Efficacy and Safety of Trilaciclib for the Prevention of Chemotherapy‐Induced Myelosuppression in Patients With Solid Tumors: A Systematic Review and Meta‐Analysis

ABSTRACT

Trilaciclib, a cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor administered before chemotherapy, reduces chemotherapy‐induced myelosuppression (CIM) in extensive‐stage small cell lung cancer (ES‐SCLC), but its efficacy across solid tumors remains unclear. This meta‐analysis evaluated the efficacy and safety of trilaciclib in solid tumor patients receiving chemotherapy. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception to January 21, 2026. Randomized controlled trials (RCTs) and cohort studies comparing chemotherapy with or without trilaciclib were included. Primary outcomes were severe neutropenia (SN), febrile neutropenia (FN), duration of severe neutropenia (DSN), Grade 3/4 leukopenia, and granulocyte colony‐stimulating factor (G‐CSF) use. Secondary outcomes included other hematologic toxicities, supportive care interventions, and efficacy outcomes. Ten studies involving 1172 patients (six RCTs and four cohort studies) were identified. Trilaciclib significantly reduced SN (OR, 0.14; 95% CI, 0.06–0.31; p < 0.001), FN (OR, 0.19; 95% CI, 0.11–0.36; p < 0.001), Grade 3/4 leukopenia (OR, 0.25; 95% CI, 0.13–0.46; p < 0.001), and G‐CSF use (OR, 0.36; 95% CI, 0.18–0.71; p = 0.0087), and shortened DSN (MD, −2.30 days; 95% CI, −4.28 to −0.31; p = 0.0309). It also reduced Grade 3/4 anemia and thrombocytopenia and decreased use of erythropoiesis‐stimulating agents, red blood cell transfusions, and platelet transfusions. Overall survival showed a borderline improvement (HR, 0.84; 95% CI, 0.71–0.99; p = 0.0373), while no significant differences were observed in progression‐free survival, overall response rate, or non‐hematologic adverse events. Subgroup analyses suggested greater benefit in ES‐SCLC. Overall, trilaciclib before chemotherapy significantly reduced CIM and supportive care needs, with no apparent compromise in antitumor efficacy and more pronounced effects in ES‐SCLC.

This systematic review and meta‐analysis evaluated the efficacy and safety of trilaciclib for preventing chemotherapy‐induced myelosuppression in patients with solid tumors. Trilaciclib significantly reduced severe neutropenia, febrile neutropenia, and supportive care requirements with a possible overall survival benefit and no apparent compromise in progression‐free survival or overall response rate. Benefits were most consistent in extensive‐stage small cell lung cancer.

1. Introduction

Chemotherapy is widely used in the systemic treatment of many malignancies, including small cell lung cancer, triple‐negative breast cancer, and colorectal cancer [1, 2, 3]. However, patients receiving standard chemotherapy regimens often develop chemotherapy‐induced myelosuppression (CIM), a clinically significant toxicity that can compromise treatment delivery and efficacy.

CIM typically manifests as neutropenia, anemia, and thrombocytopenia, which not only increase the risks of infection and bleeding but also often necessitate dose reductions or treatment delays [4]. Such modifications may reduce chemotherapy dose intensity, potentially compromising survival outcomes and patients' quality of life [5]. Current management of CIM primarily relies on supportive interventions, such as granulocyte colony‐stimulating factors (G‐CSF), erythropoiesis‐stimulating agents (ESAs), and blood transfusions [6]. Although widely used, these approaches are lineage‐specific and are typically initiated after myelosuppression has already occurred, limiting their ability to provide comprehensive and proactive bone marrow protection.

Trilaciclib, a selective and reversible cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor, received FDA approval in 2021 as the first myeloprotective agent for patients with extensive‐stage small cell lung cancer (ES‐SCLC) treated with chemotherapy [7]. Given before chemotherapy, trilaciclib transiently arrests CDK4/6 dependent hematopoietic stem and progenitor cells (HSPCs) in G1 phase, thereby protecting them from chemotherapy‐induced cytotoxic damage [8]. This mechanism differentiates trilaciclib from conventional supportive care strategies and enables proactive protection against multilineage myelosuppression.

