José Trigo1, Vivek Subbiah2, Benjamin Besse3, Victor Moreno4, Rafael López5, María Angeles Sala6, Solange Peters7, Santiago Ponce8, Cristian Fernández9, Vicente Alfaro9, Javier Gómez9, Carmen Kahatt9, Ali Zeaiter9, Khalil Zaman7, Valentina Boni10, Jennifer Arrondeau11, Maite Martínez12, Jean-Pierre Delord13, Ahmad Awada14, Rebecca Kristeleit15, Maria Eugenia Olmedo16, Luciano Wannesson17, Javier Valdivia18, María Jesús Rubio19, Antonio Anton20, John Sarantopoulos21, Sant P Chawla22, Joaquín Mosquera-Martinez23, Manolo D'Arcangelo24, Armando Santoro25, Victor M Villalobos26, Jacob Sands27, Luis Paz-Ares8. 1. Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Málaga, Spain. Electronic address: jmtrigo@seom.org. 2. MD Anderson Cancer Center, Houston, TX, USA. 3. Gustave Roussy Cancer Campus, Villejuif, France; Paris Sud University, Orsay, France. 4. START Madrid-Fundación Jiménez Díaz, Hospital Fundación Jiménez Díaz, Madrid, Spain. 5. Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. 6. Organización Sanitaria Integrada Bilbao Basurto, Bilbao, Spain. 7. University Hospital Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 8. 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. 9. Pharma Mar, Clinical Research and Development, Colmenar Viejo, Madrid, Spain. 10. START Madrid-Centro Integral Oncológico Clara Campal, Hospital Universitario Sanchinarro, Madrid, Spain. 11. Hôpital Cochin, Paris, France. 12. Complejo Hospitalario de Navarra, Pamplona, Spain. 13. Institut Claudius Regaud, Toulouse, France. 14. Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 15. University College London Cancer Institute, London, UK. 16. Hospital Universitario Ramón y Cajal, Madrid, Spain. 17. Ospedale San Giovanni, Bellinzona, Switzerland. 18. Hospital Universitario Virgen de las Nieves, Granada, Spain. 19. Hospital Universitario Reina Sofía, Cordoba, Spain. 20. Hospital Universitario Miguel Servet, Zaragoza, Spain. 21. Institute for Drug Development, Mays Cancer Center at University of Texas Health San Antonio, MD Anderson Cancer Center, San Antonio, TX, USA. 22. Sarcoma Oncology Center, Santa Monica, CA, USA. 23. Complexo Hospitalario Universitario A Coruña, A Coruña, Spain. 24. Ospedale Santa Maria delle Croci, Ravenna, Italy. 25. Istituto Clinico Humanitas, Rossano, Italy. 26. University of Colorado Cancer Center, Aurora, CO, USA. 27. Dana-Farber Cancer Institute, Boston, MA, USA.
Abstract
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 withlurbinectedin. 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.
RCT Entities:
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.
Authors: Anish Thomas; Nobuyuki Takahashi; Vinodh N Rajapakse; Xiaohu Zhang; Yilun Sun; Michele Ceribelli; Kelli M Wilson; Yang Zhang; Erin Beck; Linda Sciuto; Samantha Nichols; Brian Elenbaas; Janusz Puc; Heike Dahmen; Astrid Zimmermann; Jillian Varonin; Christopher W Schultz; Sehyun Kim; Hirity Shimellis; Parth Desai; Carleen Klumpp-Thomas; Lu Chen; Jameson Travers; Crystal McKnight; Sam Michael; Zina Itkin; Sunmin Lee; Akira Yuno; Min-Jung Lee; Christophe E Redon; Jessica D Kindrick; Cody J Peer; Jun S Wei; Mirit I Aladjem; William Douglas Figg; Seth M Steinberg; Jane B Trepel; Frank T Zenke; Yves Pommier; Javed Khan; Craig J Thomas Journal: Cancer Cell Date: 2021-04-12 Impact factor: 31.743
Authors: Zhicheng Niu; Shenghu Guo; Jing Cao; Yuehua Zhang; Xiaojin Guo; Francesco Grossi; Yoshinobu Ichiki; You Li; Zhiyu Wang Journal: Ann Transl Med Date: 2021-04
Authors: A-M C Dingemans; M Früh; A Ardizzoni; B Besse; C Faivre-Finn; L E Hendriks; S Lantuejoul; S Peters; N Reguart; C M Rudin; D De Ruysscher; P E Van Schil; J Vansteenkiste; M Reck Journal: Ann Oncol Date: 2021-04-20 Impact factor: 51.769