Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy

Sophie Papa; Sanjay Popat; Riyaz Shah; A Toby Prevost; Rohit Lal; Blair McLennan; Paul Cane; Loic Lang-Lazdunski; Zaid Viney; Joel T Dunn; Sally Barrington; David Landau; James Spicer

doi:10.1097/JTO.0b013e31828c2b26

Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy

Sophie Papa, Sanjay Popat, Riyaz Shah, A Toby Prevost, Rohit Lal, Blair McLennan, Paul Cane, Loic Lang-Lazdunski, Zaid Viney, Joel T Dunn, Sally Barrington, David Landau, James Spicer

Research output: Contribution to journal › Article › peer-review

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Abstract

INTRODUCTION: The incidence of mesothelioma is rising. First-line cisplatin and pemetrexed confers a survival benefit, with a median progression-free survival (PFS) of 5.7 months. Sorafenib inhibits tyrosine kinases, including receptors for vascular endothelial growth factor, which are implicated in mesothelioma pathogenesis by preclinical and clinical data.

METHODS: Sorafenib, at 400 mg twice daily, was assessed in a single-arm multicenter phase 2 study, using Simon's two-stage design. Eligible patients had received platinum combination chemotherapy earlier. The primary endpoint was PFS at 6 months, with secondary endpoints, including response rate and metabolic response, assessed using fluorodeoxyglucose positron emission tomography. Published reference values for PFS in mesothelioma provide a benchmark for the null hypothesis of 28% progression-free at 6 months, and for moderate or significant clinical activity of 35% or 43% progression-free at 6 months, respectively.

RESULTS: Fifty-three patients (72%) were treated. Most had epithelioid histology. Ninety-three percent of patients had a performance status 0 or 1. Treatment was well tolerated with few grade 3 or 4 toxicities. Median PFS was 5.1 months, with 36% of patients being progression-free at 6 months. Nine percent of patients remained on study beyond 1 year. Changes in fluorodeoxyglucose positron emission tomography parameters did not predict clinical outcome.

CONCLUSIONS: Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. PFS of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.

Original language	English
Pages (from-to)	783-7
Number of pages	5
Journal	Journal of Thoracic Oncology
Volume	8
Issue number	6
DOIs	https://doi.org/10.1097/JTO.0b013e31828c2b26
Publication status	Published - Jun 2013

Keywords

Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Drug Resistance, Neoplasm
Female
Follow-Up Studies
Glutamates
Guanine
Humans
Male
Mesothelioma
Middle Aged
Neoplasm Staging
Niacinamide
Pemetrexed
Phenylurea Compounds
Platinum
Pleural Neoplasms
Prognosis
Protein Kinase Inhibitors
Salvage Therapy
Survival Rate

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/JTO.0b013e31828c2b26

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Papa, S., Popat, S., Shah, R., Prevost, A. T., Lal, R., McLennan, B., Cane, P., Lang-Lazdunski, L., Viney, Z., Dunn, J. T., Barrington, S., Landau, D., & Spicer, J. (2013). Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy. Journal of Thoracic Oncology, 8(6), 783-7. https://doi.org/10.1097/JTO.0b013e31828c2b26

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title = "Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy",

abstract = "INTRODUCTION: The incidence of mesothelioma is rising. First-line cisplatin and pemetrexed confers a survival benefit, with a median progression-free survival (PFS) of 5.7 months. Sorafenib inhibits tyrosine kinases, including receptors for vascular endothelial growth factor, which are implicated in mesothelioma pathogenesis by preclinical and clinical data.METHODS: Sorafenib, at 400 mg twice daily, was assessed in a single-arm multicenter phase 2 study, using Simon's two-stage design. Eligible patients had received platinum combination chemotherapy earlier. The primary endpoint was PFS at 6 months, with secondary endpoints, including response rate and metabolic response, assessed using fluorodeoxyglucose positron emission tomography. Published reference values for PFS in mesothelioma provide a benchmark for the null hypothesis of 28% progression-free at 6 months, and for moderate or significant clinical activity of 35% or 43% progression-free at 6 months, respectively.RESULTS: Fifty-three patients (72%) were treated. Most had epithelioid histology. Ninety-three percent of patients had a performance status 0 or 1. Treatment was well tolerated with few grade 3 or 4 toxicities. Median PFS was 5.1 months, with 36% of patients being progression-free at 6 months. Nine percent of patients remained on study beyond 1 year. Changes in fluorodeoxyglucose positron emission tomography parameters did not predict clinical outcome.CONCLUSIONS: Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. PFS of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.",

keywords = "Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Glutamates, Guanine, Humans, Male, Mesothelioma, Middle Aged, Neoplasm Staging, Niacinamide, Pemetrexed, Phenylurea Compounds, Platinum, Pleural Neoplasms, Prognosis, Protein Kinase Inhibitors, Salvage Therapy, Survival Rate",

