Effect of trilaciclib, a CDK 4/6 inhibitor, on myelosuppression in patients with previously treated extensive-stage small cell lung cancer receiving topotecan.

Abstract

8505 Background: Multi-lineage myelosuppression is an acute toxicity of cytotoxic chemotherapy leading to hematologic adverse events and dose reductions and delays. Current therapies are lineage specific and administered after chemotherapy damage.Trilaciclib (T), a highly selective, reversible CDK4/6 inhibitor, is designed to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy (myelopreservation). We have shown that T mitigates myelosuppression in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) receiving 1 st -line chemotherapy. Methods: In this blinded, placebo-controlled, multicenter Phase 2 study, patients with previously treated ES-SCLC were randomized to T (240 mg/m 2 ) + 0.75 mg/m 2 topotecan, T (240 mg/m 2 ) + 1.5 mg/m 2 topotecan, or placebo (P) + 1.5 mg/m 2 topotecan IV on days 1-5 of 21-day cycles. Patients had access to standard supportive care, except in cycle 1 where prophylactic growth factors were not allowed. Eligible patients had adequate organ function, measurable disease, ECOG PS 0-2, and disease progression during or after prior 1 st /2 nd -line chemotherapy. Objectives included safety, tolerability, measures of myelosuppression and tumor efficacy. Results: 91 patients were randomized: 30 patients received T + 0.75 mg/m 2 topotecan, 32 patients received T + 1.5 mg/m 2 topotecan and 28 patients received P + 1.5 mg/m 2 topotecan. In patients receiving 1.5 mg/m 2 topotecan, T treatment reduced occurrence [40.6% (T) vs 75.6% (P), p = 0.016], and duration in cycle 1 [2 days (T) vs 8 days (P), p = < 0.0001] of severe neutropenia. T-treated patients had fewer RBC transfusions on/after 5 weeks on study, GCSF administrations, and all-cause dose reductions. Chemotherapy efficacy was comparable in both arms (P and T) treated with 1.5 mg/m 2 topotecan (median PFS (T) 4.2 months vs (P) 4.2 months, HR = 0.83). OS data is immature. Conclusions: T combined with topotecan mitigated chemotherapy-induced myelosuppression and improved tolerability of topotecan vs P. Results suggest the addition of T to cytotoxic chemotherapy for the treatment of ES-SCLC is clinically beneficial. Clinical trial information: NCT02514447.