In the German phase II PAPGEMO trial reported in JAMA Oncology, Hans-Joachim Schmoll, MD, PhD, and colleagues found that the combination of pazopanib and gemcitabine improved 12-week progression-free survival vs pazopanib alone in patients with anthracycline- or ifosfamide-refractory soft-tissue sarcoma.
Hans-Joachim Schmoll, MD, PhD
The open-label, multicenter trial included 86 evaluable patients with relapse or disease progression after at least one prior treatment with an anthracycline, ifosfamide/trofosfamide, or both. Patients were randomly assigned between September 2011 and July 2014 to receive pazopanib at 800 mg once daily beginning on day 1 of cycle 1 plus gemcitabine at 1,000 mg/m2 on days 1 and 8 of each 21-day cycle (n = 43) or pazopanib alone (control group, n = 43). Treatment was continued until disease progression, intolerable toxicity, or treatment delay of longer than 2 weeks.
The predominant histologic subtypes were leiomyosarcoma (n = 22, 26%; 13 in combination group, 9 in control group) and liposarcoma (n = 16, 19%; 9 in combination group, 7 in control group). The primary endpoint was progression-free survival at 12 weeks.
Median follow-up was 12.4 months (range = 1–48 months). Progression-free survival at 12 weeks was 74% in the pazopanib/gemcitabine group vs 47% in the pazopanib alone group (adjusted relative risk = 1.60, 90% confidence interval [CI] =1.15–2.23, P = .01).
Median progression-free survival was 5.6 vs 2.0 months (hazard ratio [HR] = 0.58, 95% CI = 0.36–0.92, P = .02). Median overall survival was 13.1 vs 11.2 months (HR = 0.98, 95% CI = 0.60–1.58, P = .83). Objective response rates were 11% vs 5% (P = .10).
In subgroup analyses, median progression-free survival was 8.5 vs 3.0 months (HR = 0.41, 95% CI = 0.16–1.07) and median overall survival was 20.2 vs 24.2 months (HR = 1.2, 95% CI = 0.43–3.4) among patients with leiomyosarcoma. Among patients with liposarcoma, median progression-free survival was 8.6 vs 1.5 months (HR = undefined, due to size of difference) and median overall survival was 25.4 vs 5.4 months (HR = 0.39, 95% CI = 0.54–1.87).
Grade 3 or 4 adverse events occurred in 79% vs 57% of patients, with the most common in the combination group being thrombocytopenia (40% vs 0% in control group) and leukopenia (33% vs 2%), both related to gemcitabine. Grade 3 or 4 infections occurred in 12% vs 5%, with febrile neutropenia occurring in one patient in the combination group. Grade 3 or 4 adverse events associated with pazopanib included hypertension (12% vs 5%), liver enzyme elevations (9% vs 7%), and thromboembolic events (5% vs 2%). Fatal adverse events occurred in five patients in the combination group and three in the control group, with two considered related to pazopanib (acute respiratory distress syndrome and general health deterioration, respectively).
The investigators concluded, “This phase II randomized clinical trial of patients with soft-tissue sarcoma found that the addition of gemcitabine to pazopanib was tolerable, and the progression-free survival rate at 12 weeks was significantly higher compared with pazopanib alone. These results suggest clinical activity of the combination, but they should be confirmed in a phase III trial in a more homogeneous population (eg, leiomyosarcoma).”
Dr. Schmoll, of University Clinic, Martin Luther University Halle-Wittenberg, is the corresponding author for the JAMA Oncology article.
Disclosure: The trial was supported by an educational grant from GlaxoSmithKline-Germany. For full disclosures of the study authors, visit jamanetwork.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.