ASCO 2025: Current Insights and Emerging Approaches in Managing Treatment-Resistant Metastatic Colorectal Cancer - Episode 10
Panelists discuss how they approach rechallenge with chemotherapy, considering it primarily in patients who never truly progressed on oxaliplatin-based therapy or those who might benefit from EGFR antibody reintroduction after a drug holiday.
The decision between rechallenge with previous chemotherapy regimens versus proceeding to novel targeted agents presents a complex clinical dilemma in colorectal cancer (CRC) management. Oncologists must balance the modest survival benefits of newer agents against potential effectiveness of retreating with previously used chemotherapies, particularly when patients may become too debilitated for subsequent treatments. This strategic decision-making is complicated by financial incentives favoring intravenous therapies and established practices supporting rechallenge approaches.
Clinical scenarios most appropriate for rechallenge include patients who discontinued oxaliplatin-based regimens for maintenance therapy without true progression, and those who received EGFR antibody holidays before reintroduction. The heterogeneous nature of rechallenge data makes interpretation difficult, as studies often include patients who stopped treatment for reasons other than progression. Real-world evidence suggests that carefully selected patients may benefit from rechallenge strategies, particularly when previous treatments were discontinued due to toxicity rather than resistance.
The panel acknowledges ongoing struggles with these treatment sequencing decisions, emphasizing the importance of individualized patient assessment. Factors influencing these decisions include prior response duration, reason for treatment discontinuation, current performance status, and patient preferences. As novel oral therapies become available, the treatment landscape continues to evolve, potentially reducing the relevance of traditional rechallenge approaches while offering new sequential treatment opportunities for patients with advanced colorectal cancer.