Randomized phase II study on gemcitabine with or without ramucirumab as second-line treatment for advanced malignant pleural mesothelioma (MPM): Results of Italian Rames Study.

American Society of Clinical Oncology (ASCO) - Tập 38 Số 15_suppl - Trang 9004-9004 - 2020
Maria Pagano1, Giovanni Luca Ceresoli2, Paolo Andrea Zucali3, Giulia Pasello4, Marina Chiara Garassino5, Federica Grosso6, Marcello Tiseo7, Héctor Soto Parrà8, Francesca Zanelli9, Federico Cappuzzo10, Francesco Grossi11, Filippo de Marinis12, Paolo Pedrazzoli13, R. Gnoni1, Candida Bonelli14, Annalisa Berselli1, Luca Boni15, Nicola Normanno16, Carmine Pinto1
1Oncology Unit, Clinical Cancer Center, AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italy;
2Medical Oncology, Cliniche Humanitas Gavazzeni, Bergamo, Italy;
3Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Italy
4Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy
5Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
6SS Antonio e Biagio Hospital, Department of Oncology, Alessandria, Italy;
7Medical Oncology Unit, University Hospital of Parma, Parma, ITALY
8Medical Oncology, University Hospital Policlinico, Vittorio Emanuele, Catania, Italy;
9Oncology Unit, Clinical Cancer Center, AUSL-IRCCS Reggio Emilia, Modena, Italy;
10Istituto Toscano Tumori-Ospedale Civile Livorno, Livorno, Italy;
11Lung Cancer Unit, Ospedale Policlinico San Martino, Genoa, Italy
12Istituto Europeo di Oncologia, IRCCS, Milan, Italy
13Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
14Oncology Unit, Clinical Cancer Centre, IRCCS-AUSL di Reggio Emilia, Reggio Emilia, Italy;
15Unità Operativa Epidemiologia Clinica IRCCS Ospedale Policlinico San Martino, Genoa, Italy;
16Cell Biology and Biotherapy, INT-Fondazione Pascale, Naples, Italy;

Tóm tắt

9004 Background. The RAMES Study (EudraCT Number 2016-001132-36) is a multicenter, double-blind, randomized phase II trial exploring the efficacy and the safety of the addition of ramucirumab to gemcitabine as the second-line treatment in MPM patients (pts) after platinum/pemetrexed regimens. Methods. The pts were assigned (1:1) to receive Gemcitabine 1000 mg/m2 i v on days 1 and 8 every 21 days with Placebo (Arm A) or Ramucirumab 10 mg/kg i v on day 1, of a 21-day cycle (Arm B), until tolerability or progressive disease. Pts was stratified by ECOG/PS (0-1 vs 2), age (≤ 70 vs > 70 yrs), histology (epithelioid vs non-epithelioid) and time to progression (TTP) after first-line therapy. The primary endpoint was overall survival (OS). Assuming a proportion of OS equal to 40% at 1 year in arm A, a 12% absolute improvement in OS at 1 yrs was expected in Arm B (hazard ratio = 0.70).114 events (156 subjects) are required for a one-sided log-rank test with α = 0.15 to have 80% power. Results. From December 2016 to July 2018, 164 pts were randomized, 81 pts in Arm A and 80 Arm B; 3 pts were randomized but not treated. Characteristics of pts were: median age 69 yrs (44-81), males 119 (73.9%), females 42 (26.1%); ECOG/PS0 96 (59.6%) ECOG/PS1-2 65 (40.4%); histotype epithelioid 132 (81.9%), non-epithelioid 29 (18.1%); stage III 98 (60.7%), stage IV 60 (37.3%), 3 (2.0%) missing; asbestos exposure assessed 80 (49.7%). Median of courses was 3.50 in Arm A and 7.50 in Arm B. OS was significantly longer in Arm B with median 13.8 mths (70% CI 12.7-14.4) vs Arm A with 7.5 mths (70% CI 6.9-8.9), HR 0.71 (70% CI 0.59-0.85, p = 0.057). OS at 6 and 12 mths was in Arm A 63.9% and 33.9%, and in Arm B 74.7% and 56.5%, respectively. In Arm B OS was not correlated to TTP at first-line therapy (13.6 mths in TTP ≤6 mths and 13.9 mths in TTP > 6 mths) and histotypes (13.8 months in the epithelioid and 13.0 months in non-epithelioid). No significant differences in thromboembolism G3-4 events were observed in Arm A vs Arm B (p= 0.64). None hypertension G3-4 was reported in Arm A vs 5 pts (6.3%) in Arm B (p= 0.022). No significant differences in G3-4 haematological toxicities between the two arms were reported. Conclusion: In the RAMES Study the addition of Ramucirumab to Gemcitabine significantly improved OS regardless of age of pts, tumor histotype and TTP at the first-line treatment. Gemcitabine plus Ramucirumab can be considered a manageable regimen in second-line treatment of advanced MPM pts. Clinical trial information: NTC03560973.

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American Society of Clinical Oncology (ASCO)

Tập 38 Số 15_suppl

9004-9004

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