Clinical trials in ES‐SCLC have demonstrated that trilaciclib significantly reduces the incidence and duration of severe neutropenia (DSN) and other hematologic toxicities without compromising survival outcomes [9, 10, 11]. However, evidence across different malignancies remains inconsistent. While a Phase III trial in metastatic colorectal cancer (mCRC) reported reductions in severe neutropenia (SN) duration and other bone marrow toxicities [12], a study conducted in metastatic triple‐negative breast cancer (mTNBC) did not demonstrate significant improvements in myelosuppression‐related endpoints compared with chemotherapy alone [13]. These inconsistent results suggest that the effects of trilaciclib may vary across tumor types. In addition, previous meta‐analyses have primarily focused on randomized controlled trials (RCTs) and largely concentrated on small cell lung cancer, with limited inclusion of real‐world evidence from observational studies [14]. Collectively, these limitations highlight the need for a more comprehensive evaluation of trilaciclib across different malignancies and study designs.

In this study, we conducted a systematic review and meta‐analysis including both RCTs and observational cohort studies to evaluate the efficacy and safety of intravenous trilaciclib given prior to chemotherapy in adults with advanced or metastatic solid tumors, with a focus on its role in preventing CIM and its impact on treatment outcomes.

2. Methods

2.1. Study Design

This systematic review and meta‐analysis followed Cochrane Handbook recommendations [15] and was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines [16]. The review protocol was prospectively registered in PROSPERO on August 14, 2025 (CRD420251123592). The protocol prespecified the eligibility criteria, including adult patients with solid tumors receiving myelosuppressive chemotherapy, with trilaciclib compared with placebo or standard care. Both RCTs and observational studies were eligible. Prespecified outcomes included SN, febrile neutropenia (FN), DSN, G‐CSF/ESA administration, red blood cell (RBC)/platelet transfusion requirements, as well as survival outcomes and adverse events.

2.2. Literature Search Strategy

A systematic search was carried out across PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to January 21, 2026, using the terms “Trilaciclib,” “Cosela,” and “G1T28.”

2.3. Eligibility Criteria

Studies were eligible if they met the following criteria:

1. adult patients aged ≥ 18 years with malignant solid tumors;

2. receipt of chemotherapy as the primary intervention;

3. comparison of chemotherapy alone versus chemotherapy combined with trilaciclib;

4. reporting of efficacy outcomes related to CIM, including the incidence of neutropenia, anemia, or thrombocytopenia, as well as the use of supportive interventions and safety outcomes.

No restrictions were applied regarding tumor type, disease stage, or line of therapy. Both RCTs and observational studies were eligible for inclusion.

2.4. Study Selection and Data Extraction

Study selection was carried out independently by two investigators in accordance with predefined eligibility criteria. After an initial screening of titles and abstracts, full‐texts of potentially relevant studies were evaluated. Data were then independently extracted using a standardized Excel template, with any discrepancies resolved through discussion with a third investigator. Extracted information included study characteristics (title, authors, publication year, study design, and duration), participant characteristics (age, sample size, and population details), interventions and comparators, as well as clinical outcomes and adverse events.

2.5. Outcome Measurement

The primary outcomes were predefined as key measures of CIM, including the occurrence of SN, FN, DSN, Grade 3/4 leukopenia, and the use of G‐CSF.

The secondary outcomes evaluated broader safety and clinical efficacy. Safety assessments comprised other treatment‐related adverse events, such as anemia, thrombocytopenia, nausea, vomiting, diarrhea, and fatigue. Additionally, the use of other supportive care interventions, such as ESA and RBC or platelet transfusions, was recorded. To assess the overall treatment effect, clinical efficacy outcomes were analyzed, including overall survival (OS), progression‐free survival (PFS), and overall response rate (ORR).

2.6. Risk of Bias and Quality Assessment

The risk of bias of RCTs was assessed using the Risk of Bias 2 tool [17]. Five domains were evaluated, including the selection of the reported result, measurement of the outcome, missing outcome data, deviations from intended interventions, and randomization process. Each domain was assessed as having low risk, some concerns, or high risk of bias, and an overall risk of bias judgment was then derived.

The methodological quality of non‐randomized studies was evaluated using the Methodological Index for Non‐Randomized Studies (MINORS) tool [18]. For comparative studies, this instrument includes 12 items, each scored from 0 to 2, with a maximum total score of 24. Higher scores reflect better methodological quality.

All assessments were conducted independently by two reviewers, with any discrepancies resolved through discussion to reach consensus.

