Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial.

Abstract

4008 Background: Organ preservation (OP) with a watch and wait strategy (WW) and total neoadjuvant therapy (TNT) are new treatment paradigms for patients with locally advanced rectal cancer. The safety and efficacy of WW and of TNT have not been studied prospectively. Methods: Patients with MRI stage II and III rectal adenocarcinoma were randomized to 4 months of FOLFOX or CAPEOX before (Induction) or after (Consolidation) fluorouracil or capecitabine based chemoradiotherapy (CRT). Patients were re-staged 8-12 weeks after finishing TNT with digital rectal exam, flexible sigmoidoscopy and MRI. Patients with complete or near-complete clinical response were offered WW. Those with incomplete response had total mesorectal excision. The trial was designed so that each arm served as its own single-stage study that discriminates between 3-year disease-free survival (DFS) rates of 75% (historical null) and 85%, with 86% power, and a two-sided type I error of 5%. Secondary objectives included comparing DFS, OP, and distant metastasis-free survival (DMFS) rates between the two arms using the log-rank test. Results: Of 324 patients enrolled, 307 (152 I, 155 C) are currently evaluable for the time-to-event analysis as of 2/1/2020. Median follow-up is 2.1 years; 52 DFS events were observed. Patient demographics and tumor characteristics were generally balanced across the two arms. Full compliance with systemic chemotherapy was 82% and 81% for the I- and C-arms, respectively. The median radiation dose was 5400 cGy for both arms. Table shows 3-y DFS, DMFS, and OP rates. Conclusions: A WW strategy for patients with locally advanced rectal cancer that achieve a clinical complete response to TNT results in organ preservation for a high proportion of patients without compromising survival. Up-front CRT followed by consolidation chemotherapy resulted in a numerically higher WW rate compared to induction chemotherapy followed by CRT. Clinical trial information: NCT02008656 . [Table: see text]

Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials

“…In fact, a growing amount of evidence questions the added value of TME in patients achieving a pCR. Recently, the results from the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial evaluating this relevant matter have been presented [22]. A total of 324 patients with distal rectal cancer were randomized to two possible TNT strategies, consolidation vs. induction oxaliplatin-based chemotherapy plus CRT.…”

Total Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer

“…[32][33][34][35][36] A list of recent and ongoing TNT trials that are yet to be published is included in eTable 2 in the Supplement. [30][31][32][33][34][35][36][37][38] Identifying predictive biomarkers for patients who are more likely to benefit from TNT is a current need. A National Cancer Database study 39 looked at more than 5000 patients and reported a significantly reduced rate of PCR after neoadjuvant CRT in patients with microsatellite instability (stability vs instability, 8.9% vs 5.9%; OR, 0.65).…”

Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

“…The recently presented OPRA trial sheds some light on this field and gives some possible applications of neoadjuvant chemotherapy [41]. This phase 2 study randomized stage II-III rectal cancer patients to receive four months of induction FOLFOX or CAPOX given before CRT or consolidation FOLFOX or CAPOX given after CRT.…”