In the Chinese phase III STELLAR trial reported in the Journal of Clinical Oncology, Jin et al found that preoperative short-term radiotherapy followed by chemotherapy was not inferior in 3-year disease-free survival vs a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer.
Study Details
In the open-label multicenter trial, 599 patients were randomly assigned between August 2015 and August 2018 to receive preoperative treatment with either:
- Short-term radiotherapy consisting of 25 Gy in five fractions over 1 week, followed by four cycles of CAPOX (oxaliplatin at 130 mg/m2 on day 1 and capecitabine at 1,000 mg/m2 twice daily from day 1 to day 14 at 7–14 days after completion of radiotherapy [total neoadjuvant therapy]; n = 302)
- Chemoradiotherapy consisting of 50 Gy in 25 fractions over 5 weeks concurrently with capecitabine at 825 mg/m2 twice daily (n = 297).
Postoperative chemotherapy consisted of two cycles of CAPOX in the total neoadjuvant therapy group and six cycles of CAPOX in the chemoradiotherapy group. The primary endpoint was 3-year disease-free survival in the intention-to treat population, with a noninferiority margin of < 1.43 for the upper bound of the confidence interval for the hazard ratio.
Key Findings
Median follow-up was 35.0 months (range = 8.3–63.9 months). Rates of 3-year disease-free survival were 64.5% (95% CI = 58.3%–70.7%) in the total neoadjuvant therapy group vs 62.3% (95% CI = 56.1%–68.5%) in the chemoradiotherapy group (hazard ratio [HR] = 0.883, one-sided 95% confidence interval [CI] = not applicable to 1.11, P < .001 for noninferiority).
No significant differences between groups were observed for 3-year metastasis-free survival (77.1% vs 75.3%, HR = 0.88, 95% CI = 0.63–1.24, P = .475) or locoregional recurrence (8.4% vs 11.0%, HR = 0.80, 95% CI = 0.45–1.44, P = .461). The rate of 3-year overall survival was superior in the total neoadjuvant therapy group (86.5% vs 75.1%, HR = 0.67, 95% CI = 0.46–0.97, P = .033).
Grade 3 or 4 adverse events during preoperative treatment occurred in 26.5% of patients in the total neoadjuvant therapy group vs 12.6% of the chemoradiotherapy group (P < .001), with the most common in the total neoadjuvant therapy group being hematologic adverse events (15.8% vs 2.0%, P < .001).
The investigators concluded, “Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to chemoradiotherapy for locally advanced rectal cancer.”
Jing Jin, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Chinese Academy of Medical Science Innovation Fund for Medical Sciences, National Key Projects of Research and Development of China, and others. For full disclosures of the study authors, visit ascopubs.org.