2.7. Data Analysis

All statistical analyses were performed using R (version 4.5.1) with the meta package (version 8.2.1). Effect estimates were pooled and presented as forest plots. For dichotomous outcomes, odds ratios (ORs) with 95% confidence intervals (CIs) were used, while continuous outcomes were summarized as mean differences (MDs) with 95% CIs. Time‐to‐event outcomes, including OS and PFS, were expressed as hazard ratios (HRs) with 95% CIs.

When multiple intervention arms shared a common control group, the intervention arms were combined into a single group to avoid double‐counting of participants. For dichotomous and continuous outcomes, the numbers of events and participants, and the means and standard deviations of the intervention arms, respectively, were combined using the standard method recommended by the Cochrane Handbook [15]. For time‐to‐event outcomes, a reported HR based on the combined intervention groups was used where available. When sample sizes differed across outcomes within a study, we used the sample size corresponding to the analysis population in which the outcome was originally analyzed (e.g., in Tan et al. 2019 [13], the control group included 34 patients in the intention‐to‐treat population and 30 patients in the safety population).

Statistical heterogeneity was evaluated using Cochran's Q test and the I² statistic, with I² > 50% indicating substantial heterogeneity. A common‐effect model was used for outcomes with I² ≤ 50%, whereas a random‐effects model was used for outcomes with I² > 50%. When common‐effect and random‐effects models produced different conclusions, the result from the model selected according to this prespecified heterogeneity‐based rule was used for primary interpretation. Sensitivity analysis was performed using a leave‐one‐out method. Additionally, subgroup analyses of primary outcomes were conducted according to tumor type and study design to explore potential sources of heterogeneity and assess the robustness of treatment effects. Statistical significance was defined as a two‐sided p value < 0.05.

3. Results

3.1. Study Selection and Baseline Characteristics

A total of 533 records were identified in the initial search across four databases. After removal of duplicates, 298 studies were retained for screening. Following title, abstract, and full‐text assessment, 10 studies (6 RCTs and 4 observational studies) were included in the meta‐analysis. The study selection process is presented in Figure 1.

FIGURE 1.

PRISMA 2020 flow diagram showing study selection process.

A total of 1172 patients were included, with 601 receiving trilaciclib plus chemotherapy and 571 receiving chemotherapy alone. The studies were conducted across multiple countries and enrolled patients with various solid tumors. Among the included studies, seven focused on ES‐SCLC, one on TNBC, one on mCRC, and one on esophageal squamous cell carcinoma (ESCC). Trilaciclib was administered at a standard dose of 240 mg/m² before the initiation of chemotherapy. Detailed study characteristics are presented in Table 1.

TABLE 1.

Baseline characteristics of the included studies.

