Dr Barzi on the Real-World Use of Triplet Chemotherapies in mCRC

Afsaneh Barzi, MD, PhD, director, AccessHope™, associate professor, Department of Medical Oncology and Therapeutics Research, City of Hope, discusses the evaluation of the use of frontline FOLFOXIRI (fluorouracil [5-FU], leucovorin, oxaliplatin, and irinotecan) plus bevacizumab (Avastin) and subsequent therapies in the treatment of patients with metastatic colorectal cancer (mCRC).

CRC is a prevalent disease, with numerous patients diagnosed with metastatic disease annually in the United States and globally, Barzi begins. The standard treatment for patients with mCRC involves a combination of 2 chemotherapies, traditionally fluoropyrimidine plus oxaliplatin or irinotecan. However, in the past decade, the use of triplet chemotherapy, consisting of 5-FU plus oxaliplatin and irinotecan, has gained traction in the metastatic CRC patient population, she explains. The concept behind this triplet chemotherapy, which is more aggressive than doublet chemotherapy, is supported by data indicating a better response rate and tumor shrinkage with triplet vs doublet chemotherapy, Barzi notes. There is also evidence of progression-free survival improvement with triplet chemotherapy in the first-line setting, along with meta-analyses suggesting a potential association between triplet chemotherapy and improved overall survival, Barzi says.

Barzi goes on to elucidate that considering the rising incidence of CRC in younger adults, investigators wondered whether there was a differential in the use of this aggressive chemotherapy in younger vs older patients, and if so, what the trends in triplet chemotherapy utilization patterns and subsequent therapies in each age group were. To address these questions, investigators leveraged data from the Flatiron Health database to retrospectively examine the use of the triplet regimen from 2013 to 2023 in patients with mCRC, Barzi expands. The availability of biomarker information in this database is crucial. Despite the longstanding history of molecular testing for colorectal cancer, approximately 25% of patients in this dataset lacked documentation regarding KRAS mutational status, she says, which raises concerns about the timeliness of biomarker testing, indicating a potential suboptimal process.

Additionally, investigators observed that FOLFOXIRI was used less frequently than anticipated, especially in younger patients, despite confirmatory data with this regimen, Barzi continues. The single-digit percentages for the utilization of FOLFOXIRI in younger patients were unexpected, highlighting the need for better understanding of and education about this regimen in the patient populations it is indicated for use in, she concludes.