Dr Dasari on Salvage Treatment Considerations for Unresectable Metastatic CRC

Arvind N. Dasari, MD, MS, associate professor, the Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses later-line therapies considerations in unresectable metastatic colorectal cancer (mCRC).

Resistance to standard treatments including cytotoxic agents like 5-fluorouracil (5-FU), irinotecan, oxaliplatin, and targeted therapies like anti-BRAF, anti-HER2, and anti-EGFR agents is common in patients with unresectable mCRC, Dasari begins. As such, identifying appropriate salvage therapies becomes critical upon progression, he states.

Prior to data from the phase 3 FRESCO-2 trial (NCT04322539), which in turn led to the FDA approval of Fruquintinib (Fruzaqla), patients few salvage therapy agents available in this treatment setting, including regorafenib (Stivarga) and trifluridine/tipiracil (TAS-102; Lonsurf), Dasari reports.

Dasari emphasizes that fruquintinib has expanded the landscape of later-line treatment options for refractory mCRC, offering an additional therapeutic avenue for patients who have exhausted previous lines of therapy. This represents a novel therapeutic approach for patients with mCRC who are truly refractory to all available therapies, he explains.

When deciding several factors must guide the selection of salvage therapy, including patient comorbidities, prior treatment history and associated toxicities, and disease burden, Dasari continues. For instance, liver health is a key factor since the liver is the most common site of metastasis in mCRC; the choice of therapy could be influenced by the patient's hepatic function and reserve. Patient preferences also play a crucial role, particularly when considering the route of administration, whether that be oral or intravenous, to minimize time in infusion centers.

Additionally, the cumulative adverse effects from previous treatments, such as oxaliplatin-induced neurotoxicity or hematologic toxicities from multiple therapies, may restrict subsequent therapeutic options.

Later-line treatment for unresectable mCRC requires an individualized approach that takes into account clinical parameters, patient preferences, and overall quality of life, Dasari concludes. The aim is to strike a balance between efficacy and tolerability, ensuring the chosen therapy aligns with the patient's clinical status and treatment goals.