The Oncologist 2019 December 24 [Link]
Parikh K, Mandrekar SJ, Allen-Ziegler K, Esplin B, Tan AD, Marchello B, Adjei AA, Molina JR
Preclinical and clinical data have shown promise in using antiangiogenic agents to treat malignant pleural mesothelioma (MPM). We conducted this phase II study to evaluate the efficacy and toxicity of single-agent pazopanib in patients with MPM.
MATERIALS AND METHODS:
Patients with MPM who had received 0-1 prior chemotherapy regimens were eligible to receive pazopanib at a dose of 800 mg daily. The primary endpoint was progression-free survival rate at 6 months (PFS6), with a preplanned interim analysis for futility. Secondary endpoints included overall survival (OS), PFS, adverse events assessment and clinical benefit (complete response, partial response [PR], and stable disease [SD]).
Thirty-four evaluable patients were enrolled, with a median age of 73 years (49-84). The trial was closed early because of lack of efficacy at the preplanned interim analysis. Only 8 patients (28.6%; 95% confidence interval [CI], 13.2-48.7%) in the first 28 evaluable were progression-free at 6 months. PFS6 was 32.4% (95% CI, 17.4-50.5). There were 2 PR (5.9%) and 16 SD (47.1%). The overall median PFS and OS were 4.2 months (95% CI, 2.0-6.0) and 11.5 months (95% CI: 5.3-18.2), respectively. The median PFS and OS for the previously untreated patients was 5.4 months (95% CI, 2.7-8.5) and 16.6 months (95% CI, 6.6-30.6), respectively; and 2.0 months (95% CI, 1.3-4.2) and 5.0 months (95% CI: 3.0-11.9), respectively, for the previously treated patients. Grade 3 or higher adverse events were observed in 23 patients (67.6%).
Single-agent pazopanib was poorly tolerated in patients with MPM. The primary endpoint of PFS6 was not achieved in the current study. ClinicalTrials.gov identification number. NCT00459862.
IMPLICATIONS FOR PRACTICE:
Single-agent pazopanib did not meet its endpoint in this phase II trial in malignant mesothelioma. Pazopanib is well tolerated in mesothelioma patients with a manageable toxicity profile. There is a need to better identify signals of angiogenesis that can be targeted in mesothelioma. Encouraging findings in frontline treatment warrant further investigations in combination with chemotherapy or immunotherapy.