CAPOX Regimen Appears Noninferior to FOLFOX in Colorectal Cancer

Image of colorectal cancer cells: © Digital Photo- stock.adobe.com

The treatment landscape for patients with resected stage III colon cancer has undergone a significant change, following publication of an International Development and Education Award (IDEA) presentation abstract in the August 2023 Journal of the National Comprehensive Cancer Network.¹ Investigators observed an increasing trend in the use of 3-month adjuvant therapy with CAPOX (capecitabine/oxaliplatin) vs the standard of care, 6 months of adjuvant FOLFOX (fluorouracil /leucovorin/oxaliplatin) therapy. Prior to the IDEA presentation, 14% of patients given this new treatment approach grew to 48% following it (adjusted odds ratio [aOR], 1.28; 95% CI, 1.20-1.37; ^P < .001).

The study sought to establish noninferiority, which was reached if the upper limit of the 2-sided 95% CI of the HR did not pass 1.12. Within subgroups of interest, no differences were observed in the use of CAPOX or for cancer risk: low risk (aOR, 1.27; 95% CI, 1.17-1.37) and high risk (aOR, 1.31; 95% CI, 1.16-1.47). However, the subgroup analyses, through a risk-stratified method, showed noninferiority for treatment regimen and duration.

Although the primary outcome was not achieved (HR, 1.07; 95% CI, 1.00-1.15), the subgroup analysis has made an impact on adjuvant chemotherapy practices. In individuals with low-risk colon cancer (T1-3 and N1 disease), a 3-month regimen showed noninferiority vs a 6-month duration (HR, 1.01; 95% CI, 0.90-1.12), with 3-year disease-free survival (DFS) rates of 83.1% and 83.3%, respectively. However, patients with high-risk disease (T4 or N2 or both) showed better DFS with 6 months vs 3 months of FOLFOX (3-year DFS, 73.6% vs 76.0%, respectively; HR, 1.16; 95% CI, 1.06-1.26).

The 5-year overall survival (OS) rate showed improvement with 6 months of chemotherapy over 3 months (82.8% vs 82.4%). Noninferiority in OS for 3 months vs 6 months of chemotherapy was not confirmed across the entire population (HR, 1.02; 95% CI, 0.95-1.11; noninferiority P =.058) or within subgroups.

The IDEA’s collaboration analysis included 6 multicenter, randomized phase 3 trials spanning 12 countries (NCT01150045, NCT00749450, and NCT01308086) examining 3-month vs 6-month courses of adjuvant chemotherapy of FOLFOX or CAPOX, measuring DFS.² The analysis encompassed a cohort of 399 patients who started their first chemotherapy dose between January 1, 2016, and January 31, 2021. Patients’ electronic health records were stratified according to presence of International Classification of Diseases Ninth Revision or Tenth Revision codes for colon cancers, diagnosis date on or after January 1, 2016, and documentation of oxaliplatin treatment within the health system. The records included patients diagnosed with stage III colon cancer who had undergone adjuvant chemotherapy using a CAPOX or FOLFOX.

When assessing the safety outcomes of the IDEA collaboration, investigators recognized lower rates of treatment-related adverse events (TRAEs), including diarrhea, neutropenia, and thrombocytopenia in patients undergoing 3 months of adjuvant chemotherapy vs 6 months. Grade 2 neurotoxicity was also significantly lower in individuals on the 3-month regimen (FOLFOX, 16.6% vs 47.7%, respectively; CAPOX, 14.2% vs 44.9%). Despite the failure to reach noninferiority with the 3-month adjuvant therapy across the entire population, the National Comprehensive Cancer Network guidelines for colon cancer now recommend 3 to 6 months for adjuvant chemotherapy based on risk classification.³

Although the IDEA collaboration did not achieve noninferiority across all patient groups, the findings showed a treatment change favoring the use of CAPOX with the shorter duration of treatment shown.

“Our next step is to present the actual clinical outcomes to see if the results of what we would see in typical practice are consistent with what was observed from the IDEA collaboration, understanding the caveats, and the limitation. It was not necessarily applicable to all patients and also did not include many Western patients receiving CAPOX as a treatment option. We are interested to see what the results of the clinical outcomes show and if it is consistent with what was observed from the IDEA collaboration. We plan to present and publish it hopefully in the near future” Daniel H. Ahn, DO, an oncologist, associate professor, and medical director of the Clinical Research Office at Mayo Clinic in Phoenix, Arizona, said in an interview with Targeted Therapies in Oncology.

REFERENCES:

1. Ou FS, Walden DJ, Larson JJ, et al. Changes in prescribing patterns in stage III colon cancer. J Natl Compr Canc Netw. 2023;21(8):841-850.e4. doi:10.6004/jnccn.2023.7028

2. Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378(13):1177-1188. doi:10.1056/NEJMoa1713709

3. NCCN. Clinical Practice Guidelines in Oncology. Color cancer, version 2.2023. Accessed May 25, 2023. https:// www.nccn.org/login?ReturnURL=https://www.nccn.org/ professionals/physician_gls/pdf/colon.pdf