Trilaciclib Before Chemo Results in Real-World Reduction of Myelosuppressive Hematologic AEs in ES-SCLC

The use of trilaciclib (Cosela) prior to chemotherapy resulted in a 50% reduction in the percent of patients with extensive-stage small cell lung cancer (SCLC) who had grade 3 or higher myelosuppressive hematologic adverse effects (HAEs) in at least 1 blood cell lineage, according to real-world data from a retrospective study presented during the 2022 National Comprehensive Cancer Network (NCCN) Annual Conference.¹

Of the 3277 patients who received chemotherapy, 57.4% experienced at least 1 grade 3 or higher myelosuppressive HAE; this included 34.0% with grade 3 or higher anemia, 44.6% with grade 3 or higher neutropenia, and 33.3% with grade 3 or higher thrombocytopenia. Moreover, 23.0% of patients experienced grade 3 or higher neutropenia and thrombocytopenia, 20.3% had grade 3 or higher anemia and neutropenia, and 19.6% had grade 3 or higher anemia and thrombocytopenia. Notably, 14.5% of these patients experienced all 3 myelosuppressive HAEs at grade 3 or higher.

Among the 21 patients who received trilaciclib in addition to chemotherapy, 28.6% of patients experienced at least 1 grade 3 or higher myelosuppressive HAE; 14.3% of patients had grade 3 or higher anemia, 19.0% had grade 3 or higher neutropenia, and 4.8% had grade 3 or higher thrombocytopenia. Notably, less than 5% of these patients experienced myelosuppressive HAEs in 2 or more lineages, and no patients experienced HAEs in all 3 lineages.

“The real-world burden of myelosuppressive HAEs among patients receiving chemotherapy, and the resulting hospitalizations, are routinely underestimated in the community oncology setting,” lead study author Jeffrey Scott, MD, chief medical officer of Integra Connect, stated in a press release.² “Importantly, these data also capture the first real-world experience of using trilaciclib prior to chemotherapy. Among those patients, the use of trilaciclib nearly eliminated not only grade 3 or higher HAEs associated with multilineage myelosuppression but also all-cause hospitalizations.”

Cytotoxic chemotherapy continues to serve as a standard treatment for patients with ES-SCLC, but myelosuppressive HAEs have been commonly associated with this approach.^3,4 HAEs have typically been managed with dose delays or reductions and/or supportive care interventions like granulocyte colony–stimulating factor (G-CSF), erythropoiesis-stimulating agents (ESAs), and red blood cell (RBC) transfusions.

In February 2021, trilaciclib was approved by the FDA to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving certain types of chemotherapy for ES-SCLC. Subsequently, in March 2021, the agent was added to the NCCN guidelines as a prophylactic option to manage chemotherapy-induced myelosuppression in those with ES-SCLC.⁵

In the observational study, investigators sought to assess the prevalence of grade 3 or higher myelosuppressive HAEs and associated health care resource utilization in the community oncology setting in patients with ES-SCLC who just received chemotherapy, and in those with ES-SCLC who received chemotherapy and trilaciclib.

For the primary analysis, investigators identified patients whowere treated with chemotherapy between January 1, 2015, and March 31, 2021. Patients with ES-SCLC who were administered trilaciclib as part of their index chemotherapy regimen between January 1, 2017, and December 2, 2021, were included in the secondary analysis.

For both analyses, a data-driven algorithm was leveraged to identify patients with ES-SCLC based on chemotherapy treatment and rule out those who received treatment or tested positive for non–small cell lung cancer. Specifically, those who received afatinib (Gilotrif), bevacizumab (Avastin), cetuximab (Erbitux), erlotinib (Tarceva), fluorouracil, nab-paclitaxel (Abraxane), nivolumab (Opdivo), osimertinib (Tagrisso), paclitaxel, pemetrexed, or vinorelbine, or who had tested positive for KRAS, EGFR, HER2, BRAF, ALK, MET, ROS-1, RET, or NTRK1/2/3 mutations were ineligible.

