Journal article
Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial.
- Trigo J Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Málaga, Spain. Electronic address: jmtrigo@seom.org.
- Subbiah V MD Anderson Cancer Center, Houston, TX, USA.
- Besse B Gustave Roussy Cancer Campus, Villejuif, France; Paris Sud University, Orsay, France.
- Moreno V START Madrid-Fundación Jiménez Díaz, Hospital Fundación Jiménez Díaz, Madrid, Spain.
- López R Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
- Sala MA Organización Sanitaria Integrada Bilbao Basurto, Bilbao, Spain.
- Peters S University Hospital Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Ponce S Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
- Fernández C Pharma Mar, Clinical Research and Development, Colmenar Viejo, Madrid, Spain.
- Alfaro V Pharma Mar, Clinical Research and Development, Colmenar Viejo, Madrid, Spain.
- Gómez J Pharma Mar, Clinical Research and Development, Colmenar Viejo, Madrid, Spain.
- Kahatt C Pharma Mar, Clinical Research and Development, Colmenar Viejo, Madrid, Spain.
- Zeaiter A Pharma Mar, Clinical Research and Development, Colmenar Viejo, Madrid, Spain.
- Zaman K University Hospital Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Boni V START Madrid-Centro Integral Oncológico Clara Campal, Hospital Universitario Sanchinarro, Madrid, Spain.
- Arrondeau J Hôpital Cochin, Paris, France.
- Martínez M Complejo Hospitalario de Navarra, Pamplona, Spain.
- Delord JP Institut Claudius Regaud, Toulouse, France.
- Awada A Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
- Kristeleit R University College London Cancer Institute, London, UK.
- Olmedo ME Hospital Universitario Ramón y Cajal, Madrid, Spain.
- Wannesson L Ospedale San Giovanni, Bellinzona, Switzerland.
- Valdivia J Hospital Universitario Virgen de las Nieves, Granada, Spain.
- Rubio MJ Hospital Universitario Reina Sofía, Cordoba, Spain.
- Anton A Hospital Universitario Miguel Servet, Zaragoza, Spain.
- Sarantopoulos J Institute for Drug Development, Mays Cancer Center at University of Texas Health San Antonio, MD Anderson Cancer Center, San Antonio, TX, USA.
- Chawla SP Sarcoma Oncology Center, Santa Monica, CA, USA.
- Mosquera-Martinez J Complexo Hospitalario Universitario A Coruña, A Coruña, Spain.
- D'Arcangelo M Ospedale Santa Maria delle Croci, Ravenna, Italy.
- Santoro A Istituto Clinico Humanitas, Rossano, Italy.
- Villalobos VM University of Colorado Cancer Center, Aurora, CO, USA.
- Sands J Dana-Farber Cancer Institute, Boston, MA, USA.
- Paz-Ares L Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
- 2020-04-01
Published in:
- The Lancet. Oncology. - 2020
Administration, Intravenous
Aged
Antineoplastic Combined Chemotherapy Protocols
Carbolines
Disease-Free Survival
Doxorubicin
Female
Heterocyclic Compounds, 4 or More Rings
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Small Cell Lung Carcinoma
Treatment Outcome
English
BACKGROUND
Few options exist for treatment of patients with small-cell lung cancer (SCLC) after failure of first-line therapy. Lurbinectedin is a selective inhibitor of oncogenic transcription. In this phase 2 study, we evaluated the acti and safety of lurbinectedin in patients with SCLC after failure of platinum-based chemotherapy.
