Scott Kopetz, MD, PhD

Scott Kopetz, MD, PhD, professor in the Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the next steps following the phase 3 BEACON CRC trial (NCT02928224) of encorafenib (Braftovi) plus cetuximab (Erbitux) with or without binimetinib (Mektovi) compared with irinotecan (Camptosar) or FOLFIRI (folinic acid, fluorouracil, and irinotecan)plus cetuximab in patients with BRAF V600E metastatic colorectal cancer (mCRC).

The overall survival data of the participating patients are mature, and Kopetz says he and the other investigators are hoping to further explore the potential subsets of patients that may benefit from 1 therapy over the other. There were trends showing that patients with more aggressive disease, higher inflammatory states, or poor performance status may derive more benefit with the addition of the MEK inhibitor, but these trends are still in the exploratory stage.

Another step in this trial will be understanding the mechanism of resistance using the circulating tumor DNA data and profiling the tumor with the RNA signatures to understand if there are subsets of patients that may derive more benefit from the treatment than others, says Kopetz.

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Scott Kopetz, MD, PhD, discusses the next steps following the phase 3 BEACON CRC trial of encorafenib plus cetuximab with or without binimetinib compared with irinotecan or FOLFIRI plus cetuximab in patients with BRAF V600E metastatic colorectal cancer.

Updated Survival Data from BEACON CRC Lead to More Specific Questions

Scott Kopetz, MD, PhD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the combination of regorafenib (Stivarga) and nivolumab (Opdivo) for patients with colorectal cancer (CRC).

Kopetz says that this combination is a treatment of interest in the CRC landscape right now based on an early phase study that was done in Japan, which showed a high response rate of above 30%. This included patients with metastatic CRC who were microsatellite stable.

There are other similar ongoing phase II trials from single institutions as well as multicenter studies to further evaluate these findings and confirm the data that has been published so far, and Kopetz says he is looking forward to seeing these data published. He believes that there is a lot of hope from physicians in this setting that the regorafenib and nivolumab combination will be beneficial for patients with CRC. There is also an awareness from these physicians that there will need to be more studies to replicate the data in a larger population to better define the benefits of the combination.

Scott Kopetz, MD, PhD, discusses&nbsp;the combination of regorafenib and nivolumab for patients with colorectal cancerthe combination of regorafenib and nivolumab for patients with colorectal cancer.

Exploring Regorafenib and Nivolumab as Treatment for Colorectal Cancer

Scott Kopetz, MD, PhD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, discusses the treatment of patients with colorectal cancer (CRC) and how it differs from other cancer regimens.

Kopetz says that the data in the CRC trials is looking at how to optimally treat patients. Patients with a

V600E mutation should be treated in a different manner than other types of cancer, and that aggressive chemotherapy may be effective at first, but the duration of benefit from standard cytotoxic chemotherapy is less than what is seen in other patients with cancer, according to Kopetz.

mutation directly is a key part of deciding on treatment. Kopetz thinks that this patient population is a distinct entity compared to others in oncology on a biologic level because of the precursor lesions, the polyps in the tumors, and the carcinogenic pathways activated are all different. The clinical outcomes are also different for patients with

V600E-mutated CRC, which makes it a distinct subgroup of CRC.

Scott Kopetz, MD, PhD, discusses the treatment of patients with colorectal cancer and how it differs from other cancer regimens.

How BRAF V600E-Mutated CRC is Treated Differently Than Other Cancers

Scott Kopetz, MD, PhD, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the results of the phase III BEACON CRC study, which was presented at the 2020 Gastrointestinal Cancers Symposium.

The trial, which evaluated encorafenib (Braftovi) plus cetuximab (Erbitux) with or without binimetinib (Mektovi) in patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), met its primary end point. Both experimental arms had a higher response rate compared with the standard of care. The response rate was 26% with the triplet combination, 20% with the doublet, and 2% in the control arm, Kopetz says.

The BEACON CRC trial led to the question of how treatment with encorafenib plus cetuximab with/without binimetinib will impact the quality of life in patients with BRAF V600E-mutant CRC. The presentation of these data at the 2020 GI Cancers Symposium focused on the question of how these results can impact the treatment of patients.

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Scott Kopetz, MD, PhD, discusses the results of the phase III BEACON CRC study, which was presented at the 2020 Gastrointestinal Cancers Symposium.

Encorafenib Combination Improves Responses in BRAF V600E-Mutant CRC

Scott Kopetz, MD, PhD, medical oncologist, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, explains how prognoses for patients with colorectal cancer (CRC) differ based on whether their cancer is left-sided or right-sided and discusses how knowledge of these differences have led to the development of more agents to treat both groups of patients.

Right-sided CRC results in a poor prognosis overall. Using standard therapies, these patients generally have lower progression-free survival (PFS) and shorter durations of response, says Kopetz. Right sidedness may also lead to recurrence after liver resection for metastases. Obtaining more knowledge about prognoses for right-sided disease has raised questions in the field related to how right-sided tumors should be treated and whether or not it has an impact on chemotherapy.

Studies have shown that targeted therapies don&rsquo;t have the same activity in right-sided CRC as they do in left-sided CRC. Research around 2 EGFR-based therapies, cetuximab (Erbitux) and panitumumab (Vectibix), has shown that patients with tumor of the right side of the colon don&rsquo;t respond as well to EGFR-targeted therapies as those with left-sided tumors, even if they do not have

mutations. This is what impacts PFS rates among patients with right-sided CRC treated with bevacizumab (Avastin)based therapies. When compared with placebo, treatment with targeted therapies do not improve responses in right-sided tumors in later lines of treatment.

For left-sided CRC, patients do respond to EGFR-targeted therapies and show better responses compared with VEGF therapy.

Scott Kopetz, MD, PhD, explains how prognoses for patients with colorectal cancer differ based on whether their cancer is left-sided or right-sided and discusses how knowledge of these differences have led to the development of more agents to treat both groups of patients.

Scott Kopetz, MD, PhD | Authors

Articles

Updated Survival Data from BEACON CRC Lead to More Specific Questions

Exploring Regorafenib and Nivolumab as Treatment for Colorectal Cancer

How BRAF V600E-Mutated CRC is Treated Differently Than Other Cancers

Encorafenib Combination Improves Responses in BRAF V600E-Mutant CRC

Differences in Prognoses for Patients With Right-Sided or Left-Sided Colorectal Cancer