A. David McCollum, MD, attending oncologist, Baylor University Medical Center, discusses the clinical utility of regorafenib (Stivarga) in metastatic colorectal cancer (mCRC).

Trifluridine/tipiracil (Lonsurf) and regorafenib both have indications for the treatment of mCRC. Though they have never been compared head-to-head, they have each been compared with supportive care which is the standard in patients with refractory disease. Both offer an advantage for patients if used earlier enough in a patient’s course of treatment, says McCollum.

With regorafenib, there was some concern with dosing and excess toxicity. However, the ReDOS trial looked at a different dosing strategy. It started at a lower dose as opposed to the standard dose of 160 mg daily. The study started patients at 80 mg and, each week patients were on therapy, the dose was escalated to individual patient’s tolerance. The study convinced most physicians that a dose-escalation strategy showed better tolerance, explains McCollum, as more patients were able to stay on the drug for a longer period of time.

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Dr. McCollum on the Clinical Utility of Regorafenib in mCRC

A. David McCollum, MD, oncologist, Baylor University Medical Center, discusses maintenance therapy for patients with metastatic colorectal cancer (mCRC).

McCollum says that there are 4 studies that have helped to establish the role of maintenance therapy in mCRC—OPTIMOX1 and 2, CAIRO3, and PROT-AGE. The PROT-AGE study showed that single-agent bevacizumab (Avastin) in the maintenance setting does not provide much benefit over a chemotherapy-free interval. Still, these studies have shown that some form of maintenance is probably better than a chemotherapy-free interval. There are select patients for whom a chemotherapy-free interval might be appropriate, McCollum notes.

The best strategy in the treatment of patients with mCRC, he explains, is likely deintensifying to some form of maintenance therapy. It is still up for debate whether fluoropyridine, fluoropyridine plus an antibody, or an EGFR-directed antibody alone is the best option. McCollum says that the concept of transitioning from induction to a maintenance-type of treatment is important, and the message of that should be spread.

A. David McCollum, MD, oncologist, Baylor University Medical Center, discusses maintenance therapy for patients with metastatic colorectal cancer.
 

Dr. McCollum on Maintenance Therapy for Metastatic CRC

A. David McCollum, MD, oncologist, Baylor University Medical Center, discusses molecular testing in patients with colorectal cancer (CRC).

Physicians at large tertiary or quaternary referral centers may think that molecular testing is commonly done in patients with CRC, but McCollum states that this is not always the case. Population-based studies reveal that molecular testing is done far less than is commonly believed. McCollum recalls a case he consulted on in which the basic pathology report had no evidence of molecular testing.

profiling is an important test for physicians to consider, as well as 

 tests that look at both the common and less common sites of mutation. While there are the 

 V600E mutations, there are some non-V600E mutations that, although less common, are probably important to know about, says McCollum. Increasingly in the era of checkpoint inhibitors, physicians want to know about the microsatellite instability status and the mismatch repair gene expression. Those are the foundational molecular features physicians need to know, states McCollum.

Dr. McCollum on Molecular Testing in CRC

A. David McCollum, MD, oncologist, Baylor University Medical Center, discusses frontline therapy for patients with metastatic colorectal cancer (mCRC).

There are many frontline therapies for patients with mCRC. A lot of the decision comes down to sidedness and toxicity, explains McCollum. Whether the primary tumor originates in the right side of the colon or the left side of the colon will direct a physician’s choice of therapy. Data has consistently shown that patients who have right sided tumors typically do not do well with an EGFR antibody-containing regimen. Sidedness and the molecular profile of the tumor are the biggest determinants between an EGFR antibody and a VEGF antibody, explains McCollum.

Deciding which chemotherapy to combine that with comes down to patient preferences, toxicity, and provider comfort level, says McCollum. A patient who does better on a regimen that spares neuropathy will typically receive an irinotecan-containing regimen such as FOLFIRI. If a patient has experienced more gastrointestinal toxicity from the start of treatment and wants to avoid the risk of diarrhea and enteritis, a physician may opt for an oxaliplatin-based therapy, says McCollum.

Dr. McCollum on Frontline Therapy for Patients With Metastatic CRC

A. David McCollum, MD, Baylor-Sammons Cancer Center, discusses integrating immunotherapy into the treatment landscape of colorectal cancer (CRC).

According to McCollum, patients who have microsatellite instability-high (MSI-H) phenotype or a mismatch-repair deficient immunohistochemistry profile seem to be the patients who derive the most benefit from PD-1/PD-L1 inhibitors. There are subsets of patients who are outside of that subgroup who also derive some benefit, but patients with MSI-H tumors clearly have the most benefit.

There is an ongoing trial investigating chemotherapy versus a PD-1 inhibitor. It is accruing slowly, as it is only a small subset of patients, but there is already a lot of belief in the community that this group needs to receive a checkpoint inhibitor, explains McCollum.

Dr. McCollum Discusses Immunotherapy in CRC

A. David McCollum, MD, Baylor-Sammons Cancer Center, discusses drug sequences for patients with colorectal cancer (CRC).

Patients with CRC are generally treated with a biologic drug in combination with chemotherapy. Over time, the intensity of the chemotherapy is modified or lightened to try to maintain benefit for as long as possible.

There is still debate about which maintenance therapy is best for frontline treatment, as well as what constitutes as enough progression for a patient to need second-line therapy, says McCollum.

Dr. McCollum on Drug Sequences for Patients With CRC

A. David McCollum, MD, physician, Texas Oncology, discusses treatment options in the first-line setting for patients with colorectal cancer (CRC).

According to McCollum, there was a burst of activity in the early part of this millennia with the approval of many agents. It was discovered that there were some molecular predictors to optimize regimens for particular forms of CRC.

 testing might specify certain regimens for patients. Additionally, the sidedness of the tumor may predict which treatment will be successful, explains McCollum.

A. David McCollum, MD

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