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Trilaciclib (T) decreases myelosuppression in extensive-stage small cell lung cancer (ES-SCLC) patients receiving first-line chemotherapy plus atezolizumab

2019; Elsevier BV; Volume: 30; Linguagem: Inglês

10.1093/annonc/mdz264.006

1569-8041

D. B. Daniel, Vladimer Kuchava, Igor Bondarenko, О. І. Іващук, David R. Spigel, Abhijit Dasgupta, Sashidhar Reddy, Tamar Melkadze, Jana Jaal, Iveta Kudaba, L. Hart, Amiran Matitashvili, Krassimir Koynov, Zhihao Yang, Steven G. Wolfe, R. K. Malik, Shannon R. Morris, J.M. Antal, Jerome H. Goldschmidt,

Cancer therapeutics and mechanisms

Abstract Background Chemotherapy (chemo)-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Current supportive therapies are lineage specific and administered after damage has occurred. T, a highly selective, reversible CDK4/6 inhibitor and first-in-class myelopreservation agent, preserves HSPCs during chemotherapy, improving its safety and tolerability. This trial (NCT03041311) studied the benefits of T in ES-SCLC patients receiving 1L chemo + atezolizumab (A). Methods This placebo (P)-controlled, double-blind, Ph2 study randomized (1:1) chemo-naive ES-SCLC pts with adequate organ function, ECOG 0-2, and no symptomatic brain mets, to T or P with etoposide/carboplatin/A (ECA) for four induction cycles followed by maintenance (A). Prophylactic growth factors were prohibited in cycle 1; otherwise standard supportive care was allowed. Prespecified lineage-specific endpoints assessed the effect of T on myelosuppression. Tumor response was assessed using RECIST v1.1. FACT-L and FACT-An were evaluated. Results T + ECA was well tolerated with fewer ≥ G3 AEs in T (62% overall; 50% any drug related) vs P (87%; 74%), primarily due to less heme toxicity. T improved ANC, RBC measures and SOC interventions (Table). T also delayed time to deterioration in some PRO functioning domains and anemia symptoms. T did not affect chemo efficacy as measured by ORR and PFS; OS will be presented. Table: 1742PD . Parameter, n [1] ECA + P N = 53 ECA + T N = 54 Adjusted 1-sided P- value Mean Duration (d) G4 ANC in Cycle 1[2] 4 0 Pts w G4 ANC* 26 (49%) 1 (2%) Dose reductions (per 100 cycles) ǂ 8.5 2.1 0.0195 Pts w RBC transfusions ≥ week 5* 11 (21%) 7 (13%) 0.1335 Pts w G-CSF Admin* 25 (47%) 16 (30%) 0.0686 [1] Data presented as proportion (*) or event rate (ǂ) [2] Surrogate for febrile neutropenia Conclusions Addition of T improves safety/tolerability of chemo as shown by statistically significant and clinically meaningful improvement in myelosuppression endpoints, reduction of chemo side effects, and SOC interventions and no detriment to anti-tumor efficacy. These data confirm the myelopreservation benefits of T seen in another 1L ES-SCLC trial (NCT02499770). Clinical trial identification GIT28-05: NCT03041311, EudraCT2017-000358-20. Legal entity responsible for the study G1 Therapeutics, Inc. Funding G1 Therapeutics, Inc. Disclosure D. Daniel: Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): ER Squibb & sons; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingleheim; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Eli Lilly and Company; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Roche. D. Spigel: Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): G1 Therapeutics. J. Jaal: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. L. Hart: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: G1 Therapeutics. K.D. Koynov: Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): servier; Honoraria (institution): Novartis; Honoraria (institution): Merck; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: MSD; Honoraria (institution): Bayer; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Astelas; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (institution): Intellect Pharma; Travel / Accommodation / Expenses: AstraZeneca. Z.(. Yang: Full / Part-time employment: G1 Therapeutics. S.G. Wolfe: Full / Part-time employment: G1 Therapeutics. R. Malik: Full / Part-time employment: G1 Therapeutics. S.R. Morris: Full / Part-time employment: G1 Therapeutics. J.M. Antal: Full / Part-time employment: G1 Therapeutics. All other authors have declared no conflicts of interest.