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Managing mCRC

CE / CME

Opportunities and Challenges in Management of Metastatic Colorectal Cancer

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners: 1.00 Nursing contact hours, includes 1.00 hour of pharmacotherapy credit

Released: May 02, 2023

Expiration: May 01, 2024

Robert Lentz
Robert Lentz, MD
CME/CE Information

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First-line Treatment of mCRC

The first major branch point when selecting initial therapy is whether or not a patient is able to tolerate intensive therapy and can benefit from a high tumor response rate. For the majority of patients able to tolerate intensive therapy, standard chemotherapy (FOLFOX, FOLFIRI, CAPEOX) regimens with or without a biologic agent (EGFR inhibitor or bevacizumab) are recommended. These regimens are based on intravenous 5-fluorouracil or oral capecitabine plus oxaliplatin or irinotecan. Table 1 outlines a recommended approach to patients based on disease and patient characteristics, as recommended by ASCO and NCCN for patients with mCRC who have not previously received treatment in the metastatic setting.4,5,12

Table 1. Preferred Initial Therapy of mCRC: Patients Appropriate for Intensive Therapy4,5,12 

The PARADIGM trial, which compared chemotherapy plus panitumumab (EGFR inhibitor) or bevacizumab for patients with left-sided, MSS, wild-type RAS mCRC, demonstrated the superiority of EGFR inhibition vs bevacizumab, with response rates up to 80% and improved survival.14 Other clinical trial data have shown that patients with left-sided tumors have better outcomes when treated with chemotherapy plus an EGFR inhibitor vs chemotherapy plus bevacizumab.11,14,15 Thus, chemotherapy plus cetuximab or panitumumab is preferred for patients with left-sided, MSS disease and wild-type RAS/BRAF.4,5,12 However, depending on their goals of care, some patients may prefer bevacizumab rather than an EGFR inhibitor if they wish to avoid the rash associated with the EGFR inhibitors.

Although doublet chemotherapy is recommended for the majority of patients, triplet chemotherapy regimens may be appropriate for some younger, fitter patients.4,5,12 In the United States, the triplet regimen FOLFIRINOX (rather than FOLFOXIRI) is recommended because of its lower dose of 5-fluorouracil, which seems to be better tolerated in patients with folate-fortified diets.

For patients who require less intensive therapy, single-agent chemotherapy with or without an EGFR inhibitor or bevacizumab is appropriate; another option is single-agent EGFR inhibitor. More frail patients with HER2-positive disease may benefit from trastuzumab plus pertuzumab, tucatinib, or lapatinib while avoiding chemotherapy toxicity.4,5,12

 

 

The KEYNOTE-177 trial demonstrated which of the following with first-line pembrolizumab vs chemotherapy for MSI-high/dMMR mCRC?

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