Final results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306.

11503 Background: We have previously reported long-term follow-up results of the favorable efficacy of perioperative chemotherapy with adriamycin plus ifosfamide (AI) for high-grade soft tissue sarcomas (STS) (JCOG0304). We have also reported the results of the second interim analysis of a phase II/III trial to confirm the non-inferiority of perioperative gemcitabine plus docetaxel (GD) to AI for high-grade STS (JCOG1306) in 2020 ASCO Annual Meeting. This study was terminated at the preplanned second interim analysis based on the point estimate of hazard ratio (HR) being above the pre-specified allowable HR of 1.61. The estimated 2-year overall survival (OS) was 94.3% (95% confidence interval (CI) 83.4–98.1%) in AI and 91.6% (80.9–96.4%) in GD (HR 2.55, 95% CI 0.80–8.14) in the analysis. We herein report the final results of JCOG1306 at 5-year follow-up. Methods: Patients with operable, FNCLCC grade 2/3 STS primary tumor (T2bN0M0 or anyTN1M0, AJCC 7th edition) or first local recurrent tumor in the extremities or trunk were randomized to AI or GD. Chemotherapy consisted of adriamycin 60 mg/m 2 plus ifosfamide 10 g/m 2 for AI or gemcitabine 1,800 mg/m 2 plus docetaxel 70 mg/m 2 for GD. The treatments were repeated for 3 courses preoperatively and 2 courses postoperatively in a 3-week interval. The primary endpoint in phase III part was OS. Planned sample size was 140 with a one-sided alpha of 0.1, power of 0.7 and a non-inferiority margin of 8% at 3-year OS (HR of 1.61), assuming 3-year OS of AI to be 85% and that of GD as 87%. Results: A total of 143 patients were enrolled between February 2014 and September 2018, and 5-year follow-up has finished in September 2023. Seventy and 73 patients were assigned to AI and GD, respectively, and included in the efficacy analysis. At the final analysis with a median follow-up of 6.0 years, the estimated 5-year OS was 90.0% (95% CI 80.1–95.1%) in AI and 76.1% (64.5–84.4%) in GD (HR 2.67, 95% CI 1.23–5.80). The estimated 5-year progression-free survival was 65.2% (95% CI: 52.7–75.2%) in AI and 57.4% (45.2–67.8%) in GD (HR: 1.33, 95% CI 0.81–2.18). At the 5-year follow-up analysis, there were no treatment-related deaths in both arms. Conclusions: The results of the second interim analysis were confirmed in the final analysis after five-year follow-up, i.e., non-inferiority of GD to AI in terms of OS could not be confirmed. In the perioperative chemotherapy for high-grade STS in the extremities and trunk, AI remains the standard regimen. Clinical trial information: jRCTs031180003 .