Study, year	Study type and duration	Study population	Line of therapy	Group	Chemotherapy regimen	Patient number	Age (years)	Male (%)	Trilacicli.b. dose	Median follow‐up
Weiss, 2019 [9]	Phase II RCT (Jun 2015–Feb 2019)	≥ 18 years, histologically or cytologically confirmed ES‐SCLC	1 L	Control	E/C plus placebo	38	66 (39–86)	71.1	240 mg/m2 IV prior to chemotherapy	NR
				Experimental	E/C plus Trilaciclib	39	64 (49–82)	69.2
Tan, 2019 [13]	Phase II RCT (Feb 2017–May 2018)	≥ 18 years, with recurrent or metastatic triple‐negative breast cancer who had no more than two previous lines of chemotherapy	0–2 prior lines	Control	G/C plus placebo	34	55 (43–64)	0	240 mg/m2	8.4 months
				Experimental	G/C plus Trilaciclib (D1 + D8)	33	55 (47–66)	3		12.7 months
				Experimental	G/C plus Trilaciclib (D2 + D9)	35	58 (49–65)	0		12.9 months
Hart, 2020 [10]	Phase II RCT (Oct 2015—Oct 2021)	≥ 18 years, with confirmed diagnosis of ES‐SCLC.	2 L/3 L	Control	Placebo prior to topotecan	29	64 (47–82)	41.4	240 mg/m2	NR
				Experimental	Trilaciclib prior to topotecan	32	62 (47–77)	68.8
Daniel, 2021 [19]	Phase II RCT (Jun 2017—Feb 2018)	≥ 18 years, with confirmed ES‐SCLC.	1 L	Control	Placebo prior to E/C and atezolizumab	53	64 (46–83)	64.2	240 mg/m2	NR
				Experimental	Trilaciclib prior to E/C and atezolizumab	54	65 (45–81)	75.9
Cheng, 2022 [11]	Phase III RCT (May 2021–Dec 2022)	≥ 18 years, with histologically or cytologically diagnosed ES‐SCLC	1 L and 2 L/3 L	Control	Placebo before E/C or topotecan	42	60.5 (39–76)	83.3	240 mg/m2	14.4 months
				Experimental	Trilaciclib before E/C or topotecan	41	63 (45–77)	80.5		13.8 months
Elijah, 2024 [20]	Retrospective, cohort study (PEA: Feb 2020–Feb 2021 PEAT: Apr 2021–Jul 2022)	≥ 18 years, with confirmed ES‐SCLC	1 L	Control	Placebo prior to E/C ± atezolizumab	44	64 (49–84)	38.6	240 mg/m2	NR
				Experimental	Trilaciclib prior to E/C ± atezolizumab	34	69 (55–85)	64.7
Lenz, 2025 [12]	Phase III RCT (Jan 2021–Mar 2023)	≥ 18, histologically or cytologically confirmed pMMR/MSS mCRC	1 L	Control	Placebo prior to FOLFOXIRI/bevacizumab	147	55 (30–79)	61.9	240 mg/m2	NR
				Experimental	Trilaciclib prior to FOLFOXIRI/bevacizumab	149	58 (26–81)	63.1
Yan, 2025 [21]	Retrospective, cohort study (Jan 2022–Jan 2024)	≥ 18 years, with esophageal cancer who underwent concurrent radiotherapy	Definitive chemoradiotherapy/chemoradiotherapy+immunotherapy	Control	Placebo before chemoradiotherapy/chemoradiotherapy+immunotherapy (paclitaxel and nedaplatin+anti‐PD‐1 antibody)	34	< 65: 32.4%; ≥ 65: 67.6%	73.5	240 mg/m2	NR
				Experimental	Trilaciclib before chemoradiotherapy/chemoradiotherapy+immunotherapy	34	< 65: 23.5%; ≥ 65: 76.5%	76.5
He, 2025 [22]	Retrospective, cohort study (Jan 2020–Jan 2024)	≥ 18 years, histologically or cytologically confirmed ES‐SCLC	1 L	Control	Placebo before chemotherapy+immunotherapy Chemotherapy: E/C or E/P. Immunotherapy: durvalumab, toripalimab, tislelizumab, atezolizumab, and duvelumab	60	62	43.3	240 mg/m2	NR
				Experimental	Trilaciclib before chemotherapy+immunotherapy	60	63.5	53.3
Cui, 2025 [23]	Retrospective, cohort study (Jan 2020–Jan 2024)	≥ 18 years, histologically or cytologically confirmed ES‐SCLC	1 L	Control	Placebo before chemotherapy+immunotherapy Chemotherapy: E/C or E/P. Immunotherapy: surufilumab, tislelizumab, toripalimab, atezolizumab, durvalumab	90	61.5	62.2	240 mg/m2	NR
				Experimental	Trilaciclib before chemotherapy+immunotherapy	90	63.5	52.2

Abbreviations: 1L, first‐line; 2L, second‐line; 3L, third‐line; E/C, etoposide plus carboplatin; G/C, gemcitabine plus carboplatin; FOLFOXIRI, leucovorin/fluorouracil/oxaliplatin/irinotecan; E/P, etoposide plus cisplatin; NR, not reported.

The methodological quality of the included studies was generally high. The RCTs showed a low risk of bias across assessed domains (Figure S1), while the observational studies had MINORS scores ranging from 18 to 20 (Table S1). However, all observational studies lacked prospective data collection and unbiased assessment of study endpoints. In addition, Yan et al. [21] did not report a prospective study size calculation and Elijah et al. [20] did not use contemporary comparison groups, which may introduce potential bias.

3.2. Pooled Analysis of Clinical Response

3.2.1. Protective Effects on Neutrophil Lineage

Pooled analysis of 10 studies demonstrated that trilaciclib significantly reduced the risk of SN by 86% compared with controls (OR, 0.14; 95% CI, 0.06–0.31; p < 0.001; I² = 64.0%) (Figure 2A). Subgroup analysis showed that this reduction remained significant in patients with ES‐SCLC (OR, 0.11; 95% CI, 0.06–0.18; I² = 0%), whereas no significant effect was observed in other tumor types (Figure 2A).

