ESTRO 2024 - Abstract Book

S1508

Clinical - Lower GI

ESTRO 2024

Final Results of the CAO/ARO/AIO-12 trial – A Generalized Pairwise Comparison

Markus Diefenhardt 1,2 , Daniel Martin 1,3 , Ralf-Dieter Hofheinz 4 , Michael Ghadimi 5 , Claus Rödel 1,2,3 , Maximilian Fleischmann 1 , Emmanouil Fokas 1,2,3 1 Goethe University Frankfurt, University Hospital, Department of Radiotherapy and Oncology, Frankfurt, Germany. 2 Goethe University Frankfurt, Frankfurt Cancer Institute (FCI), Frankfurt, Germany. 3 German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), partner site Frankfurt, Frankfurt, Germany. 4 University Heidelberg, University Hospital Mannheim, Department of Medical Oncology, Mannheim, Germany. 5 University Göttingen, University Medical Center Göttingen, Department of General, Visceral and Pediatric Surgery, Göttingen, Germany

Purpose/Objective:

To report the final results of the randomized phase II CAO/ARO/AIO-12 trial. We compared both treatment arms, induction chemotherapy followed by chemoradiotherapy (arm A) and chemoradiotherapy followed by consolidation chemotherapy (arm B) in a post-hoc analysis using a Generalized Pairwise Comparison approach. Results for toxicity, adherence and response to total neoadjuvant treatment, as well as the results after 36 months follow-up have already been reported 1,2.

Material/Methods:

This secondary analysis included 306 of 311 patients who were recruited between June 2015 and January 2018 and were treated within the CAO/ARO/AIO-12 trial. Trial data was analyzed post-hoc using the Generalized Pairwise Comparison introduced by Marc Buyse 3. By physicians’ choice, the following outcome parameters, ranked as indicated, were analyzed: overall survival (OS), incidence of locoregional recurrence (LR), incidence of distant metastasis (DM), rate of pathological/clinical complete remission (cR), long-term QoL (at least 24 months after randomization) based on EORTC QLQ-30 questions 29 & 30, and incidence of toxicity (≥ grade 2) during follow-up. OS, LR and DM were analyzed as time to event, cR as binary outcome and QoL, respectively toxicity, were analyzed as continuous parameters. Net treatment benefit (NTB) and win ratio referred to Arm B. Analyses were performed using the BuyseTest package in R statistical software.

Results:

306 patients were evaluable (156 in arm A; 150 in arm B). After a median follow-up of 60 months (IQR 58 months – 62 months) for OS, 21 patients in arm A and 23 patients in arm B died (NTB −7.5% [CI 95% −0.23 - 0.09]). 10 LR in arm A and 8 LR in arm B were reported (NTB 0.9% [CI95% −0.23 - 0.10]). In 31 patients in arm A and 32 patients in arm B DM occurred (NTB −1.1% [CI95% −0.25 - 0.10]). A cR after total neoadjuvant treatment was achieved in 32 patients (arm A), respectively 41 patients (arm B) (NTB 4.5% [CI95% −0.22 - 0.16]). Long-term results of quality of life were available in 195 patients (64%) (NTB LQ29 0.2% [CI95% −0.23 – 0.16], NTB LQ30 0.3% [CI95% −0.21 - 0.16]). In 235 patients (77%) ≥ grade 2 toxicity was reported during follow-up surveillance (NTB −1.5% [CI95% −0.23 - 0.14]). Grade 4 toxicity was reported in 8 patients (arm A 3 patients, arm B 5 patients). The Generalized Pairwise Comparison approach did not identify any significant differences between both arms. The net treatment benefit was −4.32% (CI95% −0.23 – 0.14) for patients treated in arm B associated with a win ratio of 0.91 (CI95% 0.618 1.351, (P=0.65).

Conclusion: