Trilaciclib Enhances Survival in ES-SCLC, According to Real-World Data

Holographic concept of lung cancer display, lung disease: © catalin - stock.adobe.com

Trilaciclib (Cosela) administered prior to platinum-based chemotherapy shows lower rates of hospitalization and cytopenia events in patients with extensive-stage small cell lung cancer (ES-SCLC), and may improve survival, according to real-world data presented at the 2023 American Society of Clinical Oncology (ASCO) Quality Care Symposium.¹

Trilaciclib is a transient CDK4/6 inhibitor that is given to patients via intravenous infusion prior to treatment with chemotherapy.² The novel therapeutic approach temporarily blocks progression through the cell cycle to protect the bone marrow from damage caused by cytotoxic therapy, and aims to better long-term immune surveillance. The agent is currently undergoing evaluation in multiple tumor types.

Four poster presentations from the meeting looked at real-world analyses of trilaciclib given to patients with ES-SCLC before treatment with chemotherapy and showed there to be a consistent impact of chemotherapy-induced myelosuppressive events, including severe neutropenia, thrombocytopenia, and anemia, on those treated with platinum-based chemotherapy, as well as the resulting impact on healthcare resource utilization (HRU).¹

“The burden of chemotherapy-induced myelosuppression not only puts patients at risk for serious adverse events but can also stress the healthcare system,” said Raj Malik, MD, chief medical officer at G1 Therapeutics, in a press release.1 “Findings from these real-world analyses demonstrate the need to protect patients from the harmful side effects of chemotherapy so that they can continue their treatment. Trilaciclib offers the potential to transform the treatment experience, and these new data underscore the results we’ve seen across multiple analyses showing the positive impact of proactive treatment with trilaciclib.”

In the first observational study presented at the ASCO Quality Care Symposium, cytopenia-related outcomes and HRU were compared in a real-world setting between patients with ES-SCLC who received trilaciclib before chemotherapy vs patients who did not.

Between January 2020 and April 2023, structured electronic medical records from EMOL Health’s database were examined and descriptive analyses were performed for patient baseline characteristics and outcomes between the 2 matched cohorts.

Findings revealed that among the 77 patients given trilaciclib prior to chemotherapy in cycles 1-4, rates of grade ≥3 myelosuppressive hematologic adverse events (HAEs) and cytopenia-related HRU were lower than the 77 patients in the matched comparison cohort who were not treated with trilaciclib. Grade ≥3 HAEs in ≥1 lineage were observed in 11.2% of trilaciclib-treated patients vs 30.7% of patients in the comparison cohort, grade ≥3 HAEs in ≥2 lineages were seen in 1.2%vs 13.5%, and grade ≥3 HAEs in 3 lineages were seen in 0.4% vs 4.9%.

Among those given trilaciclib vs those not receiving trilaciclib, granulocyte colony-stimulating factor (G-CSF) administered any time during the cycle was reduced by 60.7% (25.6% v 65.2%). Red blood cell (RBC) transfusions and erythropoiesis-stimulating agent use were also reduced by 84.4% (1.7% v 10.9%) and 42.2% (3.7% vs. 6.4%), respectively. Once investigators adjusted for age, sex, index line of therapy, and number of chemotherapy cycles receiving trilaciclib, chances of developing an event of grade ≥3 myelosuppression in ≥1, ≥2, and 3 lineages were reduced by 70%, 90%, and 96%, respectively, among patients given trilaciclib.

Though not statistically significant, the odds of all-cause hospitalization were reduced by 51% when patients were treated with trilaciclib. All other results were statistically significant.

In another study which assessed the real-world rates of hospitalizations and cytopenia events in patients with ES-SCLC treated with chemotherapy and trilaciclib vs patients who did not receive trilaciclib, data from the 100% Medicare Fee-for-Service and the Inovalon MORE2 closed claims databases between February 2020 and September 2023 were used. A total of 132 patients were included in the study and given trilaciclib prior to chemotherapy, and 11,940 patients did not receive trilaciclib.

Looking at the hospitalization outcomes, trilaciclib use led to a lower rate of all-cause per patient per month hospitalizations during follow-up (0.14±0.25 v 0.19±0.27; P <.01). Patients given trilaciclib were also less likely to be hospitalized within 90 days after the start of chemotherapy (21.2% v 32.1%; P <.01), vs patients who did not receive trilaciclib.

Patients given trilaciclib prior to their chemotherapy had a statistically significantly lower risk of febrile neutropenia (relative risk, 15.5%; P =.03) and numerically lower risk of anemia, neutropenia and thrombocytopenia in the 90-day post-index period compared with those who did not receive trilaciclib.

Additionally, trilaciclib use was associated with a numerically higher rate of survival at 6 months (84.1%) vs patients not treated with trilaciclib (72.3%). The survival hazard ratio was 0.63 (95% CI, 0.35-1.14; P =.13) vs patients who were not treated with trilaciclib.

Another study utilized data from Tennessee Oncology to evaluate the burden of myelosuppression among patients with ES-SCLC. This was assessed by HAEs, including anemia, neutropenia, and thrombocytopenia. Investigators also looked at cytopenia-related and all-cause HRU among the same population.

A total of 152 patients with ES-SCLC were included and treated with chemotherapy with or without immunotherapy. Trilaciclib was not administered to these patients at any point in their therapy.

Of those enrolled, the prevalence of single- and multi-lineage myelosuppression during the 10 month average follow-up period after initiation of chemotherapy showed that 63.8% of patients had grade ≥ 3 myelosuppressive HAE in ≥ 1 lineage.Grade ≥ 3 neutropenia was observed in 49.3% of patients, grade 3 anemia was seen in 29.0%, and grade ≥ 3 thrombocytopenia was observed in 28.3% of patients. Additionally, 32.2% had grade ≥3 HAEs in ≥2 lineages, and 10.5% had grade ≥3 HAEs in 3 lineages.

During the follow-up period, cytopenia-related and all-cause HRU showed that 76.3% of patients received G-CSF administration at any time during follow-up, 30.3% had a RBC transfusion, 57.9% had at least 1 inpatient admission, 67.8% had at least 1 visit to the emergency room, and all patients had at least 1 outpatient visit.

Consistent with other studies, these results show that there is high patient burden that correlates with traditional management of myelosuppression in patients with ES-SCLC. Treatments that can protect bone marrow from myelosuppression have potential to reduce such burden, but more research is warranted.

Lastly, a retrospective observational study looked at patients with ES-SCLC and sought to examine the link between patient attributes and the risk of chemotherapy-induced myelosuppression. The study used real-world data from the U.S. Oncology Network’s iKnowMed electronic health record system.

According to findings from the study, all patients with ES-SCLC are at a similar risk of myelosuppressive events. This was irrespective of patient characteristics, including age, sex, race, ECOG performance status, and baseline lab values. None of these characteristics were found to be risk factors for myelosuppressive events for patients with ES-SCLC being treated with chemotherapy.

Further, investigators noted that delays and holds with treatment were associated with a higher risk of myelosuppressive events among patients, suggesting that the ways in which patients present during their initial visits are not always predictive of myelosuppressive events.

REFERENCES:

1. Real world data indicate that trilaciclib reduces hospitalizations and myelosuppressive events and may improve survival in patients with extensive-stage small cell lung cancer (ES-SCLC). News Release. G1 Therapeutics, Inc. October 27, 2023. Accessed October 30, 2023. https://tinyurl.com/y3pht6bs

2. Trilaciclib. G1 Therapeutics, Inc. Accessed October 30, 2023. https://tinyurl.com/2p9amjy6