Dataset Information

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.

ABSTRACT: Trilaciclib is an intravenous CDK4/6 inhibitor administered prior to chemotherapy to preserve haematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myelopreservation). The effects of administering trilaciclib prior to carboplatin, etoposide and atezolizumab (E/P/A) were evaluated in a randomised, double-blind, placebo-controlled Phase II study in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) (NCT03041311). The primary endpoints were duration of severe neutropenia (SN; defined as absolute neutrophil count <0.5 × 10⁹ cells per L) in Cycle 1 and occurrence of SN during the treatment period. Other endpoints were prespecified to assess the effects of trilaciclib on additional measures of myelopreservation, patient-reported outcomes, antitumour efficacy and safety. Fifty-two patients received trilaciclib prior to E/P/A and 53 patients received placebo. Compared to placebo, administration of trilaciclib resulted in statistically significant decreases in the mean duration of SN in Cycle 1 (0 vs 4 days; P < .0001) and occurrence of SN (1.9% vs 49.1%; P < .0001), with additional improvements in red blood cell and platelet measures and health-related quality of life (HRQoL). Trilaciclib was well tolerated, with fewer grade ≥3 adverse events compared with placebo, primarily due to less high-grade haematological toxicity. Antitumour efficacy outcomes were comparable. Administration of trilaciclib vs placebo generated more newly expanded peripheral T-cell clones (P = .019), with significantly greater expansion among patients with an antitumour response to E/P/A (P = .002). Compared with placebo, trilaciclib administered prior to E/P/A improved patients' experience of receiving treatment for ES-SCLC, as shown by reduced myelosuppression, and improved HRQoL and safety profiles.

SUBMITTER: Daniel D

PROVIDER: S-EPMC8048941 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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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.

Daniel Davey D Kuchava Vladimer V Bondarenko Igor I Ivashchuk Oleksandr O Reddy Sreekanth S Jaal Jana J Kudaba Iveta I Hart Lowell L Matitashvili Amiran A Pritchett Yili Y Morris Shannon R SR Sorrentino Jessica A JA Antal Joyce M JM Goldschmidt Jerome J

International journal of cancer 20210112 10

Trilaciclib is an intravenous CDK4/6 inhibitor administered prior to chemotherapy to preserve haematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myelopreservation). The effects of administering trilaciclib prior to carboplatin, etoposide and atezolizumab (E/P/A) were evaluated in a randomised, double-blind, placebo-controlled Phase II study in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) (NCT03041311). The prima ...[more]

PMID: 33348420

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Project description:BackgroundTrilaciclib, an intravenous short acting cyclin-dependent kinase 4/6 inhibitor, has been approved for the prevention of chemotherapy-induced myelosuppression (CIM) in patients with extensive stage small cell lung cancer (ES-SCLC) receiving platinum/etoposide (EP) or topotecan (TPT)-based therapy in United States (US) since February 2021. Trilaciclib use received the priority review and approval in a real-world setting in China. This study thus aimed to collect real-world data and evaluate the protective effect of trilaciclib on CIM in Chinese patients with ES-SCLC.MethodsThis single-arm, noninterventional real world study invited all patients with ES-SCLC who received trilaciclib with the platinum and etoposide ± anti-programmed cell death ligand-1 [anti-PD-(L)1] antibodies (EP group) or trilaciclib with TPT (TPT group) in Boao, Hainan China to participate in the study. The primary endpoint was the incidence of the severe (grade four) neutropenia (SN), and the secondary endpoints included other myeloprotection effects, safety and anti-tumor activity.ResultsBetween August 2021 and December 2022, a total of 30 patients who received trilaciclib with chemotherapy consented to participate in this real-world study. Among the enrolled patients, 26 patients were treated with EP regimen, of these, 18 patients were combined with anti-PD-(L)1 antibodies, and 4 patients were treated with TPT. The incidence of SN was 6.7%, with one patient each in EP group and TPT group. The incidence of grade three hematological toxicities was 30% (9/30), with 19.2% (5/26) in the EP group, and 100% (4/4) in the TPT group. The incidence of grade four hematological toxicities was 5/30 (16.7%), with 3/26 (11.5%) and 2/4 (50%) in EP and TPT group, respectively. Overall, the incidence of those who received intravenous or oral antibiotics was 6/30 (20%), with 4/26 (15.4%) in the EP group, and 2/4 (50%) in the TPT group. No ≥ grade three adverse events, serious adverse events (SAEs), and adverse events of special interest associated with trilaciclib were reported.ConclusionsTrilaciclib decreased the incidence of CIM in Chinese patients when administered prior to an EP-containing regimen [combined with or without PD-(L)1] or TPT for ES-SCLC. The effect of myeloprotection, anti-tumor and safety were all consistent with the studies conducted globally and data from the Chinese Phase three placebo-controlled study (TRACES).

Dataset Information

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.

Publications

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.

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