scholarly journals Nivolumab In Combination With Ipilimumab (Opdivo-Yervoy)

2021 ◽  
Vol 1 (8) ◽  
Author(s):  
Reimbursement Team
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Systemic Treatment ◽  
Performance Status ◽  
Pleural Mesothelioma ◽  
Good Performance Status ◽  
The Cost ◽  
Public Drug

CADTH recommends that Opdivo in combination with Yervoy (nivolumab plus ipilimumab) should be reimbursed by public drug plans for the treatment of malignant pleural mesothelioma (MPM) if certain conditions are met. Opdivo plus Yervoy should only be reimbursed if prescribed by clinicians with experience in immuno-oncology and treating MPM and if the cost of Opdivo plus Yervoy is reduced. Opdivo plus Yervoy should only be covered to treat patients who have not received prior systemic treatment for MPM and who have good performance status at the start of treatment.

scholarly journals Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Mathieu D. Saint-Pierre ◽  
Christopher Pease ◽  
Hamid Mithoowani ◽  
Tinghua Zhang ◽  
Garth A. Nicholas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Performance Status ◽  
Treatment Modalities ◽  
Pleural Mesothelioma ◽  
Cox Models ◽  
Platinum Based Chemotherapy ◽  
Before And After ◽  
Incremental Improvement

Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P=0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P=0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

scholarly journals Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial

2017 ◽  
Vol 35 (31) ◽  
pp. 3591-3600 ◽  
Author(s):  
Federica Grosso ◽  
Nicola Steele ◽  
Silvia Novello ◽  
Anna K. Nowak ◽  
Sanjay Popat ◽  
...  
Keyword(s):  
Overall Survival ◽  
Placebo Group ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Double Blind

Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory phase III part of the study is ongoing.

A phase II trial of nintedanib in recurrent malignant pleural mesothelioma (MPM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20061-e20061
Author(s):  
Antoinette J. Wozniak ◽  
Bryan J. Schneider ◽  
Gregory Peter Kalemkerian ◽  
Robert Michael Daly ◽  
Wei Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Unmet Need ◽  
Small Subset ◽  
Pleural Mesothelioma ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e20061 Background: Malignant pleural mesothelioma (MPM) is a disease that is resistant to chemotherapy and there remains an unmet need for better therapeutic options. Nintedanib (BIBF 1120) is an oral multikinase inhibitor impacting VEGFR, FGFR, PDGFR, and other kinase activity such as TGFß signaling pathways. VEGF, FGF, and TGFβ are commonly expressed in MPM. We conducted a phase II trial in patients with recurrent MPM after platinum-based chemotherapy. Methods: Patients (pts) with MPM previously treated with platinum-based chemotherapy, performance status (PS) 0-1, adequate organ function, and no contraindications to anti-angiogenic therapy were eligible for treatment. Nintedanib 200 mg twice per day was administered until disease progression or unacceptable toxicity. The primary endpoint was the 4-month progression-free survival (PFS). A two-stage design was used and > 4 pts had to have a PFS of ≥4 months to proceed to the second stage. Results: Twenty pts. were enrolled. The median age was 70 yrs. (32-81), 90% were male, and 80% were PS = 1. The histology was 70% epithelioidal, 5% sarcomatoid, 10% biphasic, and 15% unknown. 15% had prior bevacizumab. The median follow-up is 16.4 mo. A median of 2 treatment cycles (range 1-18) were delivered. There were no responses but 40% had stable disease. The median PFS was 1.8 mo. (95% CI: 1.68, 3.55) and the PFS rate at 4 mo. was 13%. The median OS was 4.2 mo. (95% CI: 2.53, 8.74) and the OS rate at 4 mo. was 55%. Toxicities were usually grade 1-2 and included diarrhea, fatigue, edema, transaminase elevation, anorexia, nausea, vomiting and dyspnea. Conclusions: The activity of nintedanib in previously treated MPM pts. was modest. The trial did not meet the primary PFS endpoint. However, there was a small subset of pts. that had prolonged stable disease for > 4 months thus potentially deriving some clinical benefit from treatment. Supported by Boehringer Ingelheim. Clinical trial information: NCT02568449.

