Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study

Invest New Drugs. 2021 Oct;39(5):1275-1283. doi: 10.1007/s10637-020-01025-x. Epub 2021 Mar 11.

Abstract

Background A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC). An expansion cohort further evaluated this combination. Patients and methods Twenty-eight patients with relapsed SCLC after no more than one line of cytotoxic-containing chemotherapy were treated: 18 (64%) with sensitive disease (chemotherapy-free interval [CTFI] ≥90 days) and ten (36%) with resistant disease (CTFI <90 days; including six with refractory disease [CTFI ≤30 days]). Results Ten patients showed confirmed response (overall response rate [ORR] = 36%); median progression-free survival (PFS) = 3.3 months; median overall survival (OS) = 7.9 months. ORR was 50% in sensitive disease (median PFS = 5.7 months; median OS = 11.5 months) and 10% in resistant disease (median PFS = 1.3 months; median OS = 4.6 months). The main toxicity was transient and reversible myelosuppression. Treatment-related non-hematological events (fatigue, nausea, decreased appetite, vomiting, alopecia) were mostly mild or moderate. Conclusion Doxorubicin 40 mg/m2 and lurbinectedin 2.0 mg/m2 on Day 1 q3wk has shown noteworthy activity in relapsed SCLC and a manageable safety profile. The combination is being evaluated as second-line therapy for SCLC in an ongoing, randomized phase III trial. Clinical trial registration www.ClinicalTrials.gov code: NCT01970540. Date of registration: 22 October, 2013.

Keywords: Lurbinectedin; PM01183; Phase I study; Small cell lung cancer.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carbolines / administration & dosage
  • Carbolines / adverse effects
  • Carbolines / therapeutic use*
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Heterocyclic Compounds, 4 or More Rings / administration & dosage
  • Heterocyclic Compounds, 4 or More Rings / adverse effects
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use*
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Progression-Free Survival
  • Small Cell Lung Carcinoma / drug therapy*

Substances

  • Antineoplastic Agents
  • Carbolines
  • Heterocyclic Compounds, 4 or More Rings
  • PM 01183
  • Doxorubicin

Associated data

  • ClinicalTrials.gov/NCT01970540