KEY TAKEAWAYS
- The UNION phase III study aimed to compare SCRT+immunochemo vs. LCRT+chemo in LARC.
- The primary endpoint was to determine the pCR rate. The secondary endpoint tested 3-year EFS and OS.
- SCRT + CAM and chemotherapy demonstrated superior pCR rates.
As per the derived outcome of phase 2 pre-clinical research and investigation, T. Zhang and her researchers undertook a randomized, multicenter, open-label phase III trial, that aimed to compare two treatment strategies for locally advanced rectal cancer (LARC)): short-course radiotherapy (SCRT) with subsequent immunochemotherapy versus the long-established standard of long-course chemoradiotherapy (LCRT) followed by chemotherapy.
In this interventional study, patients (pts) with T3-4 or N+ rectal adenocarcinoma, where the tumor’s lower edge was ≤ 10 cm from the anal verge, were randomly assigned (1:1 ratio) to Arm A or B. Stratification considered clinical T stage (≤ T3 vs. T4) and N stage (N0 vs. N+). They received SCRT or LCRT, followed by 2 cycles of camrelizumab (CAM) + CAPOX or CAPOX, respectively. Total mesorectal excision (TME) ensued, with an additional 6 cycles of CAM + CAPOX followed by CAM for up to 1 year in Arm A and 6 cycles of CAPOX in Arm B.
The primary endpoint was an independent review committee (IRC)-assessed pCR rate (ypT0N0), and secondary endpoints were hierarchically tested3-year EFS rate and OS.
Among the 231 randomly assigned pts(Arm A: n=113, Arm B: n=118), Arm A had 112 pts. receiving SCRT, with 107 completing neoadjuvant therapy and 104 undergoing TME. In Arm B, 115 pts received LCRT, 109 completed neoadjuvant therapy, and 99 underwent TME.
The IRC-assessed pCR rate in the ITT populations was significantly higher in Arm A (39.8% [95% CI 30.7-49.5]) compared to Arm B (15.3% [95% CI 9.3-23.0]), with an odds ratio of 3.7 (95% CI 2.0-6.9, P<0.001), meeting the primary endpoint.
The subgroup analysis consistently revealed positive results across all subgroups. In the surgical population, the R0 resection rate was 96.2% in Arm A and 97.0% in Arm B. Postoperative complications occurred in 38.1% of pts in Arm A versus 40.8% in Arm B. Grade ≥ 3 TRAEs were observed in 29.2% of pts in Arm A and 27.2% in Arm B throughout treatment. Long-term survival outcomes are currently under monitoring.
The study concluded that superior pCR rates with acceptable tolerance were observed in LARC patients with SCRT followed by CAM and chemotherapy compared to those undergoing LCRT followed by chemotherapy. The study is sponsored by Wuhan Union Hospital, China.
Clinical trial: https://clinicaltrials.gov/study/NCT04928807
Zhang T, Tao K, Lin Z, et al. “LBA25 – Neoadjuvant short-course radiotherapy followed by camrelizumab plus chemotherapy versus long-course chemoradiotherapy followed by chemotherapy in locally advanced rectal cancer: A randomized phase III trial (UNION)” presented at ESMO 2023. Abstract LBA25
