Pegylated Liposomal Doxorubicin Combined with Ifosfamide for Treating Advanced or Metastatic Soft-tissue Sarcoma: A Prospective, Single-arm Phase II

Purpose: This prospective single-arm phase II clinical trial aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) as the first-line treatment for patients with advanced or metastatic soft-tissue sarcoma (STS). Patients and Methods: Patients received PLD (30 mg/m(2); day 1) in combination with IFO (1.8 g/m(2); days 1-5) every 21 days until disease progression, unacceptable toxicities, patient death, or for up to six cycles. The primary endpoint was progression-free survival (PFS; NCT03268772). Results: Overall, 69 patients with chemotherapy-naive advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival ( OS) were found to be 7.3 [95% confidence interval (CI): 5.7-8.9] and 20.6 (95% CI: 16.3-25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3- 4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (P = 0.669). Exploratory biomarker analysis suggested NF1 singlenucleotide variant was associated with poor OS (P < 0.0001) and PFS (P = 0.044). In addition, 2 patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (P = 0.0056). Conclusions: Combination therapy comprising PLD and IFO is an effective and well-tolerated first-line treatment for patients with advanced or metastatic STS.

Automated summary

This study aimed to evaluate the safety and efficacy of combining pegylated liposomal doxorubicin (PLD) and ifosfamide (IFO) as the first-line treatment for advanced or metastatic soft-tissue sarcoma (STS). The results showed that the combination therapy of PLD and IFO is effective and well-tolerated in treating STS.