TY - JOUR
T1 - Lurbinectedin as second-line treatment for patients with small-cell lung cancer
T2 - a single-arm, open-label, phase 2 basket trial
AU - Trigo, José
AU - Subbiah, Vivek
AU - Besse, Benjamin
AU - Moreno, Victor
AU - López, Rafael
AU - Sala, María Angeles
AU - Peters, Solange
AU - Ponce, Santiago
AU - Fernández, Cristian
AU - Alfaro, Vicente
AU - Gómez, Javier
AU - Kahatt, Carmen
AU - Zeaiter, Ali
AU - Zaman, Khalil
AU - Boni, Valentina
AU - Arrondeau, Jennifer
AU - Martínez, Maite
AU - Delord, Jean Pierre
AU - Awada, Ahmad
AU - Kristeleit, Rebecca
AU - Olmedo, Maria Eugenia
AU - Wannesson, Luciano
AU - Valdivia, Javier
AU - Rubio, María Jesús
AU - Anton, Antonio
AU - Sarantopoulos, John
AU - Chawla, Sant P.
AU - Mosquera-Martinez, Joaquín
AU - D'Arcangelo, Manolo
AU - Santoro, Armando
AU - Villalobos, Victor M.
AU - Sands, Jacob
AU - Paz-Ares, Luis
N1 - Funding Information:
JT reports personal fees for scientific advice and speaker roles from AstraZeneca, Bristol-Myers Squibb, Merck Serono, Pfizer, and Roche; advisory board fees from Boehringer Ingelheim and Takeda; and travel grants from Bristol-Myers Squibb and MSD, outside the submitted work. VS reports clinical trials research support from Altum, Amgen, AbbVie, Agensys, Bayer, Berghealth, Blueprint Medicines, Boston Medical, Celgene, D3, Dragonfly therapeutics, Exelexis, Fujifilm, GlaxoSmithKline, Idera Pharma, Incyte, Inhibrx, LOXO Oncology, MedImmune, Multivir, Nanocarrier, Northwest Biotherapeutics, Novartis, Pfizer, Roche-Genentech, Takeda, and Vegenics, outside the submitted work; and declared National Comprehensive Cancer Network, National Cancer Institute Cancer Therapy Evaluation Program, University of Texas MD Anderson Cancer Center, and travel support from Novartis, Pharma Mar, American Society of Clinical Oncology, European Society for Medical Oncology, Helsin, and Incyte; and advisory board fees from Helsinn, LOXO Oncology, R-Pharma US, Incyte, and MedImmune. BB reports grants from Biogen, Blueprint Medicines, Celgene, GlaxoSmithKline, Ingnyta, Ipsen, Merck, MSD Oncology, Nektar, Spectrum Pharmaceuticals, Takeda, and Tiziana Therapeutics, outside the submitted work. VM reports personal fees for advisory roles from Bristol-Myers Squibb and Hanssen, outside the submitted work. RL reports grants and fees for advisory board membership, accommodation, lectures, research grants, and travel from Bayer, Bristol-Myers Squibb, Eli Lilly, Merck, Pharma Mar, Pierre Fabre, Novartis, Pfizer, and Roche, outside the submitted work. SPe reports advisory board fees from AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bioinvent, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daichi Sankyo, Debiopharm, Eli Lilly, Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, and Takeda; speaker fees for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Roche, MSD, Novartis, Pfizer, Takeda; and clinical trial fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Roche, Illumina, MSD, Merck Serono, Novartis, Pfizer, and Sanofi, outside the submitted work. CF, VA, JG, CK, and AZ report grants from the Centro para el Desarrollo Tecnológico Industrial during the conduct of the study; and are full-time employees of and own stock from Pharma Mar. AAw reports travel grants, advisory board, and speaker fees from Bristol-Myers Squibb, Novartis, Eisai, Ipsen, Leo Pharma Lilly, Pfizer, and Roche, outside the submitted work. JV reports speaker fees from Bristol-Myers Squibb and transport and congress attendance fees from Novartis, outside the submitted work. JSar declares a grant from the Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio, outside the submitted work. SPC reports non-financial support from Pharma Mar (drug supply), outside the submitted work. AS reports advisory board fees from Bayer, Bristol-Myers Squibb, Eisai, Gilead, MSD, Pfizer, and Servier; speakers' bureau fees from AbbVie, Amgen, Arqule, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Eisai, Gilead, Lilly, MSD, Novartis, Roche, Sandoz, Servier, Pfizer, and Takeda; and is a consultant for Arqule and Sanofi, outside the submitted work. VMV reports advisory board fees from AbbVie, Agios, Blueprint, Janssen, Lilly, Nanocarrier, and Springworks, outside the submitted work. JSan reports consulting and advisory board fees from AbbVie, AstraZeneca, Celgene, Foundation Medicine, Genentech, Guardant, Incyte, Loxo, Merck, Trovagene, and Medtronic, outside the submitted work. LP-A reports grants from Bristol-Myers Squibb and Pfizer, and consultant and speaker fees from Adacap, Amgen, Bayer, Blueprint, Boehringer Ingelheim, Celgene, Incyte, Ipsen, Sanofi, Servier, Sysmex, and from Altum Sequencing as co-founder and board member outside the submitted work. All other authors declare no competing interests.
Funding Information:
The study was funded by Pharma Mar. We thank the patients, their families, and the investigator teams; Daniel Castellano, Jerome Alexandre, Alexandra Leary, Bernard Doger, Federico Longo, Geoffrey Shappiro, and Luis Miguel Ant?n Aparicio for their collaboration; and Ana Garc?a, Ana Maria Jim?nez, Antonio Nieto, Carmen Parra, Cristina Garrido, Elena Est?vez, Elena Delgado, Herv? Dhellot, Isabel Valero, Isabel Pardos, Itziar L?pez-Oleaga, Mariano Siguero, Jorge Iglesias, Jose Antonio L?pez-Vilari?o, Liliana Navarro, Maria Paz, Nadia Torres, Pilar Lardelli, and Rosario Moreno from the Pharma Mar team during the study conduct. Cancer Center Support Grant P30CA054174 was received by the Institute for Drug Development, Mays Cancer Center, University of Texas, and M D Anderson Cancer Center (San Antonio, TX, USA).
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
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U2 - 10.1016/S1470-2045(20)30068-1
DO - 10.1016/S1470-2045(20)30068-1
M3 - Article
C2 - 32224306
AN - SCOPUS:85083862832
SN - 1470-2045
VL - 21
SP - 645
EP - 654
JO - The lancet oncology
JF - The lancet oncology
IS - 5
ER -