Trilaciclib Demonstrates Benefit Across Most Hematologic End Points for ES-SCLC Therapy

Administering trilaciclib (Cosela) prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC) led to a reduction in multilineage chemotherapy-induced myelosuppression and a lower incidence of chemotherapy-related hematologic adverse effects (AEs) versus placebo, according to pooled efficacy results from 3 randomized clinical trials published in Clinical Lung Cancer.¹

Impacts of these effects led to improved health-related quality of life (HRQOL) without impacting antitumor efficacy of 3 different chemotherapy regimens as frontline therapy or in relapsed-refractory disease.

“[P]atients have 2 major sources of physical suffering—the cancer itself and the side effects of chemotherapy,” Jared Weiss, MD, associate professor of medicine in the Division of Oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina Chapel Hill, said in a press release.² “Small cell [lung cancer] tends to present with bulky and rapidly growing central chest disease, which can compress airways and major vessels leading to shortness of breath, cough, and pain. While chemotherapy is great at shrinking the cancer and relieving these symptoms, it comes at the cost of side effects. Trilaciclib helps decrease these side effects which can help optimize quality of life.

One of the most common AEs associated with regimens for ES-SCLC—including first-line etoposide plus carboplatin [E/P], first-line E/P plus atezolizumab (Tecentriq), and topotecan (Hycamtin) for the second line and beyond—is myelosuppression, which downstream leads to neutropenia, anemia, and fatigue. The retrospective analysis of data from the double-blind, placebo-controlled, phase 2 portions of the multi-center G1T28-05 (NCT03041311), G1T28-02 (NCT02499770), and G1T28-03 (NCT02514447) studies examined how patients treated with these regimens were impacted by the addition of trilaciclib therapy. In all 3 trials, the CDK 4/6 inhibitor was administered intravenously at 240 mg/m2 prior to chemotherapy administration.

The primary end points related to myelosuppression were duration of severe neutropenia (DSN) in cycle 1 and the proportion of patients with SN occurrence during treatment. SN was defined as by absolute neutrophil count (ANC) lower than 0.5 × 109 cells/L. Secondary end points included trilaciclib’s effects on other neutrophil measures, RBC, and platelet lineages.

Improvements in DSN in cycle 1 were statistically significant with trilaciclib versus placebo, with means of (standard deviation) 0 days (1.8) and 4 days (5.1), respectively (P <.0001). Overall, 14 patients (11.4%) on trilaciclib experienced SN versus 63 patients (52.9%) in the placebo group (P <.0001).

Statistically significant improvements in the occurrence of granulocyte colony-stimulating factor (28.5% vs 56.3%; P <.0001), grade 3/4 anemia (20.3% vs 31.9%; P = .028), red blood cell transfusion on or after week 5 (14.5% vs 26.1%; P = .025), erythropoiesis-stimulating agents (3.3% vs 11.8%; P = .025), and grade 3/4 thrombocytopenia (19.5% vs 36.1%; P = .0067) were also observed with trilaciclib. Numerical improvements in febrile neutropenia with the agent were noted (3.3% vs 9.2%), but this was not found to be statistically significant (P = .089).

Benefits to therapy were made evident by a reduced necessity for supportive care interventions and hospitalizations due to chemotherapy-induced myelosuppression or sepsis and improvements in HRQOL, including physical functional wellbeing.

The only trilaciclib-related AEs occurring in at least 10% of patients were fatigue (11.5%) and nausea (10.7%), which were all low-grade except for 2 events of grade 3 fatigue.

“With trilaciclib added to standard therapy, my patients experience less hematologic toxicity, a reduced need for supportive care interventions and hospitalizations due to [chemotherapy-induced myelosuppression] or sepsis, and ultimately improvements in health-related quality of life domains, including fatigue, and physical and functional well-being,” Weiss said.

References

1. Weiss J, Goldschmidt J, Andric Z, et al. effects of trilaciclib on chemotherapy-induced myelosuppression and patient-reported outcomes in patients with extensive-stage small cell lung cancer: pooled results from three phase II randomized, double-blind, placebo-controlled studies. Clin Lung Cancer. March 25, 2021. doi: 10.1016/j.cllc.2021.03.010

2. G1 Therapeutics announces publication of pooled results from pivotal clinical program of Cosela (trilaciclib) in clinical lung cancer. News release. G1 Therapeutics, Inc. April 26, 2021. Accessed April 27, 2021. https://bit.ly/3eEaC43