LBA26 - Neoadjuvant chemotherapy with CAPOX versus chemoradiation for locally advanced rectal cancer with uninvolved mesorectal fascia (CONVERT): Final results of a phase III trial

Background

Neoadjuvant chemoradiotherapy (nCRT) is a crucial component in the treatment of locally advanced rectal cancer (LARC). However, indiscriminate pelvic radiation in all LARC lacks clear long-term survival benefits while accentuating surgical complications and toxicity. Comparatively, neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment for LARC with uninvolved mesorectal fascia (MRF). This trial aimed to assess the the noninferiority of nCT with CAPOX versus nCRT with capecitabine in LARC with uninvolved MRF.

Methods

Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT arm) or CRT with capecitabine (nCRT arm). The primary end point is 3-year local-regional recurrence-free survival (LRRFS), defined as time interval between the date of randomization and any local or regional progression/relapse. NI of nCT could be established if the upper limit of the 2-sided 95% confidence interval (CI) of the LRRFS hazard ratio (HR) did not exceed 1.6 (NI margin). Secondary endpoints, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and long-term toxicity, were also reported.

Results

A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n=300; nCRT, n=289). LRFFA was analyzed after a median follow-up of 48 months. 3-year LRRFS was 97.4 % (95% CI, 95.5 to 99.3) in the nCRT arm and 96.3% (95% CI, 94.0 to 98.6) in the nCT arm, resulting in a HR of 1.08 (95% CI, 0.46 to 2.54). Table: LBA26

Conclusions

The noninferiority of nCT was not confirmed, primarily owing to the remarkably low incidence of local recurrence observed in both arms. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.

Clinical trial identification

NCT02288195.

Editorial acknowledgement

We thank Prof. Scott R Steele and Prof. Ji-Bin Li for providing the necessary writing assistance and editorial support during the development of the abstract.

Legal entity responsible for the study

The authors.

Funding

Sun Yat-sen University Clinical Research 5010 Program (grant number 2014013).

Disclosure

P. Ding: Financial Interests, Institutional, Royalties: Roche, MSD, Sanofi, Medtronic, Johnson & Johnson; Financial Interests, Institutional, Advisory Role: BGI Genomics. All other authors have declared no conflicts of interest.