Please provide key clinical trials supporting Cosela, particularly the efficacy and safety data; please include details on study design, patient population, primary and secondary endpoints, efficacy outcomes, and the incidence of clinically relevant adverse events.

Comment by InpharmD Researcher

Please see Tables 1-4 for summary tables of the requested clinical trials assessing the efficacy and safety of Cosela (trilaciclib). Across clinical trials, trilaciclib consistently demonstrated significant reductions in chemotherapy-induced myelosuppression without detriment to antitumor efficacy, and was generally well tolerated with a favorable safety profile compared to placebo. However, its use is limited to a narrow patient population, requires intravenous administration prior to chemotherapy, and should be weighed against acquisition costs and institutional supportive care practices.
Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

Please provide key clinical trials supporting Cosela, particularly the efficacy and safety data; please include details on study design, patient population, primary and secondary endpoints, efficacy outcomes, and the incidence of clinically relevant adverse events.

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Tables 1-4 for your response.

Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial
Design

Phase Ib (open-label, dose-finding) and phase II (randomized, double-blind placebo-controlled) multicenter, proof-of-concept study in North America and Europe

N=122
Objective To assess the ability of trilaciclib to reduce chemotherapy-induced myelosuppression and improve safety across multiple hematopoietic lineages
Study Groups

Part 1:

  • Cohort 1 (E/P + trilaciclib 200 mg/m2) (n=10)
  • Cohort 2 (E/P + trilaciclib 240 mg/m2) (n=9)

Part 2:

  • E/P + placebo (n=38)
  • E/P + trilaciclib 240 mg/m2 (n=39)
Inclusion Criteria Patients ≥18 years of age, with histologically or cytologically confirmed extensive-stage small cell lung cancer (SCLC), measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, and adequate organ function

Exclusion Criteria

(from study protocol)

Prior chemotherapy for limited- or extensive-stage SCLC; symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids; history of other malignancies (except adequately treated basal/squamous cell skin carcinoma, curatively treated in-situ cervical carcinoma, prostate cancer, or superficial bladder cancer, or other curatively treated solid tumors with no evidence of disease for ≥3 years); uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure; known history of stroke or cerebrovascular accident within 6 months of enrollment; serious active infection; psychiatric illness that would limit study participation
Methods

Part 1 of the study included a phase Ib, open-label, dose-finding portion followed by a phase IIa, open-label, expansion at the recommended phase II dose (RP2D). Part 2 was a double-blind, placebo-controlled phase II with patients randomized 1:1 to receive chemotherapy plus trilaciclib or placebo and stratified by ECOG performance status (0–1 versus 2).

Patients received trilaciclib or placebo before etoposide/carboplatin (E/P) on days 1–3 of each cycle. Trilaciclib was administered intravenously at 200 mg/m2 or 240 mg/m2. Carboplatin was dosed at area-under-the-curve (AUC) 5 on day 1 and etoposide at 100 mg/m2 on days 1–3. Dose modifications were allowed for chemotherapy but not for trilaciclib. Growth factors were administered per American Society for Clinical Oncology (ASCO) guidelines.
Duration Not specified
Outcome Measures

Primary: Safety and tolerability of trilaciclib with E/P

Secondary: Reduction in chemotherapy-induced myelosuppression, antitumor efficacy [measured as overall response rate (ORR), progression-free survival (PFS), and overall survival (OS)]
Baseline Characteristics   Part 1

Part 2
 

Cohort 1 (E/P+trilaciclib 200 mg/m2)

(N=10)

Cohort 2 (E/P+trilaciclib 240 mg/m2)

(N=9)

E/P+placebo

(N=38)

E/P+trilaciclib 240 mg/m2

(N=39)

