Third-line and Later-line Therapies in R/R mCRC



Axel Grothey, MD: When we switch patients from line to line of therapy, the main driver is progression of disease. Sometimes there are toxicity issues when patients, for instance, have a neurotoxicity on oxaliplatin-based therapy. But even then, we would probably go to a maintenance therapy setting and then try to see whether the neurotoxicity fades or gets better over time. The driver is really switching treatment based on progression of disease and, to a lesser degree, patient intolerance. Fortunately, we have third-line treatment options available, so patients actually have opportunities to continue on treatment.

Marwan Fakih, MD: How important is it for our patients to maintain physical fitness in the setting of colorectal cancer? There is strong evidence that patients who have stage II and stage III disease, for example—who have undergone a curative resection and have been engaged in a high level of physical activity—fare better than patients who are sedentary. There is a suggestion that those patients who maintain a high level of physical activity have a lesser chance of relapse.

Those data have been published and shown to be the case for earlier-stage disease. How much these data apply for stage IV disease at this point is not very clear. However, we know very well that our ability to give chemotherapy, our ability to stay with systemic treatment or even targeted therapies, is dependent on our physical condition and also our ability to tolerate the chemotherapy per se, which is impacted by our physical activity. Chemotherapy causes fatigue, and fatigue causes deconditioning. It becomes a vicious cycle sometimes in our patients. We always encourage our patients to actually push themselves further. We encourage them not to stay at home. We encourage them to be involved in exercise and physical activity, to take long walks. I do think that’s helpful for our patients, not only physically but mentally. So yes, we do encourage our patients to maintain a very high level of physical activity and an active lifestyle.

Scott Kopetz, MD, PhD: In later lines, the FDA-approved therapies are regorafenib and TAS-102 [trifluridine, tipiracil]. These are oral options given as single agents for our patients. There are data also about how TAS-102 may be combined with bevacizumab in a number of studies, including some that are randomized with potential benefit and certainly other areas of active research and investigation. It’s fair to say that in clinical practice there are also opportunities for oxaliplatin rechallenge in later lines, as well as rechallenge with EGFR inhibition for those patients who had a good benefit and where there has been some period of time since their prior EGFR exposure.

Transcript Edited for Clarity

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