FIGURE 2.

Forest plots comparing SN (A), FN (B), and DSN (C) between the experimental and control groups.

A similar reduction was observed for FN (OR, 0.19; 95% CI, 0.11–0.36; p < 0.001; I² = 0%) (Figure 2B). This effect was significant in both the ES‐SCLC subgroup (OR, 0.21; 95% CI, 0.11–0.42; I² = 0%) and other malignancies (OR, 0.12; 95% CI, 0.03–0.61; I² = 0%) (Figure 2B).

In addition, the DSN, assessed in 6 studies, was significantly shorter in the trilaciclib group (MD, −2.30 days; 95% CI, −4.28 to −0.31; p = 0.0309; I² = 87.5%) (Figure 2C). Subgroup analysis indicated that this reduction was significant in patients with ES‐SCLC (MD, −3.23 days; 95% CI, −5.12 to −1.33; I² = 62.6%), whereas no significant difference was observed in other tumor types (Figure 2C). A significant subgroup difference was also found for DSN (p = 0.0057, Figure 2C).

Subgroup analyses according to study design showed generally consistent results between RCTs and observational studies. Trilaciclib significantly reduced the incidence of SN and FN in both study types (Figure S2A,B).

3.2.2. Impact on Leukopenia and G‐CSF Support

Trilaciclib demonstrated a protective effect on overall white blood cell count. Across five studies, the incidence of Grade 3/4 leukopenia was significantly reduced (OR, 0.25; 95% CI, 0.13–0.46; p < 0.001; I² = 0%) (Figure 3A). Subgroup analysis showed that this reduction was significant in both the ES‐SCLC subgroup (OR, 0.18; 95% CI, 0.05–0.67; I² = 0%) and other malignancies (OR, 0.28; 95% CI, 0.14–0.56; I² = 16.6%) (Figure 3A).

FIGURE 3.

Forest plots comparing Grade 3/4 leukopenia (A) and G‐CSF (B) use between the experimental and control groups.

Analysis of nine studies further showed that the requirement for G‐CSF support was significantly lower in the trilaciclib group (OR, 0.36; 95% CI, 0.18–0.71; p = 0.0087; I² = 68.5%) (Figure 3B). This reduction was significant in the ES‐SCLC subgroup (OR, 0.30; 95% CI, 0.13–0.69; I² = 63.4%), but not in other tumor types (Figure 3B).

Similar reductions were observed for Grade 3/4 leukopenia in both study types (Figure S2C). In contrast, the reduction in G‐CSF use was statistically significant in observational studies but not in randomized trials, with no significant subgroup difference (Figure S2D).

3.2.3. Multi‐Lineage Protection: Red Blood Cell and Platelet Outcomes

Trilaciclib also showed protective effects on other hematopoietic lineages. For RBCs, analysis of 10 studies showed that the incidence of Grade 3/4 anemia was significantly lower (OR, 0.37; 95% CI, 0.27–0.52; p < 0.001; I² = 0%), leading to a corresponding decrease in the requirements for ESA (OR, 0.43; 95% CI, 0.22–0.81; p = 0.0093; I² = 0%) and RBC transfusions (OR, 0.39; 95% CI, 0.28–0.55; p < 0.001; I² = 0%). Similarly, for platelets, pooled results from seven studies demonstrated a significant decrease in Grade 3/4 thrombocytopenia (OR, 0.40; 95% CI, 0.27–0.60; p < 0.001; I² = 26.9%), which was accompanied by a reduction in platelet transfusion requirements (OR, 0.48; 95% CI, 0.30–0.76; p = 0.0017; I² = 17.3%). Corresponding results are shown in Figure S3.

3.2.4. Clinical Efficacy

To evaluate whether the myeloprotective effects of trilaciclib compromised antitumor activity, clinical efficacy outcomes were analyzed. Compared with the control group, trilaciclib was associated with a statistically significant improvement in OS (HR, 0.84; 95% CI, 0.71–0.99; p = 0.0373; I² = 49.5%). In contrast, no statistically significant differences were observed in PFS (HR, 0.88; 95% CI, 0.67–1.15; p = 0.3089; I² = 68.4%) or ORR (OR, 0.99; 95% CI, 0.76–1.29; p = 0.9422; I² = 44.8%) (Figure 4).

FIGURE 4.

Forest plots comparing OS (A), PFS (B), and ORR (C) between the experimental and control groups.

