TY - JOUR
T1 - Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer
T2 - A multicentre, randomised, double-blind, placebo-controlled Phase II trial
AU - Daniel, Davey
AU - Kuchava, Vladimer
AU - Bondarenko, Igor
AU - Ivashchuk, Oleksandr
AU - Reddy, Sreekanth
AU - Jaal, Jana
AU - Kudaba, Iveta
AU - Hart, Lowell
AU - Matitashvili, Amiran
AU - Pritchett, Yili
AU - Morris, Shannon R.
AU - Sorrentino, Jessica A.
AU - Antal, Joyce M.
AU - Goldschmidt, Jerome
N1 - Funding Information:
We thank and acknowledge all the patients, their families and study personnel for participating in the study. We thank Jie Xiao (G1 Therapeutics, Inc) for her statistical support, Ruhi Rai (G1 Therapeutics, Inc) for her bioinformatics support, and Barbara Banbury, Julie Rytlewski and Marissa Vignali (Adaptive Biotechnologies) for their support with the immunosequencing analyses. Our study was funded by G1 Therapeutics, Inc. Data were collected by the investigators, analysed by G1 Therapeutics, Inc, Covance Central Laboratory Services, Inc (for flow cytometry data; Geneva, Switzerland and Indianapolis, US), Fios Genomics Ltd (for bioinformatic analysis; Edinburgh, UK), Epistem, Ltd (for PD‐L1 immunohistochemistry data; Manchester, UK) and Adaptive Biotechnologies (for immunosequencing data; Seattle, US) and interpreted by authors. Medical writing assistance was provided by Beth Demetrious‐Seymour of Alligent Europe (Envision Pharma Group), funded by G1 Therapeutics, Inc.
Funding Information:
Dr Davey Daniel has received research funding from G1 Therapeutics, Inc and Genentech. Dr Jana Jaal has received research funding from AstraZeneca, and has been an adviser to AstraZeneca, Boehringer Ingelheim and MSD. Dr Lowell Hart has received research funding, consultancy and travel expenses from G1 Therapeutics, Inc. Dr Yili Pritchett and Dr Jessica A. Sorrentino are paid employees and shareowners of G1 Therapeutics, Inc. Dr Shannon R. Morris and Joyce M. Antal were employees of G1 Therapeutics, Inc at the time of manuscript preparation and submission. Dr Vladimer Kuchava, Prof. Igor Bondarenko, Dr Oleksandr Ivashchuk, Dr Sreekanth Reddy, Dr Iveta Kudaba and Dr Amiran Matitashvili have no conflicts of interest to declare. Dr Jerome Goldschmidt has participated in speakers bureau and received honoraria from Amgen and Bristol Myers Squibb.
Publisher Copyright:
2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/15
Y1 - 2021/5/15
N2 - 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.
AB - 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.
KW - chemotherapy
KW - myelopreservation
KW - myelosuppression
KW - small cell lung cancer (SCLC)
KW - trilaciclib
UR - http://www.scopus.com/inward/record.url?scp=85099198905&partnerID=8YFLogxK
U2 - 10.1002/ijc.33453
DO - 10.1002/ijc.33453
M3 - Article
C2 - 33348420
AN - SCOPUS:85099198905
SN - 0020-7136
VL - 148
SP - 2557
EP - 2570
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 10
ER -