Total

(N=77)
Age, years (Mean ± SD) 70 ± 11.6 62 ± 8.6 65 ± 9.5 65 ± 8.4 65 ± 8.9
Age group <65, n (%) 2 (20.0%) 5 (55.6%) 17 (44.7%) 20 (51.3%) 37 (48.1%)
Age group ≥65, n (%) 8 (80.0%) 4 (44.4%) 21 (55.3%) 19 (48.7%) 40 (51.9%)
Sex - Male, n (%) 4 (40.0%) 7 (77.8%) 27 (71.1%) 27 (69.2%) 54 (70.1%)
ECOG score 0-1, n (%) N/A N/A 35 (92.1%) 35 (89.7% 70 (90.9%)
ECOG score 2, n (%) N/A N/A 3 (7.9%) 4 (10.3%) 7 (9.1%)
Results  

E/P+placebo

(n=38)

E/P+trilaciclib 240 mg/m2

(n=39)

 p-value
Occurrence of severe neutropenia, n (%) 16 (43.2%) 2 (5.3%) 0.0001
Mean duration of severe neutropenia (days) 3 (3.9) 0 (0.5) 0.0003
ORR (%) 56.8% 66.7% 0.3831
Median PFS (months) 5.0 6.2 0.1695
Median OS (months) 10.6 10.9 0.6107
Adverse Events Fewer grade 3 adverse events in trilaciclib group (50%) compared to placebo (83.8%), primarily due to less hematological toxicity. No trilaciclib-related grade 3 adverse events occurred.
Study Author Conclusions Trilaciclib demonstrated an improvement in the patient’s tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy. These data demonstrate strong proof-of-concept for trilaciclib’s myelopreservation benefits.
Critique The study provides strong evidence for trilaciclib's myelopreservation benefits, improving safety without compromising efficacy. However, as an exploratory study, it may lack statistical power for some endpoints. The study's design and execution were robust, but the lack of detailed exclusion criteria and the potential for selection bias in patient demographics could limit generalizability.
Table 1 References:
[1] Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019;30(10):1613-1621. doi:10.1093/annonc/mdz278

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
Design

International, multicenter, randomized, double-blind, placebo-controlled Phase II trial

N= 107
Objective To evaluate the myelopreservation efficacy of trilaciclib vs placebo when administered prior to myelosuppressive chemotherapy plus atezolizumab
Study Groups

Trilaciclib group (n= 54)

Placebo group (n= 53)
Inclusion Criteria Adults ≥18 years of age with confirmed extensive-stage small cell lung cancer (ES-SCLC), an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Exclusion Criteria Patients with symptomatic brain metastases or who had received prior systemic therapy for limited-stage or ES-SCLC
Methods Patients were treated in an induction phase and a maintenance phase. Patients were randomized 1:1 to receive trilaciclib or placebo prior to etoposide/carboplatin/atezolizumab (E/P/A) therapy. Trilaciclib (240 mg/m2) or placebo was administered as a 30-minute intravenous (IV) infusion on D1, D2, and D3 prior to E/P/A therapy. Etoposide (100 mg/m2) was administered on D1, D2, and D3, and carboplatin (area-under-the-curve [AUC] 5; max dose 750 mg) on D1, both via IV infusion. Atezolizumab (1200 mg) was administered on D1 by IV infusion following E/P administration.
Duration June 29, 2017 to February 9, 2018
Outcome Measures

Primary: Duration of severe neutropenia (DSN) in Cycle 1 (defined as absolute neutrophil count <0.5 x 106 cells/L), occurrence of severe neutropenia (SN) during the treatment period

Secondary: Occurrence of red blood cell (RBC) transfusions on or after Week 5, occurrence of granulocyte colony-stimulating factor (G-CSF) administrations, total number of all-cause chemotherapy dose reductions
Baseline Characteristics  

Trilaciclib prior to E/P/A

(n= 54)