3.2.5. Other Treatment‐Related Adverse Events

The safety profile regarding non‐hematological toxicities was also assessed. Analysis of other treatment‐related adverse events, including nausea, vomiting, diarrhea, and fatigue, revealed no significant differences between the trilaciclib and control groups (Figure S4).

3.3. Sensitivity Analysis

Leave‐one‐out sensitivity analyses were conducted to assess the stability of the primary outcomes (Figure S5). Sequential exclusion of individual studies did not substantially alter the overall effect estimates for SN, FN, DSN, Grade 3/4 leukopenia, or G‐CSF use, indicating that the pooled results were generally robust. Specifically, exclusion of the pooled Tan 2019 [13] reduced heterogeneity in the SN analysis from 64.0% to 0%, with no substantial change in the pooled effect estimates.

4. Discussion

CIM is a common complication of cytotoxic chemotherapy, which increases the risk of infection and may lead to dose reductions or treatment delays [4]. In this meta‐analysis, trilaciclib administered prior to chemotherapy demonstrated significant myeloprotective effects. Overall, trilaciclib reduced neutropenia‐related events, decreased the need for supportive care interventions, and showed protective effects across multiple hematopoietic lineages without compromising antitumor efficacy. These findings are in line with previous clinical trials [9, 13]. In addition, the results of the sensitivity and subgroup analyses further supported the consistency of the main findings, although some heterogeneous outcomes should be interpreted with caution.

The protective effects of trilaciclib were especially evident in neutropenia‐related outcomes. Trilaciclib significantly reduced the incidence of SN and FN and shortened the DSN. Similarly, the incidence of Grade 3/4 leukopenia and the use of G‐CSF were both lower in the trilaciclib group. These protective effects are consistent with the known biological mechanism of trilaciclib. As a CDK4/6 inhibitor, trilaciclib transiently induces G1 cell cycle arrest in HSPCs prior to chemotherapy exposure, thereby reducing their susceptibility to cytotoxic injury and preserving multilineage hematopoietic function [8]. In addition, emerging evidence suggests that trilaciclib may also exert immune‐preserving or immunomodulatory effects. Preclinical models and translational analyses in patients with SCLC have shown that trilaciclib administered prior to chemotherapy may selectively preserve effector T cells, thereby promoting T cell activation and clonal expansion [24]. Similarly, exploratory immune profiling in patients with mTNBC has suggested that trilaciclib may modulate the tumor immune microenvironment by enhancing T cell effector function and reducing levels of immunosuppressive myeloid‐derived suppressor cells [25].

The reduction in DSN warrants further consideration. Although no universally accepted threshold defines a clinically meaningful reduction in DSN, the observed reduction of more than 2 days may still be clinically relevant, as a longer DSN may increase the risk of FN and infection‐related complications, which can contribute to hospitalization, mortality, increased healthcare burden, and chemotherapy dose reductions or delays [26]. However, the substantial heterogeneity observed for this outcome suggests that the DSN result should be interpreted cautiously. This may reflect differences in tumor types, chemotherapy regimens, baseline myelosuppression risk, study design, blood count monitoring schedules, and supportive care practices.

Beyond neutrophil‐related outcomes, our analysis also suggested that trilaciclib may provide broader protection across multiple hematopoietic lineages. Trilaciclib significantly reduced the incidence of Grade 3/4 anemia and was associated with lower use of ESAs and RBC transfusions. In addition, Grade 3/4 thrombocytopenia and platelet transfusion requirements were also reduced. These findings suggest that trilaciclib may provide broader protection against chemotherapy‐induced bone marrow suppression across multiple blood cell lineages. By reducing the incidence of cytopenias and the need for supportive interventions such as ESA and blood transfusions, trilaciclib may help alleviate the clinical burden of CIM and improve the overall tolerability of chemotherapy [5, 27].

