SWOG S0722

Phase II study of mTOR inhibitor everolimus (RAD001) in advanced Malignant Pleural Mesothelioma (MPM)

Sai Hong Ignatius Ou, James Moon, Linda L. Garland, Philip Mack, Joseph R. Testa, Anne S. Tsao, Antoniette J. Wozniak, David R Gandara

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

INTRODUCTION:: The PI3K/Akt/mammalian target of rapamycin pathway is activated in a majority of malignant pleural mesotheliomas (MPM). We evaluated the activity of everolimus, an oral mammalian target of rapamycin inhibitor, in patients with unresectable MPM. METHODS:: MPM patients who had received at least one but no more than two prior chemotherapy regimens, which must have been platinum-based, were treated with 10 mg of everolimus daily. The primary endpoint was 4-month progression-free survival (PFS) by RECIST 1.1. RESULTS:: A total of 59 evaluable patients were included in the analysis. The median duration of treatment was 2 cycles (56 days). Overall response rate was 2% [95% confidence interval (CI): 0-12%] by RECIST 1.1 and 0% (0-10%) by modified RECIST for MPM. The 4-month PFS rate was 29% (95% CI: 17-41%) by RECIST 1.1, and 27% (95% CI: 16-39%) by modified RECIST. The median PFS was 2.8 months (95% CI: 1.8-3.4) by RECIST 1.1. The median overall survival was 6.3 months (95% CI: 4.0-8.0). There was no difference in PFS among patients who received one or two prior chemotherapy regimens (p = 0.74). There was no difference in overall survival between patients with epithelioid histology versus other types (p = 0.47). The most common toxicities were fatigue (59%), hypertriglyceridemia (44%), anemia (42%), oral mucositis (34%), nausea (32%), and anorexia (32%). The most common grade 3 to 4 toxicities were fatigue (10.2%), anemia (6.8%), and lung infection (6.8%). CONCLUSION:: Everolimus has limited clinical activity in advanced MPM patients. Additional studies of single-agent everolimus in advanced MPM are not warranted.

Original languageEnglish (US)
Pages (from-to)387-391
Number of pages5
JournalJournal of Thoracic Oncology
Volume10
Issue number2
DOIs
StatePublished - Feb 6 2015

Fingerprint

Disease-Free Survival
Confidence Intervals
Sirolimus
Fatigue
Anemia
Drug Therapy
Stomatitis
Survival
Hypertriglyceridemia
Anorexia
Platinum
Phosphatidylinositol 3-Kinases
Nausea
Malignant Mesothelioma
Response Evaluation Criteria in Solid Tumors
Everolimus
Histology
Survival Rate
Lung
Infection

Keywords

  • Everolimus
  • Malignant pleural mesothelioma
  • Modified RECIST
  • mTOR inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

SWOG S0722 : Phase II study of mTOR inhibitor everolimus (RAD001) in advanced Malignant Pleural Mesothelioma (MPM). / Ou, Sai Hong Ignatius; Moon, James; Garland, Linda L.; Mack, Philip; Testa, Joseph R.; Tsao, Anne S.; Wozniak, Antoniette J.; Gandara, David R.

In: Journal of Thoracic Oncology, Vol. 10, No. 2, 06.02.2015, p. 387-391.

Research output: Contribution to journalArticle

Ou, Sai Hong Ignatius ; Moon, James ; Garland, Linda L. ; Mack, Philip ; Testa, Joseph R. ; Tsao, Anne S. ; Wozniak, Antoniette J. ; Gandara, David R. / SWOG S0722 : Phase II study of mTOR inhibitor everolimus (RAD001) in advanced Malignant Pleural Mesothelioma (MPM). In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 2. pp. 387-391.
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AU - Mack, Philip

AU - Testa, Joseph R.

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