Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial

Pinto, Carmine; Zucali, Paolo Andrea; Pagano, Maria; Grosso, Federica; Pasello, Giulia; Garassino, Marina Chiara; Tiseo, Marcello; Parra, Héctor Soto; Grossi, Francesco; Cappuzzo, Federico; Marinis, Filippo de; Pedrazzoli, Paolo; Bonomi, Maria; Gianoncelli, Letizia; Perrino, Matteo; Santoro, Armando; Zanelli, Francesca; Bonelli, Candida; Maconi, Antonio; Frega, Stefano; Gervasi, Erika; Boni, Luca; Ceresoli, Giovanni Luca

doi:10.1016/s1470-2045(21)00404-6

Cited by 55 publications

(49 citation statements)

References 29 publications

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“…PM is indeed a very difficult-to-treat disease with limited treatment options despite recent approaches modulating the tumor microenvironment having shown improvements in survival. The addition of antiangiogenic agents to standard chemotherapy extended overall survival both in first- and in second-line chemotherapy [ 21 , 22 ], and more recently, the association of ipilimumab and nivolumab (CheckMate 743) significantly prolonged overall survival, especially in the non-ePM subtype [ 12 ]. A larger number of PM cases and mechanistic studies is required to validate and understand B cell functioning in this context.…”

Section: Discussionmentioning

confidence: 99%

Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study

Mannarino

Paracchini

Pezzuto

et al. 2022

IJMS

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Pleural mesothelioma (PM) is an aggressive tumor with few therapeutic options. Although patients with epithelioid PM (ePM) survive longer than non-epithelioid PM (non-ePM), heterogeneity of tumor response in ePM is observed. The role of the tumor immune microenvironment (TIME) in the development and progression of PM is currently considered a promising biomarker. A few studies have used high-throughput technologies correlated with TIME evaluation and morphologic and clinical data. This study aimed to identify different morphological, immunohistochemical, and transcriptional profiles that could potentially predict the outcome. A retrospective multicenter cohort of 129 chemonaive PM patients was recruited. Tissue slides were reviewed by dedicated pathologists for histotype classification and immunophenotype of tumor-infiltrating lymphocytes (TILs) and lymphoid aggregates or tertiary lymphoid structures (TLS). ePM (n = 99) survivors were further classified into long (>36 months) or short (<12 months) survivors. RNAseq was performed on a subset of 69 samples. Distinct transcriptional profiling in long and short ePM survivors was found. An inflammatory background with a higher number of B lymphocytes and a prevalence of TLS formations were detected in long compared to short ePM survivors. These results suggest that B cell infiltration could be important in modulating disease aggressiveness, opening a pathway for novel immunotherapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study

Mannarino

Paracchini

Pezzuto

et al. 2022

IJMS

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“…The RAMES positive randomised phase II study, compared gemcitabine with or without ramicirumab in the relapsed setting, with evidence of a doubling of PFS and improved overall survival (HR 0.71 p = 0.028). 16 The phase III trial CONFIRM recently reported a significant improvement in progression-free and overall survival in the relapsed setting, comparing nivolumab with placebo (HRs 0.61, p = 0.001 and 0.71, p = 0.02, respectively). 17 This was the first phase III trial to show improved survival in the relapsed setting.…”

Section: Discussionmentioning

confidence: 99%

Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial

Fennell

Porter

Lester³

et al. 2022

eClinicalMedicine

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“…The Italian RAMES trial compared gemcitabine with or without ramucirumab in patients who had progressed during or after first-line platin and pemetrexed. The combination treatment resulted in a significant improvement in OS (13.8 vs. 7.5 months, HR 0.71) and PFS (6.2 vs. 3.3 months) [ 129 ]. The VIM trial, for the first time, showed PFS benefit of vinorelbine plus active symptom control (ASC) over ASC only.…”

Section: Systemic Treatmentmentioning

confidence: 99%

Current Management and Future Perspective in Pleural Mesothelioma

Shah

Klotz

Glade

2022

Cancers

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Pleural mesothelioma is an aggressive malignancy arising from pleural mesothelial cell lining, predominantly associated with prior exposure to asbestos. The ban on asbestos use has led to its lower incidence in many countries, but globally the disease burden is expected to rise. Therefore, well-planned research is needed to develop more effective, tolerable and affordable drugs. The development of novel treatment has been too slow, with only two regimens of systemic therapy with robust phase 3 data approved formally to date. The treatment scenario for resectable disease remains controversial. However, recent developments in the understanding of disease and clinical trials have been encouraging, and may add better treatment options in the coming years. In this review, we discuss the current treatment options for pleural mesothelioma and shed light on some recent studies and ongoing trials.

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Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial

Cited by 55 publications

References 29 publications

Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study

Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study

Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial

Current Management and Future Perspective in Pleural Mesothelioma

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