scholarly journals ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma

2020 ◽  
Vol 55 (6) ◽  
pp. 1900953 ◽  
Author(s):  
Arnaud Scherpereel ◽  
Isabelle Opitz ◽  
Thierry Berghmans ◽  
Ioannis Psallidas ◽  
Markus Glatzer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malignant Pleural Mesothelioma ◽  
European Society ◽  
Radical Surgery ◽  
Task Force ◽  
Performance Status ◽  
Clinical Importance ◽  
Poor Performance Status ◽  
Pleural Mesothelioma ◽  
European Respiratory Society

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.

A phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma

2020 ◽  
Author(s):  
Kageaki Watanabe ◽  
Yusuke Okuma ◽  
Shoko Kawai ◽  
Makoto Nagamata ◽  
Yukio Hosomi
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Pleural Mesothelioma ◽  
Previously Treated ◽  
Number Of Treatment

Abstract Background Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next-generation anthracycline that is commonly used to treat lung cancer. We conducted a phase II trial of this drug in patients with previously treated MPM.Methods Eligible patients with MPM having adequate organ function and a performance status of 0–2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1–3 every 3 weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate (ORR). Median progression-free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events (AEs) were evaluated as secondary endpoints.Results This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2–11.2) months, and the median OS was 9.1 (range, 6.2–22.0) months. The median number of treatment cycles was three (range, 2–11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia.Conclusion Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.Trial registration number and date of registrationUMIN000010739, May 16, 2013, retrospectively registered

Clinical characteristics, treatment, and survival outcomes in malignant pleural mesothelioma: A institution experience in Turkey.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18544-e18544 ◽  
Author(s):  
Mehmet Kucukoner ◽  
Muhammed Ali Kaplan ◽  
Ali Inal ◽  
Zuhat Urakcı ◽  
Ozlem Abakay ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Malignant Pleural Mesothelioma ◽  
Performance Status ◽  
Survival Rates ◽  
Treatment Modalities ◽  
Pleural Mesothelioma ◽  
Ecog Performance Status ◽  
Clinicopathologic Characteristics ◽  
Rank Analysis ◽  
Significant Difference

e18544 Background: Malignant pleural mesothelioma (MPM) is a aggressive tumor that causes high mortality. Treatment of MPM remains disappointing, even new approaches are present today. Methods: The present study retrospectively examined the data related to 150 patients with MPM who were examined and treated in our center in Turkey from 2005 to 2012. The aims of this study were; to investigate clinicopathologic characteristics, treatment modalities and potential prognostic factors. Results: There were 87 males (58%) and 63 females (42%), 92 of the patients (61.3%) had an asbestos contact and this contact was generally environmental. Surgical resection (EPP or P/D) was used in 32 patients, 87 patients (58%) received only chemotherapy. The median progression free and overall survival (PFS and OS) for all patients were 10.6 and 14.8 months. There was no statistically significant difference between the patients who received pemetrexed/cisplatin (54 patients) and gemcitabine/cisplatin (28 patients) regimens in terms of the PFS and OS (p=0.145, p=0.244). The comparison between patients who were operated on and those who were not did not reveal any statistical difference in PFS and OS (p=0.416, p=0.095). There was no difference in both PFS and OS rates in comparison of patients who had P/D or EPP (p=0.87, p=0.652). Log rank analysis, ECOG performance status (p=0.018), histology (p<0.001), stage (p<0.001) and leukocytosis (p=0.005) were found to be significant prognostic factors in OS. At multivariate analysis, ECOG performance status (p=0.016), and stage (p<0.001) remained independently associated with OS. Conclusions: In survival analysis revealed significant differences in terms of both the PFS and OS, performance status, histology, stage and leukocytosis. EPP or P / D surgical options did not provide difference in term of survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar.

scholarly journals ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma

2020 ◽  
Vol 58 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Isabelle Opitz ◽  
Arnaud Scherpereel ◽  
Thierry Berghmans ◽  
Ioannis Psallidas ◽  
Markus Glatzer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malignant Pleural Mesothelioma ◽  
European Society ◽  
Radical Surgery ◽  
Task Force ◽  
Performance Status ◽  
Clinical Importance ◽  
Poor Performance Status ◽  
Pleural Mesothelioma ◽  
European Respiratory Society

Abstract The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient’s performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.

