Despite the many advances in cancer care, some adverse events (AEs) remain stubbornly common. Among the most frequent are myelosuppressive events, which occur when chemotherapy damages bone marrow cells that are the common source of red and white blood cells, as well as platelets. Findings from a 2016 study of AEs in patients who received chemotherapy for metastatic breast cancer showed that 33% had a hematological event, such as anemia or neutropenia, and these events were more costly than other types of AEs.1
Since the 1990s, clinicians have used granulocyte colony stimulating factor (G-CSF) to treat chemotherapy-induced neutropenia (CIN) by boosting white cells after chemotherapy. But G-CSF treatments can bring their own adverse effects, from bone pain, rashes, and headaches to more serious risks, including allergic reactions.2 What’s more, this reactive approach requires a different treatment for each type of hematological event—known as single-lineage interventions. What if a single treatment could head off all events, from anemia to CIN to thrombocytopenia?
The FDA opened the door to this approach in February 2021, when it approved trilaciclib (Cosela), a first-in-class therapy by G1 Therapeutics that works to prevent myelosuppression by arresting those bone marrow cells—called hematopoietic stem and progenitor cells—when they are at a key point before DNA replication.3 This use of “transient” CDK4/6 inhibition allows the cell to return to its role in white and red cell production after chemotherapy is administered, allowing the patient to receive treatment with reduced risk of hematological events.
AEs reported from trilaciclib use include fatigue; low levels of calcium, potassium, and phosphate; increased levels of aspartate aminotransferase; headache; and lung infections.3
Data from studies by leading oncologists, including those in top US community practices, suggest trilaciclib could be a game-changer in chemotherapy administration in extensive-stage small cell lung cancer (ES-SCLC), the indication for which it was approved.3 Already, company officials report, real-world data are showing dramatic drops in all-cause hospitalization. And some findings suggest that trilaciclib may enhance responses to immunotherapy in certain patients.
The therapy takes 30 minutes to administer via infusion before chemotherapy, and data show that consequently, patients not only have fewer serious AEs, they also report better health-related quality of life than those treated with placebo.4,5 Benefits appear especially pronounced for older patients, who may have more challenges with the effects of chemotherapy. European investigators analyzing results from several phase 2 studies found that the use of trilaciclib led to fewer dose reductions and longer periods without major hematological AEs.6
New Data From ASCO
In June, a post hoc analysis of data from phase 2 studies was presented during the 2022 Annual Meeting of the American Society of Clinical Oncology (ASCO). Investigators led by Jerome Goldschmidt, MD, a medical oncologist with Blue Ridge Cancer Care in Blacksburg, Virginia, found that patients with ES-SCLC treated with trilaciclib prior to chemotherapy had a lower incidence of myelosuppressive AEs, meaning fewer severe cases of anemia, neutropenia, and thrombocytopenia, than those taking placebo. The share of patients who had any event was lower among those treated with trilaciclib.7,8
Investigators calculated the number of patients who had a myelosuppressive event and the total number of events each experienced in both first-line and second- or third-line chemotherapy. Most patients (75%) were in the first-line setting. Only severe events (at least grade 3) were included in this analysis. Data for patients taking trilaciclib showed:
“Both the patients and the health care system at large bear the complications of myelosuppressive events such as neutropenia, anemia, and thrombocytopenia, so it is imperative that we achieve clinically meaningful reductions in myelosuppression in multiple cell lineages and its consequences utilizing novel therapies such as trilaciclib,” Goldschmidt said in a statement.7
Use in Other Cancers
The question now is whether trilaciclib can produce the same benefits in other cancers. Studies are underway that could expand its use to first-line treatment of colorectal cancer, bladder cancer, and triple-negative breast cancer (TNBC).9 Officials from G1 Therapeutics announced June 13 that the last of 326 patients had been randomly assigned in PRESERVE1 (NCT04607668), a phase 3 study of patients with metastatic colorectal cancer who received treatment with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, irinotecan)/bevacizumab.10 The study is scheduled to end in November.
