Gemcitabine plus pazopanib improves PFS in advanced soft tissue sarcoma

Adding gemcitabine to pazopanib led to a significantly higher progression-free survival (PFS) rate in patients with advanced soft tissue sarcoma compared with pazopanib alone, according to the PAPAGEMO* trial.

The researchers analysed 86 patients (median age 57 years, 50 percent female) with advanced soft tissue sarcoma, of whom 90 percent had an ECOG performance status of 0/1, who were previously treated with anthracyclines and/or ifosfamide. Participants were randomly assigned in a 1:1 ratio to receive either oral pazopanib 800 mg once daily plus intravenous gemcitabine 1,000 mg/m² on days 1 and 8 of each 21-day cycle or pazopanib alone. [JAMA Oncol 2021;7:255-262]

At 12 weeks, patients who received pazopanib plus gemcitabine had a significantly higher PFS rate than those who received pazopanib alone (74.0 percent vs 47.0 percent; adjusted relative risk estimate, 1.60; p=0.01).

Patients treated with pazopanib plus gemcitabine also achieved a significantly longer PFS (median 5.6 vs 2.0 months; hazard ratio [HR], 0.58; p=0.02) and time to progression (median 5.6 vs 2.0 months; HR, 0.57; p=0.02) compared with pazopanib alone.

The overall survival (OS) was comparable between the combination and single-agent arms (median 13.1 vs 11.2 months; HR, 0.98; p=0.83), and this “was likely because of the high rate of subsequent treatment,” the researchers said.

Although relatively low, the objective response rate was at 11.0 percent in the combination arm and only 5.0 percent in the single-agent arm.

In an exploratory analysis of patients with available data on histological subtypes, such as liposarcoma (18.6 percent) and leiomyosarcoma (25.6 percent), those with liposarcoma in the combination arm demonstrated a pronounced effect on PFS (median 8.6 vs 1.5 months) and OS (median 25.4 vs 5.4 months) than the single-agent arm, “although this was limited by the small number of patients (n=16),” noted the researchers.

On the other hand, a similar effect on PFS and OS was observed among patients with leiomyosarcoma between the combination and single-agent arms (median 8.5 vs 3.0 months [PFS] and 20.2 vs 24.2 months [OS]).

Leukopenia (33.0 percent), anaemia (9.0 percent), thrombocytopenia (40.0 percent), and fatigue (7.0 percent) were the most common grade 3/4 adverse events (AEs) reported in the combination arm. Serious AEs with fatal outcome occurred in three patients in the combination arm, while five patients were reported in the single-agent arm.

“The toxicity of the combination of pazopanib and gemcitabine was increased, but it was manageable and mainly haematological,” the researchers noted.

“[Overall,] the addition of gemcitabine to pazopanib was tolerable, … [with] no detrimental effect on quality of life, and [showed that] PFS rate at 12 weeks was significantly higher compared with pazopanib alone,” said the researchers.

[Moreover, the results suggest that] this efficacious combination can be safely administered in an at least second-line sarcoma population,” they added.

*PAPAGEMO: Phase II randomized clinical trial of pazopanib alone and pazopanib plus gemcitabine in relapsed or metastatic soft tissue sarcoma