 trial, which examined the safety, efficacy, and pharmacokinetics of trilaciclib in combination with etoposide plus carboplatin for patients with treatment-naive ES-SCLC, the agent showed an improvement in chemotherapy tolerability, which was demonstrated by myelopreservation across multiple hematopoietic lineages.² This resulted fewer dose reductions, an improved safety profile, and no detriment to antitumor activity.

A total 122 patients were enrolled and received trilaciclib or placebo before treatment with etoposide/carboplatin on days 1 through 3 of each therapy cycle. When compared with placebo, trilaciclib demonstrated superior antitumor activity with an overall response rate (ORR) of 66.7% vs 56.8%, respectively (P = .3831). The median progression-free survival (PFS) for trilaciclib was 6.2 months vs 5.0 months for placebo (HR, 0.71; P = .1695), while the median overall survival was 10.9 months for trilaciclib versus 10.6 months for placebo (HR, 0.87; P = .6107).

In terms of safety, grade 3 or higher adverse events were observed in 50% of patients with trilaciclib compared with 83.8% of patients with placebo.

In the phase 2 G1T28-05 trial, which examined trilaciclib prior to chemotherapy and atezolizumab (Tecentriq) in patients with newly diagnosed ES-SCLC, the agent also demonstrated an improved safety profile and health-related quality of life. On this study, 52 patients received trilaciclib prior to treatment with chemotherapy/atezolizumab, and 53 received placebo. The primary endpoints were duration of severe neutropenia, defined as absolute neutrophil count of less than 0.5 × 10⁹ cells/L, as well as occurrence of severe neutropenia during treatment.³

Results showed that trilaciclib led to decreases in duration of severe neutropenia in cycle 1 of treatment at 0 days vs 4 days with placebo (P <.0001), as well as a statistically significant decrease in the recurrence of severe neutropenia at 1.9% vs 49.1% with placebo.

Finally, in the phase 2 G1T28-03 study, which looked at patients with previously treated ES-SCLC receiving topotecan, trilaciclib again decreased rates of chemotherapy-induced myelosuppression, as well as demonstrated improved tolerability with topotecan vs placebo.⁴ On this study, 91 patients were randomized to receive trilaciclib at a dose of 240 mg/m2 plus topotecan at a dose of 0.75 mg/m², trilaciclib at a dose of 240 mg/m² plus topotecan at a dose of 1.5 mg/m², or placebo plus topotecan at a dose of 1.5 mg/m² intravenously on days 1 through 5 of 21-day cycles.

Results showed that patients receiving trilaciclib plus the 1.5 mg/m² dose of topotecan had a reduced occurrence of severe neutropenia compared to placebo, at 40.6% and 75.6% respectively. Trilaciclib also reduced the duraction of severe neutropenia at 2 days compared with 8 days with placebo.

References

1. G1 Therapeutics’ Cosela (trilaciclib) included in two updated National Comprehensive Cancer Network® (NCCN) clinical practice guidelines in oncology. News release. G1 Therapeutics, Inc. March 25, 2021. Accessed April 16, 2021. https://bit.ly/3nrtZ4i
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