Ryan Haumschild, PharmD, MS, MBA, leads a discussion on managing toxicities and assessing treatment failure in metastatic colorectal cancer (mCRC) with insights from John L. Marshall, MD; Ben George, MD; and David Fenstermacher, PhD.

Dr Haumschild highlights the importance of synergistic treatment plans that combine traditional agents with targeted mutations. He acknowledges the interest in leveraging different mechanisms of action but mentions that this approach can introduce various toxicities, such as nausea, vomiting, or myelosuppression. He turns to Dr Marshall for pearls on managing these toxicities, especially for first- and second-line agents.

Dr Marshall stresses that toxicity often depends on the administration rather than the drugs themselves and points out that colon cancer does not exhibit a typical dose-response curve. He advocates for judicious drug use, noting that full doses are not always necessary. He highlights the challenge of managing adverse effects of new medicines and the importance of understanding these innovations more fully.

Dr Fenstermacher mentions clinical trials that have demonstrated the efficacy of lower doses, emphasizing safety considerations in dosing decisions.

The discussion touches on the significance of pharmacogenomics in dosing, emphasizing dosing tailored to individual patients and the importance of setting clear expectations for patients regarding potential dose reductions.

The conversation then shifts to assessing treatment failure. Dr George emphasizes that defining treatment failure depends on the initial treatment goal set with the patient. He highlights the importance of upfront comprehensive genomic profiling to identify potential targeted therapies and setting short-term goals to adapt to the evolving cancer response.

The panel encourages open discussions between clinicians and patients to set personalized goals. Dr Marshall introduces the chessboard analogy, emphasizing that the choice of the right treatment strategy is a dynamic process that should align with patient goals, performance status, and response.

The discussion transitions to third-line therapies, such as regorafenib and trifluridine-tipiracil, with Dr Marshall emphasizing the importance of using these therapies strategically. He compares them to chess pieces and encourages utilizing them at the right time in a patient’s journey, emphasizing that they can serve as bridges to the next therapy.

The conversation underscores the need for adaptable and personalized treatment approaches, considering patient goals, quality of life, and long-term strategies, all guided by the analogy of a chessboard where the right piece should be moved at the right time.

Video synopsis is AI-generated and reviewed by AJMC editorial staff.