Abstract
Therapeutic options for chemorefractory metastatic colorectal cancer (mcrc) have significantly expanded since 2009. The oral targeted therapies regorafenib and trifluridine/tipiracil have been established to be efficacious and safe in patients with mcrc who have progressed beyond 2 or more lines of chemotherapy. Evidence for the use of immunotherapy in a subgroup of this patient population is also encouraging, particularly in patients with mcrc that exhibits high microsatellite instability or deficient mismatch repair. Those significant advances have led to Health Canada approval of 3 novel therapeutic options for the treatment of patients with chemorefractory mcrc. However, the limited clinical efficacy of those treatments underscores the need for ongoing development of systemic therapy options for this unique cohort of patients. Here, we review the current and emerging treatment landscape for chemorefractory mcrc.
Highlights
Colorectal cancer is the 2nd most common cancer in the Canadian population, with more than 25,000 patients diagnosed in 20171
Since the start of the 2000s, primary systemic therapy for unresectable mcrc has consisted of fluorouracil-based chemotherapy in combination with oxaliplatin or irinotecan, which has an associated overall survival of up to 24 months[8,9]
The international, double-blind, placebo-controlled recourse trial evaluated the use of trifluridine/tipiracil in patients who had experienced progression while taking fluorouracil, oxaliplatin, irinotecan, bevacizumab, and egfr-targeted therapy[16]
Summary
Colorectal cancer (crc) is the 2nd most common cancer in the Canadian population, with more than 25,000 patients diagnosed in 20171. The addition of biologic therapy targeting either vascular endothelial growth factor (vegf) or the epidermal growth factor receptor (egfr—in RAS wild-type disease) to combination chemotherapy has further improved patient outcomes, with median os improvements reaching upwards of 30 months[10,11,12]. Despite those notable improvements in first- and second-line systemic therapies, many patients will develop progressive disease on those standard chemotherapy regimens, establishing the need for systemic therapy options in the chemorefractory setting (Figure 1)
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