Author(s): Diego Luigi Cortinovis, Lital Hannah Hollander, Irene Claudia Floriani, Federica Grosso, Alessandro Marinello, Giovanni Luca Ceresoli, Ilaria Pacchetti, Paolo Andrea Zucali, Maurizio D'Incalci, Stefania Canova, Maria Ida Abbate, Francesca Ugo, Suela Vukcaj, Paolo Bidoli; Az Ospedale S. Gerardo, Monza, Italy; IRCCS - Mario Negri Institute for Pharmacological Research, Milano, Italy; Oncology SS Antonio e Biagio General Hospital, Alessandria, Italy; Department of Oncology, Istituto Humanitas Gavazzeni, Bergamo, Italy; Humanitas Cancer Center, Rozzano, Italy; IRCCS Mario Negri Institute for Pharmacological Research Oncology Department, Milan, Italy; A.O. San Gerardo, Monza, Italy; SC Oncologia SS Antonio e Biagio and C Arrigo Hospital, Alessandria, Italy; Ospedale S Gerardo, Monza, ItalyAbstract Disclosures
Abstract:
Background: The efficacy of available MPM therapies is poor in patients (pts) with sarcomatoid/biphasic histotypes , and their prognosis remains dismal. The use of Trabectedin (T) in MPM is justified by its peculiar mechanism of action, involving modulation of the tumor’s inflammatory microenvironment, and the demonstrated activity against a range of tumours, including sarcomas. We aimed to study the activity and safety of T in pts with both epithelioid and biphasic/sarcomatoid MPM. Methods: ATREUS, an Italian multicenter single arm phase II trial, evaluates T as second line therapy in pts with epithelioid histotype and as first/second line in biphasic/sarcomatoid pts. In the latter cohort, the study needed to enroll 17 evaluable pts to reject with a 10% one sided alpha error the null hypothesis that 12-week progression free survival (12w PFS) is ≤ 15% and an 85% power to show 12w PFS in ≥ 40% of pts. Overall survival and safety were secondary endpoints. Pts were treated with T, 1.3 mg/m2, over 3 hours every 21 days, until progression or unacceptable toxicity.
Results: The cohort of sarcomatoid/biphasic pts is now complete and results are reported below. Twenty three pts were enrolled and 17 were evaluable (14 M and 3 F, median age 67.9 years). Ten, six and one pts had stage IV, III and II disease, respectively. Seven (41.2%) were treatment naïve. At 12 weeks 7/17 pts (41.2%, 95% CI: 18.4-67.1) were alive and free of progression. Five patients (29.4%) had sustained response with PFS ≥ 18 weeks. By the time of analysis all pts interrupted treatment. Interruption reasons were disease progression in 12 pts, death (4 pts) and consent withdrawal in one pt. The most frequent grade ≥ 3 treatment related toxicities were non febrile neutropenia (11.8%), nausea (17.6%), vomiting, mucositis and fever/infection (each observed in one patient, 5.9%). Two serious adverse events , classified as possibly related to T, occurred. One was fatal.
Conclusions: T demonstrated its activity in terms of PFS and was well tolerated in this population of patients with advanced sarcomatoid/biphasic MPM. These optimistic results merit to be further investigated in a larger sample.