Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy‐induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials

Abstract

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LP2, a stable lanthipeptide derived from cAng‐(1‐7), exerts myeloprotective action in mice

“…Trilaciclib induces a transient, reversible G1 cell cycle arrest of proliferating hematopoietic stem and progenitor cells in bone marrow, thus protecting them from damage during chemotherapy. Its myeloprotection has been demonstrated in clinical studies for small cell lung cancer 20–22 . Trilaciclib effectively protects against neutropenia 21 and enhances the antitumor activity of chemotherapy and immune checkpoint inhibitor combinations 23 .…”

Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of malignant pleural mesotheliomas to CDK4/6 inhibition

“…Interestingly, in tumors predicted to be insensitive to CDK4/6i, transient administration of these drugs could be used to transiently arrest proliferation of normal cells and prevent chemotherapy-induced myelosuppression, hence allowing to increase the dose of genotoxic drugs such as cisplatin and thus the therapeutic window between normal and transformed cells (96). This idea has been validated clinically in small cell lung cancers that are generally insensitive to CDK4/6i due to their RB1 locus alteration (97), leading to recent approval by the FDA of trilaciclib for this indication. Therefore, defining or predicting the CDK4 phosphorylation status might really be one key to tailor the use of CDK4/6i in MPM treatment and their combination with targeted or genotoxic therapies.…”

Population pharmacokinetics and exposure–response of trilaciclib in extensive‐stage small cell lung cancer and triple‐negative breast cancer

“…14,16,19,20 Administration of trilaciclib prior to chemotherapy also improved multiple other myelosuppression endpoints, including the incidence of grade 3/4 haematologic adverse events (AEs), and resulted in the need for fewer supportive care interventions, fewer dose modifications and improved quality of life. 14,16,[19][20][21] Antitumour efficacy outcomes were comparable in the trilaciclib and placebo arms, indicating that, while administration of trilaciclib prior to chemotherapy did not enhance antitumour efficacy in the setting of ES-SCLC, neither did it antagonize the intended effects of chemotherapy. 14,16,19 The recommended phase 2 dose (RP2D) and approved dose for trilaciclib in patients with ES-SCLC is 240 mg/m 2 , as established by analysis of integrated pharmacokinetic (PK), pharmacodynamic (PD),…”

“…In each individual trial and in a pooled analysis of all three trials, the addition of trilaciclib prior to standard chemotherapy significantly improved the primary endpoints of duration of severe neutropenia in cycle 1 and occurrence of severe neutropenia 14,16,19,20 . Administration of trilaciclib prior to chemotherapy also improved multiple other myelosuppression endpoints, including the incidence of grade 3/4 haematologic adverse events (AEs), and resulted in the need for fewer supportive care interventions, fewer dose modifications and improved quality of life 14,16,19–21 . Antitumour efficacy outcomes were comparable in the trilaciclib and placebo arms, indicating that, while administration of trilaciclib prior to chemotherapy did not enhance antitumour efficacy in the setting of ES‐SCLC, neither did it antagonize the intended effects of chemotherapy 14,16,19 …”