The Updated Results for the Phase 3 Study of 5×5 Gy Followed By Chemotherapy in Locally Advanced Rectal Cancer (STELLAR trial)

Abstract

To present updated outcomes for the phase III trial comparing short-course radiotherapy (SCRT) followed by chemotherapy with long-course chemoradiotherapy (LCRT) in locally advanced rectal cancer (LARC). Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinomas staged by MRI, were randomized to either experimental or control group. The experimental group included SCRT (25 Gy/ 5 fractions/ 5 days) followed by 4 courses of CAPOX before surgery, and the control group consisted of preoperative LCRT (50Gy/ 25 fractions/35 days with concurrent capecitabine). Radical resection under TME principles was performed 6-8 weeks after neoadjuvant treatment, then 2 or 6 courses of CAPOX was prescribed as the postoperative adjuvant chemotherapy in experimental or control group, respectively. This is an ongoing trial, of which the initial results had been reported in ASTRO annual meeting 2016, and now this abstract is about updated data and experience. From August 30, 2015 to February 7, 2017, 238 eligible patients from 12 Chinese hospitals were enrolled, and no significant difference could be detected as to age, gender, TN staging, or MRF status between two groups. 170 patients had finished neoadjuvant treatment, of which grade 3+ acute toxicity was observed 20% of patients in experimental group and 4.7% in control group (p=0.002). In experimental group, the incidences of grade 3+ acute toxicity during 5×5 Gy, from end of SCRT to chemotherapy, and during chemotherapy were 0%, 7.1% and 14.1%, respectively. The most common grade 3+ acute toxicities included diarrhea (4.1%), asthenia (2.9%), and anemia (1.2%), most of which were reversible; but one patient in control group died from myocardial infarction. As a whole, full-dose completion of planned neoadjuvant treatment were observed 89.4% and 94.1% of patients in experimental and control group (p=0.493), respectively. For 115 patients who had undergone surgery, R0 resection rates and pCR rates in experimental and control group were 94.9% vs. 83.9% (p=0.054) and 18.6% vs. 5.4% (p=0.029), respectively, and the incidences of surgical complications were similar between two groups (experimental 30.5% vs. control 26.8%; p=0.659), with perineal complications as the majority of them. In addition, there were 10 patients diagnosed as clinical complete response (cCR) after SCRT followed by chemotherapy and they refused to further radical surgery, which contributing to 30.4% of overall CR rate (Including pCR and cCR) in experimental group. The mean time from surgery to the beginning of adjuvant chemotherapy was 54 days (range 28-91 days) in experimental group, which was longer than 43 days (range 23-97 days) in control group, p=0.05. The updated results supported proceeding of STELLAR trial based on acceptable acute toxicity and surgical complications, and high CR rate in patients with SCRT followed by chemotherapy was stable with increasing cases.(ClinicalTrails No. NCT02533271)