Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: Subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072

Annals of Oncology (Impact Factor: 7.04). 02/2014; 25(3). DOI: 10.1093/annonc/mdt586
Source: PubMed


Pazopanib recently received approval for the treatment of certain soft tissue sarcoma (STS) subtypes. We conducted a retrospective analysis on pooled data from two EORTC trials on pazopanib in STS in order to characterize long-term responders and survivors.
Selected patients were treated with pazopanib in phase II (n = 118) and phase III study (PALETTE) (n = 226). Combined median progression-free survival (PFS) was 4.4 months; the median overall survival (OS) was 11.7 months. Thirty-six percent of patients had a PFS ≥ 6 months and were defined as long-term responders; 34% of patients survived ≥18 months, defined as long-term survivors. Patient characteristics were studied for their association with long-term outcomes.
The median follow-up was 2.3 years. Patient characteristics were compared among four subgroups based on short-/long-term PFS and OS, respectively. Seventy-six patients (22.1%) were both long-term responders and long-term survivors. The analysis confirmed the importance of known prognostic factors in metastatic STS patients treated with systemic treatment, such as performance status and tumor grading, and additionally hemoglobin at baseline as new prognostic factor. We identified 12 patients (3.5%) remaining on pazopanib for more than 2 years: nine aged younger than 50 years, nine females, four with smooth muscle tumors and nine with low or intermediate grade tumors at initial diagnosis. The median time on pazopanib in these patients was 2.4 years with the longest duration of 3.7 years.
Thirty-six percent and 34% of all STS patients who received pazopanib in these studies had a long PFS and/or OS, respectively. For more than 2 years, 3.5% of patients remained progression free under pazopanib. Good performance status, low/intermediate grade of the primary tumor and a normal hemoglobin level at baseline were advantageous for long-term outcome. NCT00297258 (phase II) and NCT00753688 (phase III, PALETTE).

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Available from: Jaap Verweij, Aug 04, 2015
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    • "However, the efficacy of pazopanib in specific types of STS, especially hemangiopericytoma, is unknown. A recent subgroup analysis reported that four of seven patients with solitary fibrous tumors exhibited longer-term PFS and OS with pazopanib treatment [25,26]. "
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    ABSTRACT: Hemangiopericytoma is a rare disease entity of soft-tissue sarcoma (STS) that can be cured with surgical resection. In cases of inoperable recurrence or metastasis, palliative chemotherapy is indicated, though there is currently no approved chemotherapy regimen. Therefore new treatment regimens are needed. We describe three cases of metastatic hemangiopericytoma. In the first case, five lines of chemotherapeutic agents were used unsuccessfully in a patient with a 12-year history of metastatic hemangiopericytoma. After one cycle of pazopanib therapy, however, chest radiography showed a decrease in tumor volume of more than 30%. A marked decrease in FDG uptake on PET CT was also noted, and the patient is now on her 5th month of pazopanib therapy. The second case is a patient with a brain hemangiopericytoma with multiple liver, lung, and bone metastases. Pazopanib induced radiologic stabilization of metastatic disease over the course of 8 months. The third case is a patient with a retroperitoneal hemangiopericytoma with pleural and peri-renal metastases. For more than 8 months, he has exhibited stable disease with pazopanib treatment. Pazopanib may be useful for treatment of metastatic hemangiopericytoma, though further studies are needed to confirm the efficacy of this medication and to investigate its molecular mechanism of action.
    Full-text · Article · Sep 2014
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    • "[6]. Patients who had the best chance to benefit with a long survival were those with a good performance status, low or intermediate tumor grade and a normal haemoglobin level at baseline [7]. No differences were recorded according to histology (P = 0.61). "
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    ABSTRACT: Background We retrospectively reviewed data from nine pre-treated metastatic desmoplastic small round cell tumour (DSRCT) patients who received pazopanib. Patients and methods Three patients received pazopanib within the EORTC phase II 62043, three in the EORTC phase III 62072, and three in the context of UK named patient program. Results Nine patients were retrieved from the databases, the median age was 30 years (range: 21–47), they were all males. All had received prior chemotherapy. At the time of treatment start, 4 patients (44%) had ECOG PS 0, 4 (44%) PS 1, 1 (11%) PS 2. Best response was partial response (PR) in 2/9 (22%) patients, stable disease (SD) in 5/9 (56%) and progressive disease (PD) in 2/9 (22%) with a clinical benefit rate (PR + SD > 12 weeks) of 78%. Median PFS and OS were 9.2 (95%CI: 0–23.2) and 15.4 (95%CI: 1.5-29.3) months respectively. With a median follow-up of 20 months, 2/9 (22%) patients are still alive, all progressed. The most common toxicities included neutropenia (G1-2 45%; G3-4 11%), anaemia (G1-2 45%), fatigue (G1-2 67%), diarrhoea (G1-2 45%; G3-4 11%), nausea (G1-2 45%), hypertension (G1-2 45%) and increase in liver enzymes (G1-2 34%; G3-4 11%). Three patients (34%) required a dose reduction. One of the patients discontinued treatment because of persistent increase in total bilirubin level, one due to patient’s choice. Conclusion In this series, pazopanib showed interesting activity in DSRCT patients who progressed after prior chemotherapy without major toxicity.
    Full-text · Article · Jul 2014
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