Placebo prior to E/P/A

(n= 53)
Median age (range), years  65 (45-81) 64 (46-83)
Male, n (%) 41 (75.9%) 34 (64.2%)
White race, n (%) 53 (98.1%) 51 (96.2%)
ECOG PS 0-1, n (%) 45 (85.2%) 46 (86.8%)
Brain metastases, n (%) 15 (27.8%) 15 (28.3%)
Results  

Trilaciclib prior to E/P/A

(n= 54)

Placebo prior to E/P/A

(n= 53)

 p-value
Mean duration (days) of grade 4 SN in Cycle 1 0 4.0 <0.0001
Patients with grade 4 SN 1.9% 49.1% <0.0001
Patients with febrile neutropenia adverse events 1.9% 5.7% 0.3105
Patients with G-CSF administration 29.6% 47.2% 0.0686
Patients with RBC transfusion ≥ week 5 13.0% 20.8% 0.1335
Adverse Events Trilaciclib was well tolerated, with fewer grade ≥3 AEs vs placebo, primarily due to less high-grade hematological toxicity. Common adverse events included fatigue, nausea, and anemia. 
Study Author Conclusions Compared with placebo, trilaciclib administered prior to E/P/A improved patients' experience of receiving treatment for ES-SCLC, as shown by reducing myelosuppression, and improved HRQoL and safety profiles.
Critique The study demonstrated significant myelopreservation benefits and improved HRQoL with trilaciclib, but the small sample size may limit the ability to detect significant differences in secondary endpoints and antitumour efficacy. Further research is needed to explore the potential immune-enhancing effects of trilaciclib in more immunogenic tumour types.
Table 2 References:
[2] 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. 2021;148(10):2557-2570. doi:10.1002/ijc.33453

Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study
Design

International, multicenter, randomized, double-blind, placebo-controlled phase II trial

N= 61
Objective To evaluate the myelopreservation effects of trilaciclib administered prior to topotecan in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC)
Study Groups

Trilaciclib (n= 32)

Placebo (n= 29)
Inclusion Criteria Adults aged ≥18 years with confirmed diagnosis of ES-SCLC, disease progression during or after first- or second-line chemotherapy, eligible to receive topotecan, with ≥1 measurable target lesion per Response Evaluable Criteria in Solid Tumors (RECIST) v1.1, adequate organ function, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
Exclusion Criteria History of topotecan treatment for SCLC or brain metastases requiring immediate treatment
Methods

Patients were randomized to receive trilaciclib 240 mg/m2 or placebo as a 30-minute intravenous (IV) infusion ≤4 hours before topotecan 1.5 mg/m2 on days 1–5 of each 21-day cycle. Randomization was stratified based on ECOG PS (0/1 vs 2) and sensitivity to first-line treatment. Patients were treated until progression, unacceptable toxicity, withdrawal of consent, or discontinuation by the patient or investigator. No dose modifications of trilaciclib were allowed. Topotecan dose reductions were only allowed twice for any patient and were permanent. Supportive care measures were allowed after cycle 1 per guidelines. Additional endpoints included myelopreservation, safety, patient-reported outcomes (PROs), and antitumor efficacy. 
Duration

Data cut-off for myelopreservation and patient-reported outcome (PRO) analyses: September 28, 2018

Data cut-off for safety, hospitalization, and antitumor endpoint analyses: May 31, 2019
Outcome Measures

Primary: Duration of severe neutropenia (DSN) in cycle 1, occurrence of severe neutropenia (SN, absolute neutrophil count <0.5 x 109 cells/L)

Secondary: Occurrence of red blood cell (RBC) transfusions on/after week 5, granulocyte colony-stimulating factor (G-CSF) administration, platelet transfusions, all-cause dose reductions
Baseline Characteristics  

Trilaciclib prior to topotecan 1.5 mg/m2

(n = 32)

Placebo prior to topotecan 1.5 mg/m2

(n = 29)