In their review of therapies aimed at reducing CIN, Douglas W. Blayney, MD, and Lee Schwartzberg, MD, wrote that a key question about trilaciclib is whether the myeloprevention benefits “are tumor or chemotherapy type–dependent.” They note that data from a 2019 phase 2 study showed no benefit from trilaciclib in preventing gemcitabine/carboplatin-induced myelosuppression among patients with TNBC, “though benefits in progression-free survival and overall survival did occur in the trilaciclib cohort.”11,12
PRESERVE 2 (NCT04799249), a phase 3 study, will examine the use of trilaciclib with this chemotherapy combination in patients with metastatic TNBC. The study has 2 cohorts, based on phase 2 results that showed different findings based on PD-L1 status. Findings will be reported in 2024:13
Cohort 1 will study patients receiving first-line therapy, “regardless of PD-L1 status, who are PD-1/PD-L1 inhibitor therapy naïve.”
Cohort 2 will examine patients who are PD-L1 positive and who are receiving second-line therapy “following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting.”
In addition, trilaciclib is being studied in 45 patients with TNBC receiving treatment with sacituzumab govitecan, an antibody-drug conjugate.6 A separate study, PRESERVE 3 (NCT04887831), will examine trilaciclib in patients with metastatic bladder cancer who receive chemotherapy followed by avelumab. It is scheduled for completion in March 2023.14
Potential for Cost Savings
Can use of trilaciclib to prevent myelosuppressive AEs translate into cost savings for payers? Findings from a study first presented at the Academy of Managed Care Pharmacy 2021 meeting, which was funded by G1 Therapeutics, suggest the answer is yes. For this study, a budget impact model calculated the added costs or savings incorporating trilaciclib’s use across a 1-million-member health plan, compared with current costs without the drug.15
Based on finding that 301 patients would be eligible for treatment over a 5-year period, the investigators calculated that adopting trilaciclib would save the plan $801,254 over 5 years. The acquisition cost for the drug ($3,704,199) was offset by the reduction of AE management costs ($4,282,748).
G1 Therapeutics reported in its May earnings call that response to trilaciclib is very strong.16 “We continue to be encouraged by market reception for Cosela across payers, providers, and health care organizations,” said Andrew Perry, the company’s chief commercial officer. “Payer coverage, brand awareness, and intention to prescribe all remain strong, and we’re seeing that translate into physician endorsement.”
Real-world data. On the same call, Raj Malik, MD, chief medical officer, reviewed a real-world analysis using data from Integra Connect, which was presented during the National Comprehensive Cancer Network 2022 conference. The findings showed that use of trilaciclib prior to chemotherapy was associated with a 50% reduction in patients with grade 3 or higher hematological AEs (HAEs), and a 74% reduction in all-cause hospitalizations in the 21 days following treatment.17
“Among patients with a grade 3 or greater HAE in 1 blood cell lineage, the use of trilaciclib prior to chemotherapy was associated with an 86% reduction in thrombocytopenia, a 58% reduction in anemia, and a 57% reduction in neutropenia,” compared with patients who did not receive the infusion, Malik said.
The Integra data show a “remarkable impact” on all-cause hospitalization, he continued. “No patient receiving trilaciclib prior to chemo[therapy] was hospitalized between days 8 and 16 after initiation of chemotherapy, compared with just over 7% of patients receiving chemo[therapy] alone. And only 1 patient, or 4.8% who received trilaciclib, was hospitalized between days 1 and 21, compared with 19% of patients who received chemo[therapy] only.
“These data are very compelling,” Malik said. “We look forward to presenting more real-world data as they become available.”
1. Rashid N, Koh HA, Baca HC, Lin KJ, Malecha SE, Masaquel A. Economic burden related to chemotherapy-related adverse events in patients with metastatic breast cancer in an integrated health care system. Breast Cancer (Dove Med Press). 2016;8:173-181. doi:10.2147/BCTT.S105618
2. Filgrastim, G-CSF injection. Cleveland Clinic. Accessed July 25, 2022. https://my.clevelandclinic.org/health/drugs/19431-filgrastim-g-csf-injection.
