Trilaciclib Prior to Chemotherapy Reduces Need for Supportive Care for Chemo-Induced Myelosuppression in ES-SCLC

On or after week 5 of treatment with chemotherapy, trilaciclib reduced the need for supportive care therapies in patients with extensive-stage small-cell lung cancer.

Trilaciclib (Cosela) prior to chemotherapy was shown to significantly reduce the use of supportive care therapies for chemotherapy-induced myelosuppression on or after week 5 of chemotherapy for patients with extensive stage small cell lung cancer (ES-SCLC), according to a press release from G1 Therapeutics.1

The findings came from a retrospective analysis that analyzed 3 different phase 2 randomized trials.2 The first study examined trilaciclib in combination with etoposide and carboplatin in ES-SCLC (NCT02499770); the second assessed carboplatin, etoposide, and atezolizumab with or without trilaciclib in ES-SCLC NCT03041311), and the last evaluated trilaciclib in patients with ES-SCLC who were receiving treatment with topotecan chemotherapy (NCT02514447). Patients who were treated with trilaciclib compared with placebo on or after week 5 had a significantly lower use of granulocyte colony-stimulating factors (G-CSFs; 28.5% vs 56.3%; P <.0001), erythropoiesis-stimulating agents (ESAs; 3.3% vs 11.8%; P = .0254), and red blood cell (RBC) transfusions (14.6 vs 26.1; P = .252).

“The results from our analysis show clear myeloprotection benefits associated with the administration of trilaciclib prior to chemotherapy in patients with ES-SCLC,” lead author Renata Ferrarotto, MD, an associate professor of the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center, said in a press release. “By reducing the need for associated supportive care, trilaciclib has the potential to reduce both the societal and economic burden of chemotherapy-induced myelosuppression.”

Between the 3 trials, 242 patients were randomized to receive either trilaciclib (n = 123) or placebo (n = 119). Eligible patients were required to be at least 18 years of age with measurable disease by response evaluation criteria in solid tumors. Additionally, as ECOG performance status or 0 to 2 and adequate organ function were required.

Across all trials, the use of ESAs and primary prophylaxis with G-CSFs were not allowed during cycle 1. However, the therapeutic use of G-CSF was acceptable. Supportive care measures were allowed during cycle 2 or higher.

Other findings from the pooled analysis indicated that during cycle 1, the duration of severe neutropenia was shorter in the trilaciclib group than the placebo group with a mean of 0 days compared with 4 days. During treatment, 11.4% (n = 14) of patients in the trilaciclib group and 52.9% (n = 63) in the placebo group had severe neutropenia (adjusted relative risk [aRR], 0.509; 95% CI, 0.120-0.351; P <.0001).

During cycle 1, the duration and occurrence of severe neutropenia and from the use of trilaciclib remained statistically significant (P <.0001). Throughout cycles 1 to 4, trilaciclib reduced the mean duration of severe neutropenia and occurrence of severe neutropenia irrespective of G-CSF.

A total of 20.3% of patients in the trilaciclib group had grade 3 or 4 anemia vs 31.9% in the placebo group (aRR, 95% CI, 0.620; 95% CI, 0.405-0.949; P = .0279). On or after week 5, 3.3% of patients in the trilaciclib group used ESAs compared with 11.8% in the placebo group (P = .0254), and 14.6% of those in the trilaciclib group vs 26.1% of those in the placebo group were given RBC infusions (P = .0252).

Notably, RBC transfusions in the placebo group almost doubled over time from 8.4% during cycle 1 to 14.3% during cycle 4, and those in the trilaciclib group remained somewhat stable from 5.8% to 8.3%.

Investigators noted a high concordance between RBC transfusions on or after week 5 and grade 3/4 anemia regardless of treatment group. Concordance between treatment with ESA and grade 3/4 anemia was lower, but significant with both the trilaciclib group (P = .0057) and the placebo group (P <.0001). Additionally, among those who experienced grade 3/4 anemia, concordance between the administration of ESA and RBC transfusions on or after week 5 was low in both the trilaciclib group (P = .1661) and the placebo group (P = .8969).

On or after week 5, 20.2% (n = 49) of patients had 87 RBC transfusions. Additionally, 87.8% (n = 43) of patients had at least 1 RBC transfusion that was considered to be clinically appropriate, and 22.4% (n = 11) that was thought to be clinically inappropriate.

References

1. Retrospective analysis of pooled results from three studies shows Cosela (Trilaciclib) reduced use of supportive care interventions in extensive stage small cell lung cancer patients who receive the drug prior to chemotherapy. News Release. G1 Therapeutics. October 7, 2021. Accessed October 14, 2021. https://yhoo.it/3p2r9W5 

2. Ferrarotto R, Anderson I, Medgyasszay B, et al. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: pooled analysis of three randomized phase 2 trials. Cancer Med. 2021;10(17):5748-5756. doi:10.1002/cam4.4089