  
Age, median, (min, max) years 62 (47, 77) 64 (47, 82)  
Age group, n (%) - 18– < 65 years 20 (62.5) 18 (62.1)  
Age group, n (%) - ≥ 65 years 12 (37.5) 11 (37.9)  
Gender, n (%) - Male 22 (68.8) 12 (41.4)  
ECOG PS, n (%) - 0/1 29 (90.6) 27 (93.1)  
ECOG PS, n (%) - 2 3 (9.4) 2 (6.9)  
Smoking history, n (%) - Never 3 (9.4) 2 (6.9)  
Smoking history, n (%) - Former 16 (50.0) 20 (69.0)  
Smoking history, n (%) - Current 13 (40.6) 7 (24.1)  
Treatment line, n (%) - Second 26 (81.2) 24 (82.8)  
Treatment line, n (%) - Third 6 (18.8) 5 (17.2)  
Sensitivity to first-line treatment, n (%) - Sensitive 14 (43.8) 13 (44.8)  
Sensitivity to first-line treatment, n (%) - Resistant 18 (56.3) 16 (55.2)  
Brain metastases at baseline, n (%) 8 (25.0) 5 (17.2)  
Weight loss ≥ 6 months prior to randomization, n (%) - No 22 (68.8) 21 (72.4)  
Weight loss ≥ 6 months prior to randomization, n (%) - Yes 10 (31.3) 8 (27.6)  
Results  

Trilaciclib prior to topotecan

(n = 32)

Placebo prior to topotecan

(n = 29)

p-value
Mean DSN in cycle 1, days 2 7 <0.0001
Patients with SN, % 40.6 75.9 0.016
Patients with G-CSF administration, % 50.0 65.5 -
Patients with febrile neutropenia event, % 6.3 17.2 -
Patients with RBC transfusions on/after week 5, % 31.3 41.4 -
Patients with platelet transfusions, % 25.0 31.0 -
Patients with all-cause dose reduction, % 18.8 31.0 -
Patients with infection serious adverse events (SAEs), % 3.1 10.3 -
Patients with pulmonary infection SAEs, % 3.1 3.4 -
Adverse Events Fewer grade ≥3 hematologic adverse events in trilaciclib group, particularly neutropenia (75.0% vs. 85.7%) and anemia (28.1% vs. 60.7%). Common adverse events included neutropenia, thrombocytopenia, anemia, fatigue, and nausea. Grade 3 or 4 febrile neutropenia events were lower in trilaciclib group (6.3% vs. 17.9%)
Study Author Conclusions Compared with placebo, the addition of trilaciclib prior to topotecan for the treatment of patients with previously treated ES-SCLC improves the patient experience of receiving chemotherapy, as demonstrated by a reduction in chemotherapy-induced myelosuppression, improved safety profile, improved quality of life and no detrimental effects of antitumor efficacy.
Critique The study demonstrated significant myelopreservation benefits and improved patient-reported outcomes, but the small sample size may limit the detection of differences in overall survival. The imbalance in prognostic factors between treatment arms could have influenced survival outcomes. Further studies are needed to explore the effects of trilaciclib in larger populations and different chemotherapy settings.
Table 3 References:
[3] Hart LL, Ferrarotto R, Andric ZG, et al. Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021;38(1):350-365. doi:10.1007/s12325-020-01538-0

Myeloprotection with trilaciclib in Chinese patients with extensive-stage small cell lung cancer receiving chemotherapy: Results from a randomized, double-blind, placebo-controlled phase III study (TRACES)
Design

Multicenter, randomized, double-blind, placebo-controlled phase III study in China

N= 95
Objective To assess the safety, efficacy, and pharmacokinetics (PK) of trilaciclib before chemotherapy in Chinese patients with extensive-stage small cell lung cancer (ES-SCLC)
Study Groups

Trilaciclib (n= 41)

