Statistical Validation of the EORTC Prognostic Model for Malignant Pleural Mesothelioma Based on Three Consecutive Phase II Trials

2005 ◽  
Vol 23 (1) ◽  
pp. 184-189 ◽  
Author(s):  
Dean A. Fennell ◽  
Amit Parmar ◽  
Jonathan Shamash ◽  
Marie T. Evans ◽  
Michael T. Sheaff ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Prognostic Model ◽  
Group Performance ◽  
Leukocyte Count ◽  
Low Risk ◽  
Pleural Mesothelioma ◽  
Phase Ii Trials ◽  
Three Phase

Purpose Malignant pleural mesothelioma (MPM) carries a poor prognosis due to chemoresistance. The European Organisation for Research and Treatment of Cancer (EORTC) prognostic model was reported to predict survival in MPM. Our retrospective analysis set out to test the validity of the model as a prognostic tool in patients treated in three phase II trials at St Bartholomew’s Hospital (London, United Kingdom) between 1999 and 2003. Patients and Methods A total of 145 patients were treated in three phase II trials; vinorelbine (VIN; 70 patients), vinorelbine/oxaliplatin (VO; 26 patients), and irinotecan/cisplatin/mitomycin C (IPM; 49 patients). Two subgroups, high-risk and low-risk, were defined by EORTC prognostic score (EPS). EPS was determined by a five-parameter model incorporating age, sex, histology, probability of diagnosis, and leukocyte count. An EPS cutoff of less than 1.27 (low risk) or more than 1.27 (high risk) was used to stratify Kaplan-Meier survival curves. Each of the EPS variables exhibited either trends or significant stratification of overall survival (OS). Results Multivariate analysis confirmed leukocyte count, Eastern Cooperative Oncology Group performance status, and sarcomatous histology as independent prognostic variables. EPS stratified OS in both individual and pooled trial datasets. No association between objective tumor response and EPS classification was identified by multinomial logistic regression. EPS stratified progression-free survival for the VO and IPM cohorts, but not for VIN. Conclusion This study validates the EPS system as a robust tool for stratifying small trials into low- and high-risk subgroups. EPS should facilitate patient selection and analysis in randomized clinical trials.

O-30 Statistical validation of the EORTC prognostic model for malignant pleural mesothelioma based on three consecutive phase II trials

Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S12 ◽  
Author(s):  
Dean A. Fennell ◽  
Amit Parmar ◽  
Jonathan Shamash ◽  
Marie T. Evans ◽  
Richard J. Sylvester ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Prognostic Model ◽  
Pleural Mesothelioma ◽  
Phase Ii Trials ◽  
Statistical Validation ◽  
Consecutive Phase

scholarly journals Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials

2008 ◽  
Vol 99 (1) ◽  
pp. 51-56 ◽  
Author(s):  
G L Ceresoli ◽  
B Castagneto ◽  
P A Zucali ◽  
A Favaretto ◽  
M Mencoboni ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Combined Analysis

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.

Chemotherapy in malignant pleural mesothelioma. A review.

1996 ◽  
Vol 14 (3) ◽  
pp. 1007-1017 ◽  
Author(s):  
S T Ong ◽  
N J Vogelzang
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Single Agent ◽  
High Dose ◽  
Pleural Mesothelioma ◽  
High Dose Methotrexate ◽  
Phase Ii Trials ◽  
Dose Methotrexate

PURPOSE AND DESIGN We reviewed the published literature of clinical studies in malignant pleural mesothelioma, including phase II trials of the newer antifolates and plant derivatives, as well as older single-agent and combination chemotherapy trials. We excluded trials with less than 15 patients, although we have mentioned smaller trials in the text to make a specific point, as well as ones that show promise. We have also included confidence intervals when cited in the original reports, or calculated them when absent. RESULTS No drugs have consistently induced a response greater than 20%. Higher response rates have been reported with detorubicin, high-dose methotrexate, and edatrexate at 26%, 37%, and 25%, respectively, but these have yet to be confirmed. Agents that produce response rates in 10% to 20% of patients include doxorubicin, epirubicin, mitomycin, cyclophosphamide, ifosfamide, cisplatin, and carboplatin. Combination chemotherapy trials do not demonstrate a consistently greater response rate than single-agent trials. However, the combination of doxorubicin, cisplatin, bleomycin, and mitomycin demonstrated a response rate of 44% (95% confidence interval, 27% to 63%), but this remains unconfirmed. Intrapleural therapy using interferon gamma, particularly for small-volume disease, shows promise. CONCLUSION The successful treatment of unresectable pleural mesothelioma awaits the discovery of active drugs. Recent trials of high-dose methotrexate and other antifolates are encouraging. Newer agents, including suramin, should be evaluated in phase II trials. Off-protocol combination therapy cannot be recommended over single-agent therapy, but studies that use combinations of the newer agents should be conducted.

