Neoadjuvant Compared to Adjuvant Chemotherapy as Part of Trimodality Therapy for Malignant Pleural Mesothelioma

Introduction. Malignant pleural mesothelioma (MPM) is an aggressive cancer arising from pleural mesothelium. Surgery aims to either cure the disease or control the symptoms. Two surgical procedures exist: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). In this systematic review we assess current evidence on safety and efficacy of surgery. Methods. Five electronic databases were reviewed from January 1990 to January 2013. Studies were selected according to a predefined protocol. Primary endpoint was overall survival. Secondary endpoints included quality of life, disease-free survival, disease recurrence, morbidity, and length of hospital stay. Results. Sixteen studies were included. Median survival ranged from 8.1 to 32 months for P/D and from 6.9 to 46.9 months for EPP. Perioperative mortality was 0%–9.8% and 3.2%–12.5%, respectively. Perioperative morbidity was 5.9%–55% for P/D and 10%–82.6% for EPP. Average length of stay was 7 days for P/D and 9 days for EPP. Conclusion. Current evidence cannot definitively answer which procedure (EPP or P/D) is more beneficial in terms of survival and operative risks. This systematic review suggests that surgery in the context of trimodality therapy offers acceptable perioperative outcomes and long-term survival. Centres specialising in MPM management have better results.

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Neoadjuvant versus adjuvant chemotherapy for resectable malignant pleural mesothelioma: An analysis of the National Cancer Database.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e20556 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e20556-e20556

Author(s):

Fernando Espinoza-Mercado ◽

David Berz ◽

Jerald D Borgella ◽

Taryne A Imai ◽

Harmik J Soukiasian

Keyword(s):

Adjuvant Chemotherapy ◽

Malignant Pleural Mesothelioma ◽

Pleural Mesothelioma ◽

National Cancer Database

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Trial in progress: Neoadjuvant immune checkpoint blockade in resectable malignant pleural mesothelioma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps9078 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS9078-TPS9078

Author(s):

Joshua E. Reuss ◽

Boris Sepesi ◽

Christian Diego Rolfo ◽

Marianna Zahurak ◽

Valsamo Anagnostou ◽

...

Keyword(s):

T Cell ◽

Adjuvant Chemotherapy ◽

Malignant Pleural Mesothelioma ◽

Immune Checkpoint ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Stage I ◽

Stopping Rules ◽

Pleural Mesothelioma ◽

Limited Stage

TPS9078 Background: While the role of surgery in limited-stage (stage I-III) malignant pleural mesothelioma (MPM) is controversial, many centers have adopted an aggressive tri-modality approach incorporating (neo)adjuvant chemotherapy, surgical resection and radiotherapy. Despite this, most patients relapse and die from their disease. Immune checkpoint blockade (ICB) has shown promise in advanced MPM, but the mechanisms of response and resistance remain elusive. Improving the mechanistic understanding of ICB in MPM while concurrently optimizing the treatment strategy for limited-stage MPM are two urgent unmet needs. This multicenter multi-arm phase I/II study seeks to evaluate the safety and feasibility of neoadjuvant ICB in resectable MPM, incorporating novel genomic and immunologic analyses to deliver mechanistic insight into the biology of ICB in MPM. Methods: Patients with surgically resectable stage I-III treatment-naïve epithelioid or biphasic MPM receive neoadjuvant treatment with nivolumab every 2 weeks for 3 doses with or without 1 dose of ipilimumab (arm A: nivolumab monotherapy; arm B: nivolumab + ipilimumab). After macroscopic complete resection, patients receive optional investigator-choice adjuvant chemotherapy +/- radiation. Following this, patients will receive up to 1 year of adjuvant nivolumab. Feasibility and safety are co-primary endpoints of this study with feasibility defined by a delay in surgery of ≤24 days from the preplanned surgical date and safety defined by adverse events according to CTCAE v5.0. Bayesian-designed stopping rules have been implemented for feasibility and safety. Secondary endpoints include assessment of pathologic response and radiographic response using RECIST 1.1 for MPM. Correlative analyses will be performed on tissue specimens obtained pre- and post-ICB, as well as blood obtained pre, during, and post-ICB. Key correlates include multiplex immunofluorescence and longitudinal ctDNA assessment. Whole exome sequencing, T-cell receptor sequencing, and the MANAFEST functional neoantigen assay will be utilized to identify neoantigen-specific T-cell clonotypes and track these clonotypes temporally (during/post ICB) and spatially (across immune compartments). Single-cell RNA sequencing will be used to characterize the functionality of expanded T-cell clonotypes. Accrual to arm B will commence following complete accrual to arm A with a planned total enrollment of 30 patients. This study is open with 1 patient enrolled at the time of submission. Clinical trial information: NCT03918252.

