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Session Item

Sunday
August 29
10:30 - 11:30
Plenary
Proffered papers 16: Late-breaking abstracts
Anna Kirby, United Kingdom;
Umberto Ricardi, Italy
Proffered papers
Clinical
11:10 - 11:20
TNT in rectal cancer: Final results of the CAO/ARO/AIO-12 randomized phase 2 trial
Emmanouil Fokas, Germany
OC-0293

Abstract

TNT in rectal cancer: Final results of the CAO/ARO/AIO-12 randomized phase 2 trial
Authors:

Emmanouil Fokas1, Anke Schlenska-Lange2, Bülent Polat3, Gunther Klautke4, Rainer Fietkau5, Thomas Kuhnt6, Thomas Brunner7, Ana-Ligia Grosu8, Simon Kirste8, Michael Flentje9, Christoph-Thomas Germer10, Wolf Bechstein11, Tim Friede12, Ralf-Dieter Hofheinz13, Michael Ghadimi14, Claus Rödel15

1University of Frankfurt, Department of Radiotherapy and Oncology, Frankfurt, Germany; 2 Barmherzige Brüder Hospital Regensburg, Department of Haematology and Oncology, Regensburg, Germany; 3 University of Würzburg, Department of Radiation Oncology, Würzburg, Germany; 4DiaCura & Klinikum Coburg, Department of Radiation Oncology and Radiotherapy, Coburg, Germany; 5University of Erlangen-Nürnberg, Department of Radiation Therapy, Erlangen, Germany; 6University of Leipzig, Department of Radiation Therapy, Leipzig, Germany; 7University of Magdeburg, Department of Radiation Therapy, Magdeburg, Germany; 8Medical Center University of Freiburg, Faculty of Medicine, Freiburg, Department of Radiation Oncology, Freiburg, Germany; 9University of Würzburg, Department of Radiation Oncology, Würzburg, Germany; 10University of Würzburg, Department of General and Visceral Surgery, Würzburg, Germany; 11University of Frankfurt, Department of General and Visceral Surgery, Frankfurt, Germany; 12University Medical Center Göttingen, Department of Medical Statistics, Göttingen, Germany; 13University Hospital Mannheim, Department of Medical Oncology, Mannheim, Germany; 14University Medical Center Göttingen, Department of General and Visceral Surgery, Göttingen, Germany; 15University of Frankfurt, Department of Radiotherapy and Oncology , Frankfurt, Germany

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Purpose or Objective

In this multicenter, randomized, phase 2 total neoadjuvant therapy (TNT) trial, the sequence chemoradiotherapy (CRT) followed by consolidation chemotherapy (CT) and total mesorectal excision (TME) resulted in a higher pathologic complete response rate (pCR, primary endpoint) than CT followed by CRT in patients with stage II/III rectal cancer. Here, we report long-term results. 

Material and Methods

Patients were randomly assigned to group A for 3 cycles of fluorouracil, leucovorin, oxaliplatin prior to fluorouracil/oxaliplatin CRT (50.4 Gy), or to group B for CRT prior to CT. Secondary endpoints included oncological outcomes, chronic toxicity, patient reported outcome measures (PROM) for global health status (GHS)/quality of life (QoL), and Wexner stool incontinence score. 

Results

Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). After a median follow-up of 43 months, the 3-year disease-free survival (DFS) was 73% in both groups (HR, 0.95, 95% CI, 0.63-1.45, P = .82); the 3-year cumulative incidence of locoregional recurrence (6% v 5%, P = .67) and distant metastases (18% v 16%, P = .52) were not significantly different. Chronic toxicity grade 3-4 occurred in 11.8% and 9.9% in group A and B, respectively, at 3 years. The GHS/QoL score decreased after TME, but returned to pretreatment levels 1 year post-randomization with no difference between groups. Stool incontinence deteriorated 1 year post-randomization in both groups, and only improved slightly at 3 years, but never reached baseline levels. 

Conclusion

Both groups resulted in comparable oncological outcomes. CRT followed by CT should be the preferred TNT sequence if organ preservation is a priority. This sequence resulted in higher pCR without compromising DFS, toxicity or QoL. The TNT regimen as tested in group B of the CAO/ARO/AIO-12 has, upon adaptation, been selected for comparison against TNT according to the RAPIDO protocol in the ongoing ACO/ARO/AIO-18.1 trial (NCT04246684) of our group that uses 3-year organ preservation rate as primary endpoint.

ClinicalTrials.gov: NCT02363374; On behalf of the German Rectal Cancer Study Group