1. Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).
- Author
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Proto C, Ganzinelli M, Manglaviti S, Imbimbo M, Galli G, Marabese M, Zollo F, Alvisi MF, Perrino M, Cordua N, Borea F, de Vincenzo F, Chella A, Cappelli S, Pardini E, Ballatore Z, Lucarelli A, Ambrosini E, Giuliano M, Pietroluongo E, Mulargiu C, Fabbri A, Prelaj A, Occhipinti M, Brambilla M, Mazzeo L, Beninato T, Vigorito R, Ruggirello M, Greco FG, Calareso G, Miliziano D, Rulli E, De Simone I, Torri V, de Braud FGM, Pasello G, De Placido P, Berardi R, Petrini I, Zucali P, Garassino MC, and Lo Russo G
- Subjects
- Humans, Male, Middle Aged, Female, Aged, Adult, Progression-Free Survival, Survival Rate, Ramucirumab, Carboplatin administration & dosage, Carboplatin adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Paclitaxel administration & dosage, Paclitaxel adverse effects, Thymus Neoplasms drug therapy, Thymus Neoplasms pathology, Thymus Neoplasms mortality, Thymoma drug therapy, Thymoma pathology, Thymoma mortality
- Abstract
Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC., Patients and Methods: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out., Results: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3., Conclusions: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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