Patients were followed from the start of treatment with chemotherapy through death, loss to follow-up, or study completion. Myelosuppressive HAEs were detected using laboratory values based on Common Terminology Criteria for Adverse Events v5.0 definitions, and the analyses examined the prevalence and frequency of grade 3 or higher HAEs, treatment patterns, supportive care use, and all-cause hospitalizations.

The median age was 68 years among the patients treated with only chemotherapy vs 70 years in those who also received trilaciclib. In the chemotherapy-alone group, 50.4% of patients were male vs 47.6% in the chemotherapy/trilaciclib group. In the chemotherapy-alone and trilaciclib groups, most patients were White, at 60.1% and 76.2%, respectively. In the chemotherapy-alone arm, 23.9% of patients had an ECOG performance status of 0, 40.9% had a status of 1, 15.7% had a status of 2, and 4.2% had a status of 3 or higher; these rates were 38.1%, 47.5%, 14.3%, and 0%, respectively, in the trilaciclib group.

In the chemotherapy arm, 65.7% of patients received chemotherapy alone, and 70.3% of those patients specifically received etoposide plus carboplatin as the index regimen. Additionally, 34.3% of patients received chemotherapy plus immunotherapy; 89.3% of these patients received etoposide plus carboplatin and atezolizumab (Tecentriq).

Furthermore, 83.9% of patients in the chemotherapy arm were administered a long-acting G-CSF; 61.1% of these patients received this within 3 days of treatment initiation. Among these 2751 patients, 30.3% experienced grade 3 or higher anemia and 29.4% had grade 3 or higher thrombocytopenia. ESAs were given to 14.5% of patients in the chemotherapy arm (n = 476); 37.0% of these patients had grade 3 or higher neutropenia and 51.9% of patients had grade 3 or higher thrombocytopenia. RBC transfusions were received by 10.7% of patients in the chemotherapy arm. Moreover, 7.4% of patients were hospitalized between days 8 and 16 post index, and 18.8% were hospitalized between days 1 and 21 post index.

In the 21 patients who received chemotherapy and trilaciclib, 71.4% received long-acting G-CSF; 47.6% of these patients received it within 3 days of the index date. Additionally, 1 patient received an RBC transfusion, and no patients received platelet transfusions at any time following the index date. Notably, none of these patients were hospitalized between days 8 and 16 post index, and only 1 patient was hospitalized between days 1 and 21 post index.

The study authors noted hospitalizations may be under captured due to data limitation, and the results may not be generalizable beyond the community oncology setting. Due to the small sample size of patients who received trilaciclib, further studies with larger populations are recommended to enable the comparison between the 2 treatment options.

“The myelotoxic impacts of chemotherapy in patients with ES-SCLC—including grade 3 or higher neutropenia, anemia, and thrombocytopenia—pose a considerable burden to both patients and to the health care system at large in terms of associated health care resources required to treat them,” Huan Huang, co-study author and director of Health Economics and Outcomes Research at G1 Therapeutics, added in the press release. “While the numbers in the trilaciclib dataset are small, these new data add to a growing body of real-world data cataloguing the extent of this burden in patients with ES-SCLC and the need for innovative therapies, such as trilaciclib, to reduce them.”

References

1. 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. Presented at: 2022 NCCN Annual Meeting; March 31-April 2, 2022; Virtual. Accessed April 5, 2022.
2. New real-world data show potential of trilaciclib to reduce the substantial burden of myelosuppression in patients with extensive-stage small-cell lung cancer treated with chemotherapy. News release. G1 Therapeutics; March 31, 2022. Accessed April 5, 2022. https://bit.ly/3xapBxo
3. Kurtin S. Myeloid toxicity of cancer treatment. J Adv Pract Oncol. 2012;3(4):209-24.
4. Aapro M, Beguin Y, Bokemeyer C, et al. Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(suppl 4):iv96-iv110. doi:10.1093/annonc/mdx758
5. Hematopoietic growth factors V1.2022. National Comprehensive Cancer Network. Accessed April 5, 2022. https://bit.ly/3JaNurc