METHODS
In this single-arm, open-label, phase 2 basket trial, we recruited patients from 26 hospitals in six European countries and the USA. Adults (aged ≥18 years) with a pathologically proven diagnosis of SCLC, Eastern Cooperative Oncology Group performance status of 2 or lower, measurable disease as per Response Criteria in Solid Tumors (RECIST) version 1.1, absence of brain metastasis, adequate organ function, and pre-treated with only one previous chemotherapy-containing line of treatment (minimum 3 weeks before study initiation) were eligible. Treatment consisted of 3·2 mg/m2 lurbinectedin administered as a 1-h intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. The primary outcome was the proportion of patients with an overall response (complete or partial response) as assessed by the investigators according to RECIST 1.1. All treated patients were analysed for activity and safety. This study is ongoing and is registered with ClinicalTrials.gov, NCT02454972.
FINDINGS
Between Oct 16, 2015, and Jan 15, 2019, 105 patients were enrolled and treated with lurbinectedin. Median follow-up was 17·1 months (IQR 6·5-25·3). Overall response by investigator assessment was seen in 37 patients (35·2%; 95% CI 26·2-45·2). The most common grade 3-4 adverse events (irrespective of causality) were haematological abnormalities-namely, anaemia (in nine [9%] patients), leucopenia (30 [29%]), neutropenia (48 [46%]), and thrombocytopenia (seven [7%]). Serious treatment-related adverse events occurred in 11 (10%) patients, of which neutropenia and febrile neutropenia were the most common (five [5%] patients for each). No treatment-related deaths were reported.
INTERPRETATION
Lurbinectedin was active as second-line therapy for SCLC in terms of overall response and had an acceptable and manageable safety profile. Lurbinectedin could represent a potential new treatment for patients with SCLC, who have few options especially in the event of a relapse, and is being investigated in combination with doxorubicin as second-line therapy in a randomised phase 3 trial.
FUNDING
Pharma Mar.
Few options exist for treatment of patients with small-cell lung cancer (SCLC) after failure of first-line therapy. Lurbinectedin is a selective inhibitor of oncogenic transcription. In this phase 2 study, we evaluated the acti and safety of lurbinectedin in patients with SCLC after failure of platinum-based chemotherapy.
METHODS
In this single-arm, open-label, phase 2 basket trial, we recruited patients from 26 hospitals in six European countries and the USA. Adults (aged ≥18 years) with a pathologically proven diagnosis of SCLC, Eastern Cooperative Oncology Group performance status of 2 or lower, measurable disease as per Response Criteria in Solid Tumors (RECIST) version 1.1, absence of brain metastasis, adequate organ function, and pre-treated with only one previous chemotherapy-containing line of treatment (minimum 3 weeks before study initiation) were eligible. Treatment consisted of 3·2 mg/m2 lurbinectedin administered as a 1-h intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. The primary outcome was the proportion of patients with an overall response (complete or partial response) as assessed by the investigators according to RECIST 1.1. All treated patients were analysed for activity and safety. This study is ongoing and is registered with ClinicalTrials.gov, NCT02454972.
FINDINGS
Between Oct 16, 2015, and Jan 15, 2019, 105 patients were enrolled and treated with lurbinectedin. Median follow-up was 17·1 months (IQR 6·5-25·3). Overall response by investigator assessment was seen in 37 patients (35·2%; 95% CI 26·2-45·2). The most common grade 3-4 adverse events (irrespective of causality) were haematological abnormalities-namely, anaemia (in nine [9%] patients), leucopenia (30 [29%]), neutropenia (48 [46%]), and thrombocytopenia (seven [7%]). Serious treatment-related adverse events occurred in 11 (10%) patients, of which neutropenia and febrile neutropenia were the most common (five [5%] patients for each). No treatment-related deaths were reported.
INTERPRETATION
Lurbinectedin was active as second-line therapy for SCLC in terms of overall response and had an acceptable and manageable safety profile. Lurbinectedin could represent a potential new treatment for patients with SCLC, who have few options especially in the event of a relapse, and is being investigated in combination with doxorubicin as second-line therapy in a randomised phase 3 trial.
FUNDING
Pharma Mar.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/S1470-2045(20)30068-1
- PMID 32224306
- Persistent URL
- https://sonar.ch/global/documents/268637
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