Advancing Care in Colorectal Cancer: Navigating Treatment After Progression

Panelists discuss how third-line metastatic colorectal cancer treatment has evolved from limited options like FOLFOX and FOLFIRI to multiple available agents, including regorafenib, trifluridine/tipiracil, trifluridine/tipiracil plus bevacizumab, and fruquintinib, emphasizing the importance of comprehensive biomarker testing to identify rare fusions and actionable targets before selecting among these therapies, each with distinct mechanisms of action and tolerability profiles that require careful sequencing and adherence management to optimize clinical outcomes.

Panelists discuss how the SUNLIGHT trial's demonstration that adding bevacizumab to trifluridine/tipiracil improves overall survival and progression-free survival represents the best available data in refractory colorectal cancer, with quality of life findings showing longer time to definitive deterioration being particularly significant for patient counseling since patients in third-line and beyond settings prioritize both survival benefit and maintaining good quality of life, making this combination compelling as it provides efficacy improvement without dramatically compromising patient well-being.

Panelists discuss how managing common toxicities in combination therapies requires specific strategies including dose reductions and growth factor support for neutropenia with trifluridine/tipiracil, antihypertensive management for blood pressure elevations across different agents, and careful patient selection considering contraindications such as previous pelvic radiation (GI perforation risk), cardiac conditions, anticoagulation therapy (hemorrhage risk), hepatic impairment, advanced age, and complex pill burden management, emphasizing the importance of multidisciplinary care and selecting conscientious patients capable of adhering to precise dosing requirements.

Panelists discuss how real-world dose adjustment decisions in metastatic colorectal cancer are primarily driven by individual patient factors rather than package insert recommendations, emphasizing the importance of understanding each patient's goals, values, comorbidities, and tolerance thresholds through collaborative multidisciplinary decision-making, since patients frequently ask "how will this make me feel?" and often prioritize quality of life over strict adherence to standard dosing, with the key insight that dose reductions can maximize efficacy by keeping patients on therapy longer rather than causing treatment discontinuation from intolerable toxicities.

Panelists discuss how common barriers to implementing trifluridine/tipiracil plus bevacizumab combination therapy include complex pill burden management with multiple bottle strengths that can confuse patients during dose reductions, procedural complications requiring bevacizumab holds that patients sometimes fail to disclose in advance, and hypertension management challenges that create patient anxiety about treatment delays, while emphasizing that adherence support strategies include close monitoring with biweekly visits, written dosing calendars, alternative five-day dosing schedules aligned with infusion timing, and incorporating patient-reported outcomes into shared decision-making to optimize treatment success despite these practical barriers.

Panelists discuss how multidisciplinary care for refractory metastatic colorectal cancer involves collaborative decision-making through tumor boards, specialized oral oncology pharmacists for financial assistance and patient support, transitions of care teams, and independent pharmacist-patient conversations that often reveal concerns patients won't share with prescribers, while emphasizing that balancing survival extension with quality of life requires understanding individual patient desires and life goals, incorporating patient values into treatment decisions by assessing their tolerance for side effects and supportive care burden, and recognizing that what's clinically meaningful to providers may differ significantly from what matters most to each individual patient.

Panelists discuss how the SUNLIGHT trial's success stems from its methodical design with robust single-arm and randomized phase two data that earned NCCN guideline inclusion before the phase three study, comprehensive quality of life data collection, and straightforward methodology, while acknowledging that the absence of consensus definitions for clinically meaningful outcomes in refractory metastatic colorectal cancer forces providers to rely on individual thresholds when evaluating hazard ratios, confidence intervals, and safety profiles, with the additional challenge that different organizational frameworks (ASCO, ESMO) use varying criteria for progression-free survival and overall survival endpoints, making consistent trial interpretation difficult without standardized consensus definitions.

Panelists discuss how endpoint prioritization in late-line metastatic colorectal cancer therapy differs between providers and patients, with pharmacists focusing primarily on progression-free survival and quality of life since patients frequently ask about living long enough to reach specific life events rather than overall survival statistics, while oncologists balance survival importance with comfort using regimens that have robust response rates and good quality of life even without level-one survival evidence, emphasizing that future research must be patient-centered by incorporating patient advocates and understanding what patients truly value most, as demonstrated by the disconnect between clinician focus on recurrence risk versus patient concerns about ostomy outcomes in rectal cancer, and requiring multidisciplinary approaches to staying current with evolving data through journal clubs, professional organization memberships, and increasingly social media platforms as starting points for identifying relevant clinical developments.

Panelists discuss how future research in refractory metastatic colorectal cancer must prioritize patient-centered approaches by incorporating patient advocates to understand what patients truly value and care about most, citing the example of rectal cancer where clinicians focus on recurrence risk while patients prioritize ostomy concerns, emphasizing that historically clinical trial design has not adequately asked patients about their priorities, and explaining that staying current with rapidly evolving data requires multidisciplinary strategies including journal clubs with board-certified oncology pharmacists, morning huddle meetings for clinical pearls, pharmacy resident presentations, professional organization memberships like ASCO for daily updates, and increasingly using social media platforms like Twitter as starting points to identify relevant clinical developments before delving deeper into primary literature.

Panelists discuss how the importance of having pharmacists embedded in oncology clinics has transformed metastatic colorectal cancer care by enabling real-time decision-making and dose adjustments, while highlighting that these are exciting times with multiple new oral treatment options that patients often prefer over infusions, though managing adherence and side effects remains challenging, and emphasizing that current targeted therapy opportunities include rare but actionable NTRK fusions, HER2 amplifications (3% of cases with multiple treatment options), and KRAS G12C mutations (3% of cases), with future promise in pan-RAS inhibitors, expanded immunotherapy beyond MSI-high tumors, and combination therapies, though dermatologic toxicity from targeted agents like RAS inhibitors will likely be the rate-limiting factor requiring better assessment tools and multidisciplinary management including dermatology support.