Activity of Cabazitaxel in Metastatic or Inoperable Locally Advanced Dedifferentiated Liposarcoma

Abstract

ImportanceTreatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. New drugs are required.ObjectiveTo assess whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DDLPS to justify further investigation in a phase 3 setting.Design, Setting, and ParticipantsThis international multicenter, open-label single-arm phase 2 trial was conducted at 10 institutions in 4 European countries from March 2015 to March 2019. Eligible patients had to have metastatic or locally advanced histologically proven DDLPS with evidence of disease progression within the past 6 months and had to have received no more than 1 previous line of chemotherapy.InterventionsAfter mandatory central review of tumor blocks, if the DDLPS diagnosis was confirmed, patients started treatment within 72 hours after registration. Cabazitaxel was administered at a dose of 25 mg/m2 IV infusion over 1 hour every 21 days until intolerance, progression, or withdrawal of consent.Main Outcomes and MeasuresThe primary end point was progression-free survival (PFS) rate at 12 weeks per RECIST 1.1. Based on a Simon 2-stage design, at least 4 of 17 (stage 1) and 11 of 37 (stage 2) eligible and evaluable patients who were progression free at 12 weeks were needed. The final analysis report was completed on November 17, 2021.ResultsForty patients were registered, with 2 patients being ineligible. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. Progression-free survival at 12 weeks was 55%, achieving the primary study end point. At a median follow-up of 21.6 months, median PFS was 6 months and median OS 21 months. Response rate (RR) was 8% with 1 clinical response (CR) and 2 partial responses (PR). Twenty-three (60.5%) patients had a stable disease (SD). Disease control (PR+SD) was achieved in 26 patients (68%).Conclusions and RelevanceThis nonrandomized phase 2 clinical trial met its primary end point, with 21 of 38 patients (55%) being progression free at 12 weeks. These results suggest important activity of cabazitaxel in patients with metastatic or inoperable locally advanced DDLPS. The drug is worth being further studied in these tumors in a phase 3 setting.

Optimizing Histology-Specific Clinical Trials in Soft-Tissue Sarcoma—Are We There Yet?

“…The early data from the current study demonstrate comparable (if not slightly better) PFS compared with recent, liposarcoma-specific trials that led to FDA approvals. In the phase 3 trial of trabectedin vs dacarbazine, the 12-week PFS rates were 56% in the trabectedin arm compared with 34% in the dacarbazine arm, but there was no difference in overall survival.…”

“…In this issue of JAMA Oncology , Sanfilippo and colleagues present the results of an international multicenter, open-label, single-arm phase 2 trial conducted in 10 EORTC (European Organisation for Research and Treatment of Cancer) institutions to evaluate the antitumor activity (defined as progression-free survival [PFS] rate at 12 weeks) of cabazitaxel, a microtubule inhibitor, in patients with locally advanced or metastatic dedifferentiated liposarcoma treated with no more than 1 previous line of chemotherapy. The trial enrolled 38 patients over 48 months and at a median follow-up of 21.6 months; 21 of 37 (55%) were progression free 12 weeks after the start of cabazitaxel treatment, meeting its primary end point (40% PFS at 12 weeks).…”

“…Over the last decade, the importance of histologic subtype in the biology and prognosis of patients with soft-tissue sarcoma has become increasingly recognized. As was done in the current study by Sanfilippo et al, the development and completion of smaller, histology-specific phase 2 trials, which provide strong background data for future phase 3 trials, has led to numerous histology-specific US Food and Drug Administration (FDA) approvals over the last 10 years, a stark contrast to the preceding decades.…”

“…However, completion of the current trial was not a foregone conclusion, and the EORTC Soft Tissue and Bone Sarcoma Group were faced with challenges that are frequently encountered in sarcoma clinical trials. Originally designed as a 2-arm parallel trial evaluating cabazitaxel in one arm and prolonged infusional ifosfamide in a separate arm, the trial was amended in 2016 (2 years after activation) to its current version owing to low accrual, with the expectation that the amended protocol would attract more patients.…”

What’s New in Musculoskeletal Tumor Surgery

“…However, there was no significant difference in overall survival between the 2 treatment groups. In a Phase-2 study by Sanfilippo et al, cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma had an objective response rate of 11.1% and disease control rate of 83.3% 48 . The median progression-free survival was 4.5 months, and the median overall survival was 15.8 months.…”