1900P - RAMES trial: A multicentre, double-blind, randomized, phase II study on gemcitabine plus ramucirumab versus gemcitabine alone as second-line treatment for advanced malignant pleural mesothelioma (MPM)

Background

The Ramucirumab Mesothelioma clinical trial (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 2°line treatment in patients with MPM.

Methods

The pts were assigned (1:1) to receive Gemcitabine 1000 mg/m² iv on days 1 and 8 every 21 days with Placebo or Ramucirumab 10 mg/kg iv on day 1, of a 21-day cycle, until tolerability or PD. Pts randomised 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 1°line therapy. The primary endpoint was overall survival (OS). Assuming a proportion of OS equal to 40% at 1 years in arm A, a 12% absolute improvement in OS at 1 years was expected in Arm B (hazard ratio = 0.70). 114 events (156 subjects) are required for a one-sided log-rank test with alfa = 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%); 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 1°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 between Arm A and 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).

Conclusions

In the RAMES Study the addition of Ramucirumab to Gemcitabine significantly improved OS and can be considered a manageable regimen in 2°line treatment in MPM pts.

Clinical trial identification

EudraCT number 2016-001132-36.

Editorial acknowledgement

Legal entity responsible for the study

Goirc group.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.