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 

 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.

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Afsaneh Barzi, MD, PhD, discusses the frontline use of FOLFOXIRI plus bevacizumab and subsequent therapies in patients with metastatic colorectal cancer.

Afsaneh Barzi, MD, PhD, director, AccessHope™, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses unmet needs associated with the adjuvant treatment of patients with gastroesophageal cancers and highlights the use of nivolumab (Opdivo) in this setting.

Although there has been excitement following the implementation of new agents in the treatment of patients with metastatic gastroesophageal cancers in the scope of metastatic disease, there are currently no data confirming the benefit with immunotherapy agents in the adjuvant setting, Barzi begins. However, one exception to this unmet need is the data produced from the use of adjuvant nivolumab for patients who have had neoadjuvant chemoradiation or surgery with residual disease, and went on to receive nivolumab, Barzi explains. Treatment with adjuvant nivolumab in patients with resected esophageal or gastroesophageal junction cancer (GEJ) was evaluated in the phase 3 Checkmate 577 trial (NCT02743494), and led to the 2021 

Outside of this randomized, multicenter, double blind study of nivolumab, other completed trials have not met their primary end point with perioperative therapy or adjuvant therapy for gastric cancer, Barzi expands. Therefore, investigators cannot extrapolate these data and use these agents with curative intent outside of the patient populationin Checkmate 577, Barzi emphasizes, noting that this is important for oncologists to keep in mind when treating patients.

Although HER2-directed therapy has been an effective option for patients with metastatic disease fall into the metastatic setting, the trials that have been conducted in the early-stage setting have led to negative results thus far, Barzi says. Therefore, Based on this research and the outcomes that followed, these agents should be limited to use in the metastatic setting at this time, Barzi concludes.

Afsaneh Barzi, MD, PhD, discusses unmet needs associated with the adjuvant treatment of patients with gastroesophageal cancers and highlights the use of nivolumab in this setting.


Dr Barzi on Unmet Needs in the Adjuvant Treatment of Gastroesophageal Cancers

Afsaneh Barzi, MD, PhD, director, AccessHope™, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses challenges treating oncologists face when aiming to navigate the treatment landscape of patients with gastroesophageal cancers and highlights the evolution of treatments for patients with these diseases.

Oncologists face challenges in multiple areas when treating patients in this arena, Barzi begins. In years past, all esophageal gastric cancers were combined with one another when studied in clinical trials and treated in clinical practice, she explains. In current and future clinical trials investigating chemotherapy in patients with gastroesophageal cancers, the tumor histology, location, and presentation as either esophageal or gastric should all be considered, especially in the metastatic setting. Despite the importance of differentiating between tumor characteristics in these diseases, earlier clinical trials included all types of gastroesophageal cancers, Barzi says.

However, in the modern era of treating patients with these diseases, the development of targeted therapies has now led to the differentiation of these treatments by tumor histology, she expands. Now, oncologists can stratifypatients by tumor type. For example, investigators can differentiate a patient with squamous cell carcinoma from one with adenocarcinoma and further differentiate patients based on the locations of their tumors, such as esophageal vs gastroespohageal, Barzi emphasizes. Notably, some tumors are located higher up in the esophagus, whereas others are located closer to the stomach, Barzi adds.

Overall, the gastroesophageal cancers treatment paradigm is moving away from considering all these diseases as one, Barzi says. Instead, researchers are now separating them into different entities for the application of investigational data, which will in turn benefit patient outcomes, Barzi continues. Looking to the future, Barzibelieves that oncologists will stop combining certain subtypes of gastroesophageal cancer and will instead continue to determine the optimal therapies for each patient based on their individual disease characteristics.

Afsaneh Barzi, MD, PhD, discusses challenges treating oncologists face when aiming to navigate the treatment landscape of patients with gastroesophageal cancers and highlights the evolution of treatments for patients with these diseases.


Afsaneh Barzi, MD, PhD

Articles

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

Dr Barzi on Unmet Needs in the Adjuvant Treatment of Gastroesophageal Cancers

Dr Barzi on the Evolution of Treating Gastroesophageal Cancers