News >

Expert Discusses Finding the Optimal Treatment Strategy in CRC

Jason Harris
Published: Saturday, Aug 25, 2018

A. David McCollum, MD

A. David McCollum, MD

Treatment plans for patients with colorectal cancer (CRC), both in first-line and subsequent lines, are growing and changing, said A. David McCollum, MD. Selecting the optimal regimen, managing initial induction therapy and moving into maintenance therapy, means harnessing multiple individual data points and balancing efficacy with toxicity, he explained.

“There are some evolving strategies in the management of colon cancer. It's not as simple as one regimen and then there's not much else we can do,” said McCollum. “It's really a strategy of using the tools we have in our arsenal and trying to optimize the effectiveness and individualizing that to patients, not just through molecular features but also patient characteristics, such as sidedness.”

For previously treated patients with metastatic disease, McCollum said the dose-escalation regimen of regorafenib (Stivarga) explored in the phase II ReDOS trial and recommended by the National Comprehensive Cancer Network in March 2018 is likely to have widespread use. ReDOS showed that starting regorafenib (Stivarga) at a weekly dose of 80 mg and escalating to a weekly dose of 160 mg over 3 weeks induced less toxicity than the standard 160-mg dose, allowing patients to stay on treatment longer.

“That is going to become probably a more frequently utilized dosing strategy and probably benefit patients in the long run by exposure to more effective therapy,” McCollum said.

In ReDOS, the median overall survival (OS) was 9.0 months in the dose-escalation arm versus 5.9 months in the standard arm (P = .0943). The OS rate at 6 months (66.5% vs 49.8%) and at 12 months (34.4% vs 26.7%) favored the escalation arm.

The primary endpoint was the proportion of patients who completed 2 cycles of treatment and initiated a third. Patients in the dose-escalation arm were more likely to meet that endpoint (43% vs 24%; P = 0.281) while demonstrating improved quality-of-life parameters and experiencing less toxicity.

The FDA approved regorafenib in 2012 for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, with an anti-VEGF therapy, and, if KRAS wild-type, with an anti-EGFR therapy.

In an interview during the 2018 OncLive® State of the Science Summit™ on Gastrointestinal Cancers, McCollum, an attending oncologist at Baylor University Medical Center, discussed the need for greater use of molecular profiling, the importance of tumor sidedness when selecting a treatment regimen, and the value of maintenance therapy in patients with metastatic disease.

OncLive: Can you provide a summary of your presentation?

McCollum: We spoke about the modern-day management of colon cancer, looking at lines of therapy, progressing through different lines of therapy, and then talking about ways to manage patients who have refractory disease. The majority of the first part of the presentation focused on how to choose an appropriate frontline treatment option, then how one tries to navigate induction therapy and move into maintenance therapy.

There were a lot of different data discussed looking at the different options, incorporating things like patient preferences in terms of toxicity they might be more accepting of, and also tumor sidedness of the cancer, which is something that's come to light more recently. Along with that, there are specific side effects that we see with different monoclonal antibodies that are used in the management of colon cancer, such as VEGF- and EGFR-directed therapy.

We discussed how to segue from that active, intense regimen into this maintenance treatment, and the options available there for patients, which, helps to optimize the balance between quality of life and prolonging life.

What is your position on the use of regorafenib in metastatic disease?

We have 2 approved agents in that space: trifluridine/tipiracil (Lonsurf) and regorafenib. These 2 drugs have never been compared head-to-head, but they have each been compared in pivotal data to supportive care because that is the standard in patients with refractory disease. Both offer an advantage. Using them early enough in the course of illness is important because they can provide benefit for patients.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 14th Annual International Symposium on Melanoma and Other Cutaneous Malignancies®Apr 30, 20192.0
Oncology Consultations®: The Advancing Role of CAR T-Cell Therapies in Hematologic MalignanciesApr 30, 20191.5
Publication Bottom Border
Border Publication