Malignant pleural mesothelioma: a disease unaffected by current therapeutic maneuvers.

1988 ◽  
Vol 6 (3) ◽  
pp. 527-535 ◽  
Author(s):  
A S Alberts ◽  
G Falkson ◽  
L Goedhals ◽  
D A Vorobiof ◽  
C A Van der Merwe
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Early Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Treatment Modalities ◽  
Pleural Mesothelioma ◽  
Phase Ii Trials ◽  
Duration Of Symptoms ◽  
Histologic Subtype ◽  
Treatment Groups

From 1965 to 1985, 262 patients with malignant pleural mesothelioma were treated with cytostatics only; radiotherapy (RT); RT and cytostatics; or decortication plus RT plus cytostatics. The median survival (MS) from diagnosis was 9.6 months. This was similar for all comparable treatment groups. In a univariate analysis, significant favorable prognostic factors were good performance status (PS), duration of symptoms greater than 6 months at the time of diagnosis, early stage of disease, white race, and female sex. In a multivariate analysis, PS, race, duration of symptoms, and stage were of significance for a favorable prognosis. Age, pain as first symptom, histologic subtype, and RT dose were not of prognosis significance in this study. The stepwise addition of treatment modalities did not increase survival, which remained the same as that reported for untreated patients. Therefore, phase II trials of new agents offer the only hope for advance in the treatment of this disease.

Phase I Clinical and Pharmacokinetic Study of Pemetrexed and Carboplatin in Patients With Malignant Pleural Mesothelioma

2002 ◽  
Vol 20 (16) ◽  
pp. 3533-3544 ◽  
Author(s):  
Andy Hughes ◽  
Paula Calvert ◽  
Ashraf Azzabi ◽  
Ruth Plummer ◽  
Rob Johnson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Intravenous Infusion ◽  
Performance Status ◽  
Maximum Tolerated Dose ◽  
World Health ◽  
Pleural Mesothelioma ◽  
Time Curve ◽  
Phase Ii Studies ◽  
Carboplatin Auc

PURPOSE: To determine the maximum tolerated dose (MTD) of pemetrexed and carboplatin given in combination, to derive a recommended dose for phase II studies, and to explore its efficacy. We assessed toxicities and explored the activity of the drug combination exclusively in patients with malignant pleural mesothelioma (MPM). The pharmacokinetics of both agents was investigated. PATIENTS AND METHODS: Twenty-seven patients (23 male, four female) with MPM were treated on five escalating dose levels. Doses ranged from pemetrexed 400 mg/m2 (as a 10-minute intravenous infusion), followed by carboplatin area under the plasma concentration-time curve (AUC) 4 mg/mL·min (as a 30-minute intravenous infusion) to pemetrexed 500 mg/m2, carboplatin AUC 6 mg/mL·min. All patients had a World Health Organization performance status of 1. A total of 163 courses of treatment were administered (median, six; range, one to 10). RESULTS: The main toxicity was hematologic, particularly neutropenia, although this was characteristically short-lived and caused few clinical problems. The MTD was pemetrexed 500 mg/m2, carboplatin AUC 6, because three of the five patients treated at this dose level experienced a dose-limiting toxicity. Eight partial responses (in 25 assessable patients) were observed for a response rate of 32%. Seventy percent of patients noticed an improvement in symptoms, usually (84%) after only two courses. Median time to progression was 305 days, and median survival time was 451 days. CONCLUSION: The MTD was pemetrexed 500 mg/m2 and carboplatin AUC 6 mg/mL·min. The recommended phase II dose of the combination is pemetrexed 500 mg/m2 and carboplatin AUC 5 mg/mL·min. The combination is both active and well tolerated in MPM and deserves further exploration.

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