Pazopanib Efficacy Differs by Sarcoma Subtype in Japanese Study

The tyrosine kinase inhibitor (TKI) pazopanib appeared to have differing effects among different histologic subtypes of soft-tissue sarcoma (STS), according to a new study conducted in Japan. The trial also revealed some adverse events that had not been of concern in a previous large trial.

“STSs are a rare and heterogeneous group of tumors that include more than 50 histologic types,” wrote study authors led by Tomoki Nakamura, MD, PhD, of Mie University Graduate School of Medicine in Tsu, Japan. As many as 30% of STS patients have a local recurrence, and 38% have clinically detectable metastases. “The development of new systemic treatments for patients with STS has been limited in the past few decades.”

Pazopanib, a TKI with activity against VEGFR-1 and other factors, was approved in the United States and in Japan for treatment of STS in 2012. This was based upon results of the PALETTE trial; the new study’s authors undertook the new post-approval analysis because “the efficacy and safety of pazopanib in Japanese patients with advanced STSs remained to be evaluated in a large-scale cohort.”

The new post-marketing trial included 156 patients with relapsed STS, treated for a median of 28.7 weeks with pazopanib. The results were published online ahead of print in Cancer.

Among 125 evaluable patients, there were 13 partial responses (PRs) to the drug, and 74 had stable disease. Four of 12 alveolar soft part sarcoma had a PR, as did three of 30 undifferentiated pleomorphic sarcoma patients, two of 18 synovial sarcoma patients, and four of 27 of other histologic types.

The median progression-free survival (PFS) for all patients was 15.4 weeks, and there were substantial differences between histologic types. The median PFS among 33 liposarcoma patients was 8 weeks, compared with 17.7 weeks in non-liposarcoma patients. In undifferentiated pleomorphic sarcoma patients the median PFS was 15.3 weeks, and in leiomyosarcoma patients it was 18.6 weeks. The median overall survival in the full cohort was 11.2 months, and followed similar patterns according to subtype. In total, 103 patients died of their sarcoma during the trial.

A total of 48 patients experienced a grade 3 or higher adverse events, and the most common such adverse events included hypertension, pneumothorax, and liver disorder. The latter two adverse events, as well as fatigue, were most commonly the cause of treatment discontinuation. The authors noted that the rate of pneumothorax was 9.7% among those with lung metastases, a much higher rate than observed in the PALETTE study (3%).

The authors noted that the trial was still relatively small, and retrospective in nature, limiting the findings. However, they concluded that “pazopanib is a new, tolerable treatment option; however, adverse events, such as pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study, should be taken into consideration.”