Importantly, in our pooled analysis, trilaciclib was associated with a statistically significant improvement in OS, while no significant differences were observed in PFS or ORR. This apparent dissociation may be attributable to several confounding factors. First, the statistical significance of the OS benefit is marginal (p = 0.0373), with the 95% CI barely excluding unity. Consequently, these findings should be interpreted with considerable caution. Second, heterogeneity in post‐progression therapies—which were not consistently reported across the included studies—may have introduced bias, thereby confounding the OS estimates. Third, potential imbalances in baseline prognostic characteristics or differences in follow‐up duration among the studies could also contribute to this observation. Accordingly, these results warrant validation in prospective, rigorously controlled clinical trials. Nevertheless, these findings suggest that transient protection of HSPCs from chemotherapy‐induced damage does not interfere with the cytotoxic activity of chemotherapy against tumor cells. Similarly, analyses of non‐hematologic adverse events, including nausea, vomiting, diarrhea, and fatigue, showed no significant differences between the two groups, indicating that trilaciclib does not appear to increase the overall toxicity burden associated with chemotherapy.

Subgroup analyses suggested that trilaciclib may provide greater myeloprotective benefit in ES‐SCLC than in other tumor types. This finding is consistent with the FDA approval of trilaciclib, which was based on pivotal trials conducted in this population [7]. A possible explanation is that patients with ES‐SCLC are generally treated with highly myelosuppressive regimens, such as the platinum‐etoposide combination, and may therefore derive greater benefit from bone marrow protective strategies [28]. In addition, the currently available evidence for trilaciclib is predominantly derived from studies in ES‐SCLC, whereas studies in other tumor types have involved more heterogeneous patient populations and chemotherapy regimens, which may have contributed to the less consistent findings observed outside this subgroup [13, 20, 21, 22].

Our findings also extend those of the previous meta‐analysis by Qiu et al. [14]. While their analysis did not observe significant reductions in FN or platelet transfusion requirements, we observed significant decreases in both outcomes associated with trilaciclib use. This difference may be related to the larger evidence base included in our analysis, which increases the statistical power to detect treatment effects. Moreover, our subgroup analyses suggested that the myeloprotective effects of trilaciclib were particularly evident in ES‐SCLC, providing additional insight into the clinical contexts in which trilaciclib may offer the greatest benefit.

Several limitations of this study should be acknowledged. First, although this meta‐analysis included several solid tumor types, the available evidence was predominantly derived from ES‐SCLC, with relatively limited data from non‐ES‐SCLC tumors. Therefore, the findings are most applicable to ES‐SCLC, while evidence in other tumor types should be interpreted with caution and requires further confirmation. Second, publication bias was not formally assessed because the number of studies included in most outcomes was relatively small, which limited the reliability and statistical power of funnel plot asymmetry tests and Egger's regression test. Therefore, the possibility of publication bias, including the potential influence of unpublished negative studies, could not be excluded and should be considered when interpreting the findings, as it may have led to an overestimation of the observed effect sizes. Third, moderate‐to‐high heterogeneity was observed in some outcomes, likely reflecting differences in tumor types, chemotherapy regimens, study designs, and patient populations across the included studies. Fourth, although the inclusion of observational studies broadened the evidence base and increased statistical power, it may also have introduced biases inherent to observational research, such as residual confounding, treatment selection bias, and institutional differences in supportive care practices. However, the overall direction of effect remained generally consistent across subgroup and sensitivity analyses, suggesting that the main findings were relatively stable.

5. Conclusions

In conclusion, trilaciclib significantly reduced CIM and the subsequent need for supportive care interventions, with a possible OS benefit and no apparent compromise in PFS or ORR. The evidence is most consistent in ES‐SCLC, with only preliminary data available for other solid tumors. Further large‐scale trials are warranted to define its role across diverse tumor types and treatment settings.

Author Contributions

Wei Tian: conceptualization, methodology, formal analysis, data curation, visualization, writing – original draft. Qianxin Liu: data curation, validation, writing – review and editing. Ying Zhou: supervision, conceptualization, writing – review and editing. Zhuo Zhang: supervision, methodology, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Figure S1: Risk of bias summary of the included RCTs.

Figure S2: Subgroup analysis of SN (A), FN (B), Grade 3/4 leukopenia (C), and G‐CSF use (D) by study design.

Figure S3: Forest plots comparing Grade 3/4 anemia (A), ESA use (B), RBC transfusion (C), Grade 3/4 thrombocytopenia (D), and platelet transfusion (E) between the experimental and control groups.

Figure S4: Forest plots comparing nausea (A), vomiting (B), diarrhea (C), and fatigue (D) between the experimental and control groups.

Figure S5: Leave‐one‐out sensitivity analysis for SN (A), FN (B), DSN (C), Grade 3/4 leukopenia (D) and G‐CSF use (E).

Table S1: The revised and validated version of MINORS.

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.