Thorvardur (Thor) Halfdanarson, MD, an associate professor of medicine, Division of Medical Oncology; a medical oncologist; and an assistant program director for the Hematology/Oncology fellowship program at Mayo Clinic, discusses the evolving role of immunotherapy in colorectal cancer (CRC). 

Currently, immunotherapy is a standard of care for patients with mismatch repair deficient metastatic CRC in any line of treatment, Halfdanarson says. 

For example, pembrolizumab (Keytruda) and other checkpoint inhibitors have demonstrated significant efficacy in this patient subgroup.

Furthermore, patients now undergo genomic testing when they are diagnosed with early-stage and metastatic disease, says Halfdanarson.

Despite the interest that immunotherapy has garnered in the space, the utility of the modality is still unclear in patients with metastatic mismatch repair proficient or microsatellite stable tumors, Halfdanarson concludes. 

Videos

Thorvardur Halfdanarson, MD, discusses the evolving role of immunotherapy in colorectal cancer. 

Dr. Halfdanarson on the Evolving Role of Immunotherapy in CRC 

Thorvardur (Thor) Halfdanarson, MD, associate professor of medicine, Division of Medical Oncology; medical oncologist; assistant program director, Hematology/Oncology fellowship program, Mayo Clinic, discusses investigational agents that are being evaluated in patients with colorectal cancer (CRC) who do not harbor genomic alterations. 

For patients with CRC who do not harbor genomic alterations, systemic chemotherapy remains the standard of care, Halfdanarson says.

However, multiple novel agents that target the VEGF pathways are under investigation for use in this patient population, explains Halfdanarson.

Combination regimens such as bevacizumab (Avastin) plus TAS-102 (trifluridine/tipiracil; Lonsurf) are being considered. Additionally, the VEGF inhibitor fruquintinib is being tested in the United States after demonstrating promising efficacy and safety in the phase 3 FRESCO trial. Finally, regorafenib (Stivarga) is being evaluated in combination with immunotherapy, Halfdanarson concludes. 

Thorvardur (Thor) Halfdanarson, MD, discusses investigational agents that are being evaluated in patients with colorectal cancer who do not harbor genomic alterations.  



Dr. Halfdanarson on Investigational Agents in Driver-Negative CRC

Thorvardur (Thor) Halfdanarson, MD, associate professor of medicine, Division of Medical Oncology; medical oncologist; assistant program director, Hematology/Oncology fellowship program, Mayo Clinic, discusses the KEYNOTE-177 trial in microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). 

 evaluated pembrolizumab (Keytruda) in patients with MSI-H/dMMR mCRC, says Halfdanarson. Results from the trial were presented during the 

​Findings from the study demonstrated a doubling in progression-free survival with pembrolizumab compared with chemotherapy in this patient population.

FDA approved pembrolizumab as first-line therapy

 for patients with MSI-H/dMMR mCRC, according to results from the trial.

In recent years, the field has focused on the continuum of therapy, sparking interest in aggressive induction therapies followed by maintenance, ​as well as molecular targets, Halfdanarson concludes. 

Thorvardur (Thor) Halfdanarson, MD, discusses the KEYNOTE-177 trial in microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer.

Dr. Halfdanarson on the KEYNOTE-177 Trial in MSI-H/dMMR mCRC 

Thorvardur (Thor) Halfdanarson, MD, an associate professor of medicine, Division of Medical Oncology; a medical oncologist; and an assistant program director for the Hematology/Oncology fellowship program at Mayo Clinic, discusses the molecular differences between left- versus right-sided tumors in colorectal cancer (CRC).

In terms of tumor sidedness, it has been known for a long time that right-sided tumors are more likely to be 

 mutated, says Halfdanarson. Patients with 

-mutant tumors have a very poor prognosis compared with those who have 

 wild-type tumors. More recently, it has also been confirmed that not all 

-mutanttumors are created equal. Different mutations exist within CRC, one of the most common being 

 mutations, however, may be associated with prognosis in a different way; not all of them are associated with an inferior prognosis.

With the mismatch repair–deficient (dMMR) tumors, there is an interesting paradox, notes Halfdanarson. In general, right-sided tumors have a worse prognosis; this has been demonstrated in several trials. 

-mutant, right-sided tumors are also more likely to be dMMR, although that represents a relatively small proportion of all right-sided tumors. That small subgroup of patients with right-sided tumors responds well to immunotherapy, concludes Halfdanarson.

Thorvardur (Thor) Halfdanarson, MD, discusses the molecular differences between left- versus right-sided tumors in colorectal cancer.

Thorvardur Halfdanarson, MD

Articles

Dr. Halfdanarson on the Evolving Role of Immunotherapy in CRC

Dr. Halfdanarson on Investigational Agents in Driver-Negative CRC

Dr. Halfdanarson on the KEYNOTE-177 Trial in MSI-H/dMMR mCRC

Dr. Halfdanarson on Molecular Differences Between Left- Versus Right-Sided Tumors in CRC