Placebo (n= 42)
Inclusion Criteria Male or female aged ≥18 years old, with histologically or cytologically diagnosed ES-SCLC, ≥1 measurable lesion without radiotherapy as per Response Evaluable Criteria in Solid Tumors (RECIST) v1.1 criteria, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0–2, and adequate organ function
Exclusion Criteria Previously treated patients having prior exposure to topotecan were excluded because patients were treated with topotecan during the study
Methods The study included an open-label safety run-in part (Part 1) and a double-blinded, placebo-controlled part (Part 2). Patients received intravenous trilaciclib (240 mg/m2) or placebo before etoposide/carboplatin or topotecan. Primary endpoints were PK, safety, and duration of severe neutropenia (DSN) in Cycle 1. Exploratory endpoints included other myeloprotection endpoints, safety, and antitumor efficacy.
Duration May 2021 to December 2022
Outcome Measures

Primary: PK, safety and duration of severe neutropenia (DSN) in Cycle 1

Secondary: Occurrence of severe neutropenia (SN), red blood cell (RBC) transfusion, granulocyte colony-stimulating factor (G-CSF) administration, Grade 3/4 hematological toxicities
Baseline Characteristics  

Part 1

(N = 12)

Part 2

(N = 83)
Age, median years (range) 61.0 (51–73) 62.0 (39–77)
Male sex, n (%) 9 (75.0%) 68 (81.9%)
ECOG PS 0–1, n (%) 12 (100%) 79 (95.2%)
Treatment line, first, n (%) 5 (50%) 46 (55.4%)
Treatment line, second/third, n (%) 5 (50%) 37 (44.6%)
Brain metastases at baseline, n (%) 5 (41.7%) 29 (34.9%)
Results  

Trilaciclib

(n= 41)

Placebo

(n= 42)

 p-value or adjusted rate ratio (aRR) (95% CI)
DSN in Cycle 1, mean (SD) 0 (1.7) 2 (3.0) 0.0003
SN occurrence rate 9.8% 47.6% aRR 0.188 (95 % CI 0.069 to 0.513)
G-CSF use rate (per cycle) 0.323 0.503 aRR 0.563 [95 % CI:0.402, 0.788])

A similar trend for improved RBC endpoints favoring trilaci clib was observed, including a reduction in the incidence of Grade 3/4 anemia and percentage of patients receiving erythropoietin stimulating agents (ESAs).

After a median follow-up of 14.1 months, the median overall survival was 12.0 months in trilaciclib arm and 8.8 months in placebo arm (HR, 0.69; 95 % CI: 0.40-1.22). Median progression-free survival was 4.8 months and 4.3 months, respectively (HR, 0.86; 95 % CI: 0.53-1.39).
Adverse Events All patients experienced at least one treatment-emergent adverse event (TEAE). Grade ≥3 TEAEs were less frequent in the trilaciclib arm (68.3% vs 88.1%). Serious AEs attributed to study drug were observed at similar rates between groups. Fewer patients in the trilaciclib arm discontinued study drug due to TEAEs (2.4% vs 7.1%).
Study Author Conclusions Trilaciclib in the Chinese population demonstrated a similar PK and safety profile as seen in other global trials. There was a significant reduction of DSN in Cycle 1, thereby substantiating the myeloprotective effects of trilaciclib in Chinese ES-SCLC patients.
Critique The study confirms the efficacy of trilaciclib in reducing chemotherapy-induced myelosuppression in Chinese patients, consistent with global data. However, the sample size was not large enough to detect meaningful differences in antitumor efficacy endpoints. Future studies with larger sample sizes are needed to explore the antitumor effects of trilaciclib in ES-SCLC.
Table 4 References:
[4] Cheng Y, Wu L, Huang D, et al. Myeloprotection with trilaciclib in Chinese patients with extensive-stage small cell lung cancer receiving chemotherapy: Results from a randomized, double-blind, placebo-controlled phase III study (TRACES). Lung Cancer. 2024;188:107455. doi:10.1016/j.lungcan.2023.107455