Adding Oxaliplatin to Capecitabine-Based Chemotherapy, Radiation May Not Improve Survival in Rectal Cancer

CHICAGO —The addition of oxaliplatin to both neoadjuvant capecitabine plus radiotherapy and adjuvant capecitabine does not improve survival outcomes among patients with locally advanced rectal cancer, according to an oral presentation at the 2018 American Society of Clinical Oncology Annual Meeting.¹

Although a relatively small portion of patients (5%-6%) undergo locoregional relapse after preoperative chemoradiation and adjuvant 5-FU, long-term survival remains only about 65%; further improvements are needed.

In the phase 3 PETACC-6 study (ClinicalTrials.gov Identifier: NCT00766155), researchers randomly assigned 1090 patients with advanced rectal adenocarcinoma to 5 weeks of preoperative capecitabine-based chemoradiation with or without oxaliplatin followed by 6 cycles of capecitabine alone (Cape) or with oxaliplatin (CapeOx) (before and after surgery). Eligible patients had no evidence of metastatic disease and had resectable disease or were expected to become resectable.

A previous analysis at median follow-up of 31 months demonstrated no significant difference in disease-free survival (DFS) between the study arms (adjusted hazard ratio [HR], 1.04; 95% CI, 0.81-1.33; P = .781).

After a median follow-up of 68 months, there were 157 DFS events and 97 deaths among patients in the capecitabine arm, and 156 DFS events and 109 deaths among patients in the oxaliplatin arm; there was no difference in DFS between the two groups or in overall survival (OS).

The 5-year DFS rate was 71.3% (95% CI, 67.1-75.0) among patients treated with capecitabine alone compared with 70.5% (95% CI, 66.3-74.3) among patients in the oxaliplatin arm (HR, 1.02; 95% CI, 0.82-1.28; P = .835). Extended analysis showed that the 7-year DFS was 66.1% versus 65.5% among patients in the Cape and CapeOX arms, respectively.

The 5-year OS rate was 83.1% (95% CI, 79.5-86.1) among patients in the Cape arm versus 80.1% (95% CI, 76.2-83.4) among patients in the CapeOx (HR, 1.17; 95% CI, 0.89-1.54; P = .252). Seven-year OS was 73.5% versus 73.7% % among patients in the Cape and CapeOX arms, respectively.

Relapse-free survival (RFS) was reported as 77.3% and 78.1% among patients in the Cape and CapeOx arms, respectively (HR, 0.99; 95% CI, 0.73-1.32; P = .94).

Interestingly, no baseline characteristics were observed to affect DFS except for being of German descent; German patients had poorer DFS outcomes with oxaliplatin (HR, 1.27; 95% CI, 0.96-1.68; P = .091) while non-German patients had improved DFS outcomes (HR, 0.65; 95% CI, 0.44-0.97; P = .033).

The authors concluded that “with this final analysis after a median follow-up of 5.7 years, there is no benefit by the addition of oxaliplatin to chemo-radiotherapy and adjuvant chemotherapy.”

Read more of Cancer Therapy Advisor‘s coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

1. Schmoll HJ, Haustermans K, Price TJ, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine +/- oxaliplatin in locally advanced rectal cancer: Final results of PETACC-6. Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.