Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial - 28/09/21
, Maria Pagano, MD a, Federica Grosso, MD d, e, Giulia Pasello, MD f, g, Marina Chiara Garassino, MD h, Marcello Tiseo, MD i, j, Hector Soto Parra, MD k, Francesco Grossi, MD l, m, Federico Cappuzzo, MD n, Filippo de Marinis, MD o, Paolo Pedrazzoli, MD p, q, Maria Bonomi, MD r, s, Letizia Gianoncelli, MD r, t, Matteo Perrino, MD c, Armando Santoro, MD b, c, Francesca Zanelli, MD a, Candida Bonelli, MD a, Antonio Maconi, MD e, Stefano Frega, MD g, Erika Gervasi, MD a, Luca Boni, MD u, Giovanni Luca Ceresoli, MD rSummary |
Background |
There is a preclinical rationale for inhibiting angiogenesis in mesothelioma. We aimed to assess the efficacy and safety of the anti-VEGFR-2 antibody ramucirumab combined with gemcitabine in patients with pretreated malignant pleural mesothelioma.
Methods |
RAMES was a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial done at 26 hospitals in Italy. Eligible patients were aged 18 years or older, had Eastern Cooperative Oncology Group performance status 0–2, and histologically proven malignant pleural mesothelioma progressing during or after first-line treatment with pemetrexed plus platinum. Patients were randomly assigned (1:1) to receive intravenous gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks plus either intravenous placebo (gemcitabine plus placebo group) or ramucirumab 10 mg/kg (gemcitabine plus ramucirumab group) on day 1 every 3 weeks, until tumour progression or unacceptable toxicity. Central randomisation was done according to a minimisation algorithm method, associated with a random element using the following stratification factors: ECOG performance status, age, histology, and first-line time-to-progression. The primary endpoint was overall survival, measured from the date of randomisation to the date of death from any cause. Efficacy analyses were assessed in all patients who had been correctly randomised and received their allocated treatment, and safety analyses were assessed in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03560973, and with EudraCT, 2016-001132-36.
Findings |
Between Dec 22, 2016, and July 30, 2018, of 165 patients enrolled 161 were correctly assigned and received either gemcitabine plus placebo (n=81) or gemcitabine plus ramucirumab (n=80). At database lock (March 8, 2020), with a median follow-up of 21·9 months (IQR 17·7–28·5), overall survival was longer in the ramucirumab group (HR 0·71, 70% CI 0·59–0·85; p=0·028). Median overall survival was 13·8 months (70% CI 12·7–14·4) in the gemcitabine plus ramucirumab group and 7·5 months (6·9–8·9) in the gemcitabine plus placebo group. Grade 3–4 treatment-related adverse events were reported in 35 (44%) of 80 patients in the gemcitabine plus ramucirumab group and 24 (30%) of 81 in the gemcitabine plus placebo group. The most common treatment-related grade 3–4 adverse events were neutropenia (16 [20%] for gemcitabine plus ramucirumab vs ten [12%] for gemcitabine plus placebo) and hypertension (five [6%] vs none). Treatment-related serious adverse events were reported in five (6%) in the gemcitabine plus ramucirumab group and in four (5%) patients in the gemcitabine plus placebo group; the most common was thromboembolism (three [4%] for gemcitabine plus ramucirumab vs two [2%] for gemcitabine plus placebo). There were no treatment-related deaths.
Interpretation |
Ramucirumab plus gemcitabine significantly improved overall survival after first-line standard chemotherapy, with a favourable safety profile. This combination could be a new option in this setting.
Funding |
Eli Lilly Italy.
Translation |
For the Italian translation of the abstract see Supplementary Materials section.
Le texte complet de cet article est disponible en PDF.Plan
Vol 22 - N° 10
P. 1438-1447 - octobre 2021 Retour au numéro
Article précédent
- Estimating the impact of the COVID-19 pandemic on diagnosis and survival of five cancers in Chile from 2020 to 2030: a simulation-based analysis
- Zachary J Ward, Magdalena Walbaum, Benjamin Walbaum, Maria Jose Guzman, Jorge Jimenez de la Jara, Bruno Nervi, Rifat Atun
- Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery
- Joe Y Chang, Reza J Mehran, Lei Feng, Vivek Verma, Zhongxing Liao, James W Welsh, Steven H Lin, Michael S O’Reilly, Melenda D Jeter, Peter A Balter, Stephen E McRae, Donald Berry, John V Heymach, Jack A Roth, The STARS Lung Cancer Trials Group, Mara Antonoff, Wayne Hofstetter, Ravi Rajaram, David Rice, Boris Sepesi, Stephen Swisher, Ara Vaporciyan, Garrett Walsh, Craig DeGraaf, Arlene Correa, Aileen Chen, Saumil Gandhi, Ritsuko Komaki, Percy Lee, Quynh-Nhu Nguyen, Matthew Ning, Song Gao, Julianne Pollard-Larkin, Paige Nitsch, Ramaswamy Sadagopan, Xiaochun Wang
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?