Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107)

Our plain-English summary of Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107), by T. Jahan, L. Gu, R. Kratzke, et al (Lung Cancer, 2012).

The study

• Authors: T. Jahan, L. Gu, R. Kratzke, A. Dudek, G.A. Otterson, X. Wang, M. Green, E.E. Vokes, H.L. Kindler
• Journal: Lung Cancer
• Published: 2012;76(3):393-6
• Cited by: 55 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: The Cancer and Leukemia Group B (CALGB) conducted a multi-center phase II trial to evaluate the efficacy and safety of vatalanib in previously untreated patients with malignant mesothelioma and to evaluate potential biomarkers of disease response (CALGB 30107).

Methods: Treatment consisted of vatalanib 1250 mg given orally once daily. CT scans were obtained at baseline and every 6 weeks thereafter. Baseline serum levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), thrombospondin-1 (TSP-1), and mesothelin were obtained. The primary endpoint was 3-month progression-free survival (PFS).

Results: Forty-seven patients enrolled at 19 centers. The median age was 75 years, and the majority of patients (79%) had an ECOG performance status of 1. Tumors were classified as epithelial (77%), sarcomatoid (10%), or mixed (9%) histology. Toxicity was mild; the most common grade 3/4 adverse events were neutropenia (2%), nausea (15%), elevated alanine aminotransferase (11%), hypertension (2%), and gastrointestinal bleeding (2%). Partial responses were observed in 6% of patients and stable disease in 72% of patients. The 3-month PFS rate was 55% (95% CI: 40%, 68%). The median PFS was 4.1 months. Median overall survival was 10.0 months. There was no correlation between serum levels of VEGF, PDGF, TSP-1, or mesothelin and treatment response, PFS, or survival.

Conclusions: Vatalanib as a single agent with this dose and schedule does not warrant further study in this disease.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This phase II trial, run by the Cancer and Leukemia Group B at 19 centers, tested the drug vatalanib in people with malignant mesothelioma who had not previously received systemic chemotherapy. Forty-seven patients enrolled between July 2003 and November 2004; their median age was 75, 91% were men, and 88% had tumors starting in the pleura. Each took 1250 mg of vatalanib by mouth once daily. Asbestos exposure was not studied. Three patients (6.4%, 95% CI 1.3 to 17.5%) had partial tumor shrinkage and 34 (72.3%) had stable disease. At 3 months, 55.3% (95% CI 40.1 to 68.1%) were alive without their disease worsening, short of the trial's 75% target. Median progression-free survival was 4.1 months (95% CI 2.2 to 5.3) and median overall survival 10.0 months (95% CI 6.3 to 14.4). The most common serious non-blood side effects were nausea (15%) and liver-enzyme (ALT) rises (11%). Pre-treatment blood markers showed no significant link to outcomes. The authors concluded that vatalanib alone did not warrant further development, noting twice-daily dosing might have given more favorable results.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: single-arm, multicenter phase II clinical trial of a drug
• Who was studied: 47 patients with malignant mesothelioma at 19 US centers, enrolled July 2003 to November 2004. None had received prior systemic chemotherapy, but prior intrapleural therapy, including bleomycin, was allowed. Median age was 75 and 91% were male. Tumor site was the pleura in 41 (88%), the peritoneum in 3 (6%) and other sites in 3 (6%).
• Exposure: The drug vatalanib, 1250 mg orally once daily in 21-day cycles. Asbestos exposure was not studied. The authors only remarked that the male predominance was consistent with an occupationally induced cancer.
• Main results:
  • 46 patients were evaluable for response. Of these, 3 had a partial response, an objective response rate of 6.4% (95% CI 1.3 to 17.5%). 34 patients (72.3%) had stable disease.
  • The 3-month progression-free survival rate, the primary endpoint, was 55.3% (95% CI 40.1 to 68.1%).
  • Median progression-free survival was 4.1 months (95% CI 2.2 to 5.3).
  • Median overall survival was 10.0 months (95% CI 6.3 to 14.4, printed with a percent sign). The one-year survival rate was 44.7%.
  • All 47 patients were assessed for toxicity. There were no treatment-related deaths (grade 5 events). The most common non-blood grade 3 or 4 events were nausea (15%), vomiting (9%), ALT elevations (11%) and AST elevations (6%).
  • 40 patients had adequate serum samples. In these patients, baseline levels of PDGF, VEGF, TSP-1 and mesothelin showed no significant association with overall or progression-free survival, and none predicted tumor response.
• The authors' conclusion: The authors concluded that further development of vatalanib as a single agent for malignant mesothelioma is not warranted based on this study's findings.
• Limitations the authors state:
  • The authors said that, in retrospect, a 6-month progression-free survival endpoint may have been more clinically meaningful than the 3-month endpoint used.
  • The authors said that later information suggested a dose of at least 1000 mg twice daily is optimal, and that their results might have been more favorable with twice-daily dosing than with the once-daily 1250 mg dose used.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Biomarker, CT Scan, Platelet-Derived Growth Factor (PDGF), Mesothelin, Progression-Free Survival, ECOG Performance Status, Sarcomatoid.

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