Trabectedin in Malignant Pleural Mesothelioma: Results From the Multicentre, Single Arm, Phase II ATREUS Study

• Published in: Clinical lung cancer 2021-07, Vol.22 (4), p.361-370.e3
• Main Authors: Cortinovis, Diego, Grosso, Federica, Carlucci, Luciano, Zucali, Paolo Andrea, Pasello, Giulia, Tiseo, Marcello, Sperandi, Francesca, Hollander, Lital, Galli, Francesca, Torri, Valter, Rulli, Eliana, Canova, Stefania, Maconi, Antonio, Bidoli, Paolo, Ceresoli, Giovanni Luca, D’Incalci, Maurizio
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - adverse effects; Chemical and Drug Induced Liver Injury - epidemiology; Chemical and Drug Induced Liver Injury - etiology; Female; Hepatotoxicity; Humans; Male; Mesothelioma; Mesothelioma, Malignant - drug therapy; Mesothelioma, Malignant - pathology; Middle Aged; Nonepithelioid; Pleural Neoplasms - drug therapy; Pleural Neoplasms - pathology; Progression-Free Survival; Second-line treatment; Survival Rate; Trabectedin; Trabectedin - administration & dosage; Trabectedin - adverse effects; Treatment Outcome; Tumor Microenvironment
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2020.06.028

New therapeutic approaches in unresectable malignant pleural mesothelioma (MPM) are eagerly awaited. Trabectedin is an antitumor agent with an effect on cancer cell proliferation and a modulating action on tumor microenvironment. The ATREUS study explored the activity and safety of trabectedin in patients with unresectable MPM. Epithelioid patients with MPM received trabectedin as second-line while biphasic/sarcomatoid patients with MPM as first- or second-line therapy. Treatment was given intravenously at an initially planned dose of 1.3 mg/m2 every 3 weeks, until progression or unacceptable toxicity. The primary endpoint was progression-free survival rate at 12 weeks (PFS12wks). Overall, 78 patients (54%) had epithelioid and 67 (46%) nonepithelioid MPM. PFS12wks in 62 evaluable patients with epithelioid MPM was 43.5% (80% confidence interval 34.9%-52.5%); median progression-free and overall survival were 2.4 and 9.0 months, respectively. PFS12wks in 52 evaluable patients with nonepithelioid MPM was 30.8% (90% confidence interval 20.3%-42.9%); median progression-free and overall survival were 1.7 and 5.4 months. Trabectedin starting dose was amended due to excess of liver toxicity. Eighty-four (64%) and 48 (36%) patients received 1.3 mg/m2 and 1.1. mg/m2, respectively. The most common grade 3-4 toxicities were hepatotoxicity, leukopenia/neutropenia, and fatigue. Grade 3-4 hepatotoxicity was reported in 59 (70%) patients treated at 1.3 mg/m2, and in 19 (40%) treated at 1.1 mg/m2. Trabectedin showed modest clinical activity, at the expense of relevant liver toxicity. Further development of this drug in MPM at full doses is not warranted. ATREUS was a phase II, single arm, multicenter study aimed at exploring the activity and safety of trabectedin in 78 epithelioid patients and 67 nonepithelioid patients with unresectable malignant pleural mesothelioma. Trabectedin showed modest clinical activity, at the expense of relevant liver toxicity.