48 Phase II trials of etoposide in malignant pleural mesothelioma

Lung Cancer ◽  
1997 ◽  
Vol 18 ◽  
pp. 15
Author(s):  
T. Sahmoud ◽  
P.E. Postmus ◽  
Ch. van Pottelsberghe ◽  
K. Mattson ◽  
L. Tammilehto ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Phase Ii Trials

scholarly journals Etoposide in malignant pleural mesothelioma: Two phase II trials of the EORTC lung cancer cooperative group

1997 ◽  
Vol 33 (13) ◽  
pp. 2211-2215 ◽  
Author(s):  
T. Sahmoud ◽  
P.E. Postmus ◽  
Ch. van Pottelsberghe ◽  
K. Mattson ◽  
L. Tammilehto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Cooperative Group ◽  
Phase Ii Trials ◽  
Two Phase

Therapies currently in Phase II trials for malignant pleural mesothelioma

2013 ◽  
Vol 22 (10) ◽  
pp. 1255-1263 ◽  
Author(s):  
Giulia Pinton ◽  
Arcangela Gabriella Manente ◽  
Daniela Tavian ◽  
Laura Moro ◽  
Luciano Mutti
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Phase Ii Trials

scholarly journals Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Development and Validation of a Four-Factor Prognostic Model

2020 ◽  
pp. JCO.20.00979 ◽  
Author(s):  
Inhye E. Ahn ◽  
Xin Tian ◽  
David Ipe ◽  
Mei Cheng ◽  
Maher Albitar ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Phase Ii ◽  
Prognostic Model ◽  
Risk Group ◽  
Machine Learning Algorithms ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
Data Set ◽  
Increased Risk

PURPOSE Randomized trials established the superiority of ibrutinib-based therapy over chemoimmunotherapy in chronic lymphocytic leukemia. Durability of progression-free survival (PFS) with ibrutinib can vary by patient subgroup. Clinical tools for prognostication and risk-stratification are needed. PATIENTS AND METHODS Patients treated with ibrutinib in phase II and III trials provided the discovery data set and were subdivided into discovery and internal validation cohorts. An external validation cohort included 84 patients enrolled in our investigator-initiated phase II trial. Univariable analysis of 18 pretreatment parameters was performed using PFS and overall survival (OS) end-points. Multivariable analysis and machine-learning algorithms identified four factors for a prognostic model that was validated in internal and external cohorts. RESULTS Factors independently associated with inferior PFS and OS were as follows: TP53 aberration, prior treatment, β-2 microglobulin ≥ 5 mg/L, and lactate dehydrogenase > 250 U/L. Each of these four factors contributed one point to a prognostic model that stratified patients into three risk groups: three to four points, high risk; two points, intermediate risk; zero to one point, low risk. The 3-year PFS rates for all 804 patients combined were 47%, 74%, and 87% for the high-, the intermediate-, and the low-risk group, respectively ( P < .0001). The 3-year OS rates were 63%, 83%, and 93%, respectively ( P < .0001). The model remained significant when applied to treatment-naïve and relapsed/refractory cohorts individually. For 84 patients in the external cohort, BTK and PLCG2 mutations were tested cross-sectionally and at progression. The cumulative incidences of mutations were strongly correlated with the model. In the external cohort, Richter’s transformation occurred in 17% of the high-risk group, and in no patient in the low-risk group. CONCLUSION Patients at increased risk of ibrutinib failure can be identified at treatment initiation and considered for clinical trials.

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