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

Clinical Lung Cancer 2020 July 3 [Link]

Diego Cortinovis, Federica Grosso, Luciano Carlucci, Paolo Andrea Zucali, Giulia Pasello, Marcello Tiseo, Francesca Sperandi, Lital Hollander, Francesca Galli, Valter Torri, Eliana Rulli, Stefania Canova, Antonio Maconi, Paolo Bidoli, Giovanni Luca Ceresoli , Maurizio D’Incalci, ATREUS investigators


Introduction: 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.

Methods: 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).

Results: 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.

Conclusions: 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.