Pazopanib Beneficial for Patients with Previously Treated Metastatic Soft Tissue Sarcoma

Findings of the phase III PALETTE trial reveal that pazopanib, a multitargeted angiogenesis inhibitor, is active against common subtypes of previously treated metastatic soft tissue sarcoma (STS).

Abbreviation: CI, confidence interval.

More specifically, pazopanib monotherapy yielded a 3-fold increase in progression-free survival (PFS) compared with placebo in progressive disease that was previously treated with anthracyclines.

"After decades of chemotherapy, we finally have a new drug against soft tissue sarcomas. I think pazopanib can be added to the pallet of potential active drugs for our patients," said Winette T. A. van der Graaf, MD, PhD, of the Radboud University Medical Center, The Netherlands, who presented the findings of the international PALETTE trial on behalf of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group during the Sarcoma Oral Abstract Session (Abstract LBA10002).

In prior research, pazopanib demonstrated single-agent activity in patients with advanced STS. To expand on these findings, 369 treatment-experienced patients with metastatic STS that progressed within the preceding 6 months were randomly assigned in a double-blind fashion to treatment with pazopanib (246 patients) or to placebo (123 patients), with the primary goal of comparing PFS between the two arms.

Although the study participants had received up to four lines of prior treatment for advanced disease, at least one of which contained an anthracycline, all were required to be naïve to angiogenesis inhibitors for study inclusion.

After a median follow-up of 15 months, the results revealed that pazopanib significantly prolonged PFS by a median of 3.1 months compared with placebo (4.6 vs. 1.5 months, respectively; hazard ratio [HR]: 0.31; 95% CI [0.24, 0.40]; p < 0.0001; Fig. 1).

These PFS benefits were consistently seen across all patient subgroups based on STS histology, including those with leiomyosarcoma (HR: 0.31; 95% CI [0.20, 0.47]; p < 0.0001), synovial sarcoma (HR: 0.19; 95% CI [0.23, 0.60]; p = 0.0002), and other types of sarcoma (HR: 0.36; 95% CI [0.25, 0.52]; p < 0.0001).

An interim analysis showed that improvements in overall survival (OS) paralleled those seen with PFS, reaching 11.9 months for patients who received pazopanib compared with 10.4 months for patients who received placebo, although this 1.5-month difference did not reach statistical significance (p = 0.1782). The final analysis of OS is anticipated late this year and may show a difference between the two arms with longer follow up.

Pazopanib was generally well tolerated, and Dr. van der Graaf stressed that the adverse events associated with pazopanib are manageable with adequate monitoring and timely intervention. Fatigue, diarrhea, and nausea constituted the most common adverse events seen in the pazopanib arm, all occurring in more than one-half of patients.

Notably, grades 3 to 5 thromboembolic events occurred among slightly more patients treated with pazopanib compared with placebo (6 vs. 3 patients), as did grade 3/4 myocardial dysfunction (4 vs. 0 patients). Importantly, one patient receiving pazopanib died from multiorgan failure that was attributed to study therapy.

Discussant Shreyaskumar Patel, MD, of University of Texas M. D. Anderson Cancer Center, noted that pazopanib clearly belongs to a class of compounds with defined activity in STS.

Looking forward, Dr. Patel stated, "it would be quite helpful to enrich the patient population that may benefit from this drug with the help of a biomarker."