author = "Sophie Papa and Sanjay Popat and Riyaz Shah and Prevost, {A Toby} and Rohit Lal and Blair McLennan and Paul Cane and Loic Lang-Lazdunski and Zaid Viney and Dunn, {Joel T} and Sally Barrington and David Landau and James Spicer",

year = "2013",

month = jun,

doi = "10.1097/JTO.0b013e31828c2b26",

language = "English",

volume = "8",

pages = "783--7",

journal = "Journal of Thoracic Oncology",

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number = "6",

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TY - JOUR

T1 - Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy

AU - Papa, Sophie

AU - Popat, Sanjay

AU - Shah, Riyaz

AU - Prevost, A Toby

AU - Lal, Rohit

AU - McLennan, Blair

AU - Cane, Paul

AU - Lang-Lazdunski, Loic

AU - Viney, Zaid

AU - Dunn, Joel T

AU - Barrington, Sally

AU - Landau, David

AU - Spicer, James

PY - 2013/6

Y1 - 2013/6

N2 - INTRODUCTION: The incidence of mesothelioma is rising. First-line cisplatin and pemetrexed confers a survival benefit, with a median progression-free survival (PFS) of 5.7 months. Sorafenib inhibits tyrosine kinases, including receptors for vascular endothelial growth factor, which are implicated in mesothelioma pathogenesis by preclinical and clinical data.METHODS: Sorafenib, at 400 mg twice daily, was assessed in a single-arm multicenter phase 2 study, using Simon's two-stage design. Eligible patients had received platinum combination chemotherapy earlier. The primary endpoint was PFS at 6 months, with secondary endpoints, including response rate and metabolic response, assessed using fluorodeoxyglucose positron emission tomography. Published reference values for PFS in mesothelioma provide a benchmark for the null hypothesis of 28% progression-free at 6 months, and for moderate or significant clinical activity of 35% or 43% progression-free at 6 months, respectively.RESULTS: Fifty-three patients (72%) were treated. Most had epithelioid histology. Ninety-three percent of patients had a performance status 0 or 1. Treatment was well tolerated with few grade 3 or 4 toxicities. Median PFS was 5.1 months, with 36% of patients being progression-free at 6 months. Nine percent of patients remained on study beyond 1 year. Changes in fluorodeoxyglucose positron emission tomography parameters did not predict clinical outcome.CONCLUSIONS: Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. PFS of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.

AB - INTRODUCTION: The incidence of mesothelioma is rising. First-line cisplatin and pemetrexed confers a survival benefit, with a median progression-free survival (PFS) of 5.7 months. Sorafenib inhibits tyrosine kinases, including receptors for vascular endothelial growth factor, which are implicated in mesothelioma pathogenesis by preclinical and clinical data.METHODS: Sorafenib, at 400 mg twice daily, was assessed in a single-arm multicenter phase 2 study, using Simon's two-stage design. Eligible patients had received platinum combination chemotherapy earlier. The primary endpoint was PFS at 6 months, with secondary endpoints, including response rate and metabolic response, assessed using fluorodeoxyglucose positron emission tomography. Published reference values for PFS in mesothelioma provide a benchmark for the null hypothesis of 28% progression-free at 6 months, and for moderate or significant clinical activity of 35% or 43% progression-free at 6 months, respectively.RESULTS: Fifty-three patients (72%) were treated. Most had epithelioid histology. Ninety-three percent of patients had a performance status 0 or 1. Treatment was well tolerated with few grade 3 or 4 toxicities. Median PFS was 5.1 months, with 36% of patients being progression-free at 6 months. Nine percent of patients remained on study beyond 1 year. Changes in fluorodeoxyglucose positron emission tomography parameters did not predict clinical outcome.CONCLUSIONS: Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. PFS of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Drug Resistance, Neoplasm

KW - Female

KW - Follow-Up Studies

KW - Glutamates

KW - Guanine

KW - Humans

KW - Male

KW - Mesothelioma

KW - Middle Aged

KW - Neoplasm Staging

KW - Niacinamide

KW - Pemetrexed

KW - Phenylurea Compounds

KW - Platinum

KW - Pleural Neoplasms

KW - Prognosis

KW - Protein Kinase Inhibitors

KW - Salvage Therapy

KW - Survival Rate

U2 - 10.1097/JTO.0b013e31828c2b26

DO - 10.1097/JTO.0b013e31828c2b26

M3 - Article

C2 - 23571475

SN - 1556-0864

VL - 8

SP - 783

EP - 787

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

IS - 6

ER -

Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy

Abstract

Keywords

UN SDGs

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