Colorectal cancer is the third leading cause of cancer death among men and women in the United States. Each year, there are 149,500 new cases of colorectal cancer, and 52,980 people die from the disease. Treatment choice depends on many factors, including patient characteristics, tumor characteristics, molecular characteristics, and patient preferences. Approximately 21% of patients present with metastatic disease, which has a five-year survival rate of only 14%. Results from the CRYSTAL and PRIME studies, however, indicate promising treatment options for patients who have left-sided metastatic colorectal cancer. In this interview, Jaffer A. Ajani, MD, a medical oncologist at The University of Texas MD Anderson Cancer Center Department of Gastrointestinal (GI) Medical Oncology, discusses the challenges and progress in treating metastatic colorectal cancer.
What led you to pursue research on colorectal cancer? How has the field sustained your interest?
Jaffer A. Ajani, MD: In the beginning of my GI medical oncology career, I focused mainly on colorectal cancers. In the early part of my career, these were abundant patients. The incidence of these has remained high, although we have seen decline due to the early detection campaigns. The concern now is the rapidly increasing incidence of colorectal cancers in young individuals. Now I am focusing on the peritoneal spread of colorectal cancer and the immunotherapy resistance that is commonly noted in colorectal patients. This is a unique unmet need in GI cancers.
What are the most significant challenges that arise when treating patients with metastatic colorectal cancer?
Dr. Ajani: The good news is that the median survival of patients with metastatic colorectal cancer has increased substantially in the past 15 years. There are many reasons for this. There are more agents to treat patients with metastatic colorectal cancer: oxaliplatin, fluoropyrimidine, bevacizumab, cetuximab, panitumumab, BRAF inhibitors, trifluridine/tipiracil, regorafenib, and other antiangiogenic agents. Pembrolizumab or nivolumab/ipilimumab is used in microsatellite instability–high patients, and pembrolizumab is used in high tumor mutational burden patients. There are multidisciplinary approaches, which involve getting another opinion from your colleagues with diverse expertise. There is heightened sensitivity of microsatellite–unstable tumor patients, where immunotherapy can have a major effect. Unfortunately, young patients are coming down with these cancers. This is a big mystery to solve.
What are the most promising developments in treating metastatic colorectal cancer?
Dr. Ajani: Much greater understanding of molecular profiles/signatures/subtypes is needed. There are no other tools to do this. Multidisciplinary approaches have matured considerably. Several lines of therapies are available but still are not sufficient. We need even more effective treatments as most patients with advanced colorectal cancer die from it.
How do you think the treatment of metastatic colorectal cancer will evolve in the future?
Dr. Ajani: I believe that molecular and immune profiling, including enlarging liquid biopsy and next-generation sequencing platforms, will uncover smaller subsets of metastatic colorectal patients who will then benefit from customized approaches, and will also help to identify targets and allow better monitoring. The empiric approaches will reduce. Nevertheless, I can see that chemotherapy will be used for another 10 years—then its use will reduce.
What advice can you give to community oncologists treating patients with metastatic colorectal cancer?
Dr. Ajani: The most important piece of advice is to complete the recommended biomarker profile and act on it. Next is to engage surgeons and radiation oncologists at an appropriate moment to make a group decision. Finally, encourage patients to enroll in clinical trials and donate specimens for research.
About Dr. Ajani
Jaffer A. Ajani, MD, is a Professor of Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas and a medical oncologist with the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine. His research work topics include colorectal cancer and gastric cancer.
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Boeckx N, Koukakis R, Op de Beeck K, et al (2017). Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol, 28(8):1862-1868. DOI:10.1093/annonc/mdx119
Tejpar S, Stintzing S, Ciardiello F, et al (2017). Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol, 3(2):194-201. DOI:10.1001/jamaoncol.2016.3797
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.