3. FDA approves drug to reduce bone marrow suppression caused by chemotherapy. News release. FDA. February 12, 2021. Accessed July 25, 2022. https://bit.ly/3OwLNqr
4. Daniel D, Kuchava V, Bondarenko I, et al. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: a multicentre, randomised, double-blind, placebo-controlled phase II trial. Int J Cancer. 2020;148(10):2557-2570. doi:10.1002/ijc.33453
5. Hussein M, Maglakelidze M, Richards DA, et al. Myeloprotective effects of trilaciclib among patients with small cell lung cancer at increased risk of chemotherapy-induced myelosuppression: pooled results from three phase 2, randomized, double-blind, placebo-controlled studies. Cancer Manag Res. 2021;13:6207-6218. doi:10.2147/CMAR.S313045
6. Gómez MD, Csöszi T, Jaal J, et al. Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer. Int J Cancer. 2021;149(7):1463-1472. doi:10.1002/ijc.33705
7. Data presented at ASCO demonstrate trilaciclib helps protect against severe neutropenia, severe anemia, and severe thrombocytopenia when given to extensive-stage small cell lung cancer (ES-SCLC) patients prior to chemotherapy. News release. G1 Therapeutics, Inc. June 2, 2022. Accessed July 24, 2022. https://bit.ly/3S2DPIQ
8. Goldschmidt JH, Weiss J, Zhou J, et al. Impact of trilaciclib on multilineage chemotherapy-induced myelosuppression events in patients with extensive-stage small cell lung cancer: post-hoc analyses of data from randomized clinical trials. J Clin Oncol. 2022;40(suppl 16):8568. doi:10.1200/JCO.2022.40.16_suppl.8568
9. Pipeline overview. G1 Therapeutics. Accessed July 25, 2022. https://www.g1therapeutics.com/science/pipeline/
10. G1 Therapeutics announces completion of enrollment in global multicenter phase 3 clinical trial of trilaciclib in patients with metastatic colorectal cancer. News release. G1 Therapeutics. June 13, 2022. Accessed July 25, 2022. https://bit.ly/3PYocAl
11. Blayney DW, Schwartzberg L. Chemotherapy-induced neutropenia and emerging agents for prevention and treatment: a review. Cancer Treat Rev. 2022;109:102427. doi:10.1016/j.ctrv.2022.102427
12. Tan AR, Wright GS, Thummala AR, et al. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019;20(11):1587-1601. doi:10.1016/S1470-2045(19)30616-3
13. Trilaciclib, a CDK 4/6 inhibitor, in patients receiving gemcitabine and carboplatin for metastatic triple-negative breast cancer (TNBC) (PRESERVE 2). ClinicalTrials.gov. Updated May 12, 2022. Accessed July 25, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04799249
14. Trilaciclib, a CDK 4/6 inhibitor, in patients with advanced/metastatic bladder cancer receiving chemotherapy then avelumab (PRESERVE3). ClinicalTrials.gov. Updated June 9, 2022. Accessed July 25, 2022. https://clinicaltrials.gov/ct2/show/NCT04887831
15. Abraham I, Goyal A, Deniz B, et al. Budget impact analysis of trilaciclib for decreasing the incidence of chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer in the United States. J Manag Care Spec Pharm. 2022;28(4):435-448. doi:10.18553/jmcp.2022.21379
16. G1 Therapeutics, Inc. (GTHX) CEO Jack Bailey on Q1 2022 results – earnings call transcript. Seeking Alpha. May 4, 2022. Accessed July 25, 2022. https://bit.ly/3ONvCpb
17. Scott J, Slack D, Gingras L, Chioda M, Huang H. Burden of myelosuppression among patients with extensive-stage small cell lung cancer treated with chemotherapy in a community oncology setting. J Natl Comp Cancer Netw. 2022;20(3.5). doi:10.6004.jnccn.2021.7181