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333 Combined treatment of malignant pleural mesothelioma (MPM): Surgical resection and adjuvant chemotherapy

Lung Cancer ◽

10.1016/s0169-5002(97)89714-0 ◽

1997 ◽

Vol 18 ◽

pp. 85-86

Author(s):

A. Gasparo ◽

T. Testa ◽

M.A. Nahum ◽

E. Spinelli ◽

E. DeBernardis ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Surgical Resection ◽

Malignant Pleural Mesothelioma ◽

Combined Treatment ◽

Pleural Mesothelioma

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miR-625-3p and lncRNA GAS5 in Liquid Biopsies for Predicting the Outcome of Malignant Pleural Mesothelioma Patients Treated with Neo-Adjuvant Chemotherapy and Surgery

Non-Coding RNA ◽

10.3390/ncrna5020041 ◽

2019 ◽

Vol 5 (2) ◽

pp. 41 ◽

Cited By ~ 2

Author(s):

Jelena Kresoja-Rakic ◽

Adam Szpechcinski ◽

Michaela B. Kirschner ◽

Manuel Ronner ◽

Brenda Minatel ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Malignant Pleural Mesothelioma ◽

Progression Free Survival ◽

Rna Degradation ◽

Exploratory Analysis ◽

Pleural Mesothelioma ◽

Liquid Biopsies ◽

Before And After ◽

Neo Adjuvant Chemotherapy ◽

Lncrna Gas5

Combining neo-adjuvant chemotherapy and surgery is part of multimodality treatment of malignant pleural mesothelioma (MPM), but not all patients benefit from this approach. In this exploratory analysis, we investigated the prognostic value of circulating miR-625-3p and lncRNA GAS5 after neo-adjuvant chemotherapy. 36 MPM patients from the SAKK 17/04 trial (NCT00334594), whose blood was available before and after chemotherapy were investigated. RNA was isolated from plasma and reverse transcribed into cDNA. miR-16-5p and β-actin were used as a reference gene for miR-625-3p and GAS5, respectively. After exclusion of samples due to hemolysis or RNA degradation, paired plasma samples from 32 patients before and after chemotherapy were further analyzed. Quantification of miR-625-3p levels in all 64 samples revealed a bimodal distribution and cloning and sequencing of miR-625-3p qPCR product revealed the presence of miR-625-3p isomiRs. Relative change of the circulating miR-625-3p and GAS5 levels after chemotherapy showed that increased circulating miR-625-3p and decreased GAS5 was significantly associated with disease progression (Fisher’s test, p = 0.0393). In addition, decreased levels of circulating GAS5 were significantly associated with shorter overall and progression-free survival. Our exploratory analysis revealed a potential value of circulating non-coding RNA for selection of patients likely to benefit from surgery after platinum-based adjuvant chemotherapy.

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Long-Term Survival Outcomes of Cancer-Directed Surgery for Malignant Pleural Mesothelioma: Propensity Score Matching Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2017.73.8401 ◽

2017 ◽

Vol 35 (29) ◽

pp. 3354-3362 ◽

Cited By ~ 45

Author(s):

David B. Nelson ◽

David C. Rice ◽

Jiangong Niu ◽

Scott Atay ◽

Ara A. Vaporciyan ◽

...

Keyword(s):

Radiation Therapy ◽

Propensity Score ◽

Propensity Score Matching ◽

Median Survival ◽

Malignant Pleural Mesothelioma ◽

Hazard Ratio ◽

Multimodality Therapy ◽

Pleural Mesothelioma ◽

National Cancer Database ◽

Trimodality Therapy

Purpose Small observational studies have shown a survival advantage to undergoing cancer-directed surgery for malignant pleural mesothelioma (MPM); however, it is unclear if these results are generalizable. Our purpose was to evaluate survival after treatment of MPM with cancer-directed surgery and to explore the effect surgery interaction with chemotherapy or radiation therapy on survival by using the National Cancer Database. Patients and Methods Patients with microscopically proven MPM were identified within the National Cancer Database (2004 to 2014). Propensity score matching was performed 1:2 and among this cohort, a Cox proportional hazards regression model was used to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. Results Of 20,561 patients with MPM, 6,645 were identified in the matched cohort, among whom 2,166 underwent no therapy, 2,015 underwent chemotherapy alone, 850 underwent cancer-directed surgery alone, 988 underwent surgery with chemotherapy, and 274 underwent trimodality therapy. The remaining 352 patients underwent another combination of surgery, radiation, or chemotherapy. Thirty-day and 90-day mortality rates were 6.3% and 15.5%. Cancer-directed surgery, chemotherapy, and radiation therapy were independently associated with improved survival (hazard ratio, 0.77, 0.74, and 0.88, respectively). Stratified analysis revealed that surgery-based multimodality therapy demonstrated an improved survival compared with surgery alone, with no significant difference between surgery-based multimodality therapies; however, the largest estimated effect was when cancer-directed surgery, chemotherapy, and radiation therapy were combined (hazard ratio, 0.52). For patients with the epithelial subtype who underwent trimodality therapy, median survival was extended from 14.5 months to 23.4 months. Conclusion MPM is an aggressive and rapidly fatal disease. Surgery-based multimodality therapy was associated with improved survival and may offer therapeutic benefit among carefully selected patients.

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