565P - Neoadjuvant chemotherapy, excision, and observation for early rectal cancer: The phase II NEO trial (CCTG CO.28) results after minimum 3 years follow up

Background

In early-stage rectal cancer, short term results of neoadjuvant chemotherapy combined with transanal endoscopic surgery (TES) demonstrate promise as a strategy for organ preservation with acceptable early oncologic and functional outcomes. The objective of this study was to analyse medium term oncologic and functional outcomes of the NEO trial patient cohort.

Methods

This multicenter, phase II trial included patients with clinical T1-T3abN0M0 low- or mid-rectal adenocarcinoma eligible for TES who were treated with 3 months of chemotherapy (mFOLFOX6 or CAPOX). Patients with endoscopic and MRI evidence of tumor response proceeded to TES within 6 weeks of treatment completion. All patients followed an intensive surveillance regimen for a minimum of 3 years postop, including endoscopy, MRI, CT scan and quality of life/ low anterior resection syndrome (LARS) questionnaires.

Results

Between August 2017 and May 2020, 58 patients were recruited at 7 North American centers. Of these, 71% (41/58) were male and median age was 66 (range 31-83) years. All patients commenced chemotherapy and 56 proceeded to TES. Of these, 33/58 (57%) patients had tumor downstaging to ypT0/1 and were recommended protocol-specified surveillance for organ preservation. While 10/23 patients with persistent yT2 agreed to total mesorectal excision (TME), 13 patients declined, resulting in 46/58 (79%) organ preservation. At median follow up 4.3 years (range 3.3 – 5.6 years), 4 patients experienced local recurrence: 3 endoluminal and 1 nodal. Overall, 3-year locoregional relapse free survival was 92.9% (95% CI 82.3-97.3%) and 3 year distant disease free survival was 94.7% (95%CI 84.6-98.3%). Overall disease free survival was 84.3% (95% CI 72.0-91.5[LJ[1] %). At 3 years post TES, major, minor, and no LARS was experienced in 22%, 19%, and 59%, respectively, in patients with successful organ preservation.

Conclusions

For patients with early rectal cancer, a novel strategy of three months of induction chemotherapy combined with TES achieved organ preservation with good oncologic and functional outcomes after 3 years of follow up in this phase II study.

Clinical trial identification

NCT03259035.

Editorial acknowledgement

Legal entity responsible for the study

Canadian Cancer Trials Group.

Funding

Canadian Cancer Trials Group (CCTG).

Disclosure

C.J. Brown: Financial Interests, Personal, Invited Speaker, Fellowship educational event: Ethicon; Financial Interests, Institutional, Funding, ebrs.online support: Medtronci. J.M. Loree: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Novartis, Ipsen, Bayer, Roche, Pfizer, Guardiant Health, Saga Diagnostics. R. Auer: Financial Interests, Personal, Speaker, Consultant, Advisor: Incyte; Financial Interests, Personal, Advisory Board: Takeda, Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Institutional, Research Funding: Qu Biologics, Miso-chip. D. Jonker: Financial Interests, Institutional, Research Funding: Amgen, Pfizer, Genentech, 23me, GSK, AstraZeneca, Seagen, Janssen, Ocellaris, Signalchem, Arcus Biologics, Gilead, Qu Biologics. M. Raval: Financial Interests, Institutional, Research Funding: Cook Medical. V. Simianu: Financial Interests, Personal, Advisory Board: BD Surgical; Financial Interests, Personal, Advisory Role: C-SATS Inc; Financial Interests, Personal, Funding: Intuitive Surgical Inc. L. Pitre: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Merck, AstraZeneca; Financial Interests, Institutional, Funding: Pfizer. K. Neumann: Financial Interests, Institutional, Research Funding: GSK. D. Bosse: Financial Interests, Personal, Speaker’s Bureau: Ipsen, EMD Serono, Janssen; Financial Interests, Personal, Stocks/Shares: NEED; Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer; Financial Interests, Personal, Speaker, Consultant, Advisor: Knight Pharmaceutical, Amgen, Merck, Abbvie, Pfizer, BMS, CUS. All other authors have declared no conflicts of interest.