Patients with locally advanced rectal cancer are more likely to achieve a pathologic complete response (pCR) if they are given chemoradiotherapy before chemotherapy as part of preoperative total neoadjuvant therapy (TNT); conclude German investigators. The findings come from a randomized phase 2 “pick the winner” trial; known as CAO/ARO/AIO-12; that compared two TNT sequences based on oxaliplatin(Eloxatin, Sanofi Aventis) in more than 300 patients.
Given chemoradiotherapy before
The trial showed that giving chemoradiotherapy before chemotherapy led to significant improvements in pCR rates over those seen historically; at 25% vs 15%. Giving chemotherapy followed by chemoradiotherapy prior to surgery did not improve response rates. In addition; those patients who underwent chemoradiotherapy before surgery are more likely to experience grade 3/4 chemoradiotherapy-relate toxicity.
The sequence of TNT also affected compliance with therapy. Patients give chemotherapy first are less likely to receive all of their chemoradiotherapy, whereas those who receive chemoradiotherapy first are less likely to complete their subsequent chemotherapy. The results are present here at the World Conference on Gastrointestinal Cancer (WCGC) 2019 (abstract O-011) by lead investigator Ralf-Dieter Hofheinz, MD, Interdisciplinary Tumor Center, University Hospital Mannheim, Germany.
“This is the first randomized trial comparing both of these potential strategies of total neoadjuvant therapy;” he told the meeting. “It turns out that, in our study, chemoradiotherapy followed by consolidation chemotherapy reach the primary endpoint and is now the winner;” he said. He added that this approach has been chosen for an upcoming phase 3 trial (ACO/ARO/AIO-18.1) that is compare preoperative oxaliplatin-base its and consolidation chemotherapy with standard fluorouracil(5-FU)–based chemoradiotherapy in intermediate- and high-risk rectal cancer.
Commenting on the study, Eric van Cutsem, MD, PhD; from the University Hospital Gasthuisberg, Leuven, Belgium; who is cochair of the congress, said that “the field of locally advance rectal cancer is evolving, that is clear.” He told Medscape Medical News: “What we see is that there is a clear move towards total neoadjuvant treatment; including chemotherapy and chemoradiotherapy. We don’t know yet completely what is the best strategy.” van Cutsem says the current study “builds on the strategy of rectal cancer.”
Advanced rectal cancer
He underlined that although the trial did not move the field forward per se; it offered greater understanding of treatment sequencing and how that affects compliance. He personally believes that for advanced local tumors; probably not all patients are irradiate and that more patients are give combination chemotherapy.van Cutsem continue: “Probably the best is going to be that; to personalize that a bit more; maybe in the future give more chemotherapy and then, in some patients, after combination chemotherapy; irradiate them if the mesorectal fascia is still involve.”