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Axel Grothey, MD: In the last decade, we’ve seen major improvements in the outcome for patients with metastatic colorectal cancer that are mainly linked not necessarily to advances in first-line treatment but rather the availability of different lines of therapy, new treatment approaches, subsequent lines of therapy after progression of first-line treatment, and actually different interventions that can prolong the life of patients. We’re much more aggressive in liver resections—for instance, locoregional therapies. All this sums up in incremental steps to much longer overall survival over the last 10 years. It’s not just 1 effect that happened. We’ve never seen this imatinib in GIST [gastrointestinal stromal tumors]—like effect that 1 revolution or 1 drug really drove survival. We’ve seen the evolution of various different new treatment approaches, and that adds up to an overall survival improvement for patients.
Marwan Fakih, MD: How does the continuum of care in colorectal cancer improve the outcome of patients with colorectal cancer with metastatic disease? We have known for years now that it is very important to make available all strategies that are associated with improvement in survival, in response rate, in progression-free survival, and in the management of patients with metastatic colorectal cancer. Even prior to the era of targeted therapy when we had chemotherapeutic agents such as oxaliplatin, 5-FU [5-fluorouracil], and irinotecan, it was clearly shown that the ability to administer all active agents in the management of a patient with metastatic colorectal cancer contributes to the improvement in the overall survival of that patient.
The availability now of many targeted agents along with the presence of cytotoxic chemotherapy is essential in improving the outcome of patients with colorectal cancer. The ability to administer these agents sequentially or in combination has been associated with improvements in overall survival. Nowadays we look at the molecular profile of patients and identify which agents are associated with benefit in these particular patients in a precision medicine approach, along with the integration of cytotoxic chemotherapies in patients with metastatic colorectal cancers to get the optimal benefit and the optimal outcome in those patients.
Scott Kopetz, MD: When we think about how we’re utilizing chemotherapy agents in 2020 and beyond, we think about how we are sequencing together a number of different chemotherapies, as you heard, but also the opportunity to rechallenge and to use chemotherapy in different combinations. What we see is that the classic, clean perspective of lines of therapy rarely applies to most patients—that patients are undergoing treatment de-escalation, treatment intensification, rechallenges, and alternate approaches, and that the concept of lines don’t always apply.
This especially is the case in the number of patients who receive locoregional therapy, either surgery for oligometastatic disease, resection or radiation of primary tumor if needed, ablation, radiation of other sites as well. This is increasingly being incorporated into our treatment course. We’re recognizing that the lines of therapy are hard to define. Having said that, we see a number of patients who will be exposed to almost all the available treatments. For most patients, not all, we’re limited by the number of approved available therapies. It is not necessarily about the lines of therapy but is regarding if we have other active treatments that we can provide to them.
Transcript Edited for Clarity