CHICAGO—Combined therapy with gemcitabine and pazopanib appears to be a viable treatment option for patients with soft-tissue sarcomas refractory to anthracycline or ifosfamide, according to results from a randomized phase II trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 11004).
“The PAPAGEMO trial meets its primary endpoint of a significant improvement of the PFS [progression-free survival] rate at 12 weeks,” reported lead study author Hans-Joachim Schmoll, MD, PhD, of Martin Luther University Halle-Wittenberg in Halle, Germany.
Improved PFS was mainly attributable to effects in patients with liposarcoma and, to a lesser extent, leiomyosarcoma, Schmoll said. However, the improvements noted in subgroup analyses were “only borderline or not significant,” due to the small sample sizes of patients.
Previous research has shown that the VEGF- , PDGF- , and c-kit–targeting tyrosine kinase inhibitor pazopanib significantly increases PFS compared with placebo among patients with soft-tissue sarcomas. Because pazopanib toxicity profiles do not overlap with cytotoxic drugs, combination therapy is an “interesting option” for these patients, Schmoll said.
Gemcitabine demonstrates efficacy and is associated with prolonged PFS in patients whose soft-tissue sarcomas are refractory to anthracycline/ifosfamide therapy. The study authors therefore conducted the randomized, multicenter, open-label, prospective, phase II PAPAGEMO trial to study outcomes associated with pazopanib with or without gemcitabine among patients with refractory soft-tissue sarcoma.
A total of 86 evaluable patients were randomized 1:1 to receive pazopanib (800 mg/d orally) with or without gemcitabine (1,000 mg/m2).
At 12 weeks, PFS was superior for patients in the combination-regimen group (74% vs 55%; P = .006), and median PFS was 5.6 months vs 2.0 months (hazard ratio [HR], 0.58 [95% CI, 0.36–0.92]; P = .02).
Overall survival (OS) was not different between the study groups in the overall analysis or subgroup analyses, probably because of post-trial crossover to gemcitabine among patients in the control (pazopanib only) arm.
Toxicities were more common among patients receiving the combination regimen. Treatment-related serious adverse events occurred in 54% of patients in the combination-therapy group and 16.3% of the control group. Two patient deaths occurred in the combination-therapy group and none in the pazopanib-only group.