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Original Investigation
December 23, 2020

Efficacy of Pazopanib With or Without Gemcitabine in Patients With Anthracycline- and/or Ifosfamide-Refractory Soft Tissue Sarcoma: Final Results of the PAPAGEMO Phase 2 Randomized Clinical Trial

Author Affiliations
  • 1Clinic for Internal Medicine IV–Hematology/Oncology, University Clinic, Martin Luther University, Halle-Wittenberg, Germany
  • 2Department of Medicine III, University Hospital, Ludwig Maximilians University, Munich, Germany
  • 3HELIOS Clinic Berlin Buch, Berlin, Germany
  • 4Paracelsus Medical University, Nuremberg, Germany
  • 5University Hospital Tuebingen, Tuebingen, Germany
  • 6University Hospital Muenster, Muenster, Germany
  • 7University Hospital Ulm, Ulm, Germany
  • 8Department of Internal Medicine V, University Hospital, University of Heidelberg, Heidelberg, Germany
  • 9Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen University, Aachen, Germany
  • 10Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, Mannheim, Germany
  • 11University of Leipzig, Leipzig, Germany
  • 12University Hospital Charité Campus Virchow, Berlin, Germany
  • 13University Hospital Jena, Jena, Germany
  • 14SRH Wald Klinikum, Gera, Germany
  • 15Coordination Center for Clinical Trials Halle, Martin Luther University, Halle-Wittenberg, Germany
  • 16University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
JAMA Oncol. 2021;7(2):255-262. doi:10.1001/jamaoncol.2020.6564
Visual Abstract. Efficacy of Pazopanib With or Without Gemcitabine in Patients With Antracycline- and/or Ifosfamide-Refractory Soft Tissue Sarcoma: Final Results of the Randomized Phase II PAPAGEMO Trial
Efficacy of Pazopanib With or Without Gemcitabine in Patients With Antracycline- and/or Ifosfamide-Refractory Soft Tissue Sarcoma: Final Results of the Randomized Phase II PAPAGEMO Trial
Key Points

Question  What is the tolerability and efficacy of pazopanib and gemcitabine compared with pazopanib alone in pretreated soft tissue sarcoma?

Findings  In this randomized clinical trial with 86 eligible patients, the combination of gemcitabine and pazopanib showed a significantly higher progression-free survival rate at 12 weeks (primary end point) compared with pazopanib alone.

Meaning  The combined regimen of gemcitabine and pazopanib seems to have clinical activity and should be further evaluated.

Abstract

Importance  Pazopanib and gemcitabine have shown good tolerability, albeit modest single-agent activity in pretreated soft tissue sarcoma. A combined regimen to improve outcomes is required.

Objective  To determine the efficacy of gemcitabine and pazopanib compared with pazopanib alone.

Design, Setting, and Participants  This multicenter, randomized phase 2 clinical trial was conducted in Germany from September 2011 to July 2014 and included patients with an Eastern Cooperative Oncology Group performance status score of 0 to 2, adequate organ function, measurable lesion, and progression after at least 1 prior treatment with anthracyclines and/or ifosfamide. Data analysis was performed during 2019 and 2020.

Interventions  Patients were randomized to pazopanib with gemcitabine (A) or without gemcitabine (B).

Main Outcomes and Measures  The primary end point was progression-free survival rate (PFSR) at 12 weeks; secondary end points included toxicity, quality of life, overall survival, and response rates.

Results  A total of 90 patients were randomized, and 86 eligible patients (43 women [50%]) were evaluable, with a median age of 57 (range, 22-84) years and Eastern Cooperative Oncology Group performance status score of 0/1 in 77 participants (90%). The predominant histological subtypes were leiomyosarcoma (22 [26%]) and liposarcoma (16 [19%]). After a median follow-up of 12.4 (range, 1-48) months, the primary end point was met, with a PFSR at 12 weeks of 74% (A) vs 47% (B) (hazard ratio [HR], 1.60; 90% CI, 1.15-2.23; P = .01). In the combination arm, PFSR was significantly longer, with a median of 5.6 vs 2.0 months (HR, 0.58; 95% CI, 0.36-0.92; P = .02) compared with single-agent pazopanib, whereas overall survival was similar, with 13.1 vs 11.2 months (HR, 0.98; 95% CI, 0.60-1.58; P = .83). The objective response rate was overall low, with 11% (A) vs 5% (B) (P = .10). The toxicity of the combination of pazopanib and gemcitabine was increased, but it was manageable and mainly hematological.

Conclusions and Relevance  This phase 2 randomized clinical trial of patients with soft tissue sarcoma found that the addition of gemcitabine to pazopanib was tolerable, and PFSR 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 3 trial in a more homogeneous population (eg, leiomyosarcoma).

Trial Registration  German Clinical Trials Identifier: DRKS00003139

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