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First-Line mCRC Treatment Must Encompass Individualized Approach

Gina Columbus @ginacolumbusonc
Published: Wednesday, Mar 01, 2017

Axel Grothey, MD

Axel Grothey, MD

In an effort to improve patient outcomes and develop a clearer understanding of the biology of metastatic colorectal cancer (mCRC), researchers are working on more individualized approaches that will increase efficacy yet also aid in quality of life.

“We tailor our treatment approach according to the needs of the patient,” explained Axel Grothey, MD. “We utilize the different treatments we have to serve different purposes.”

Grothey lectured on frontline therapy and maintenance strategies in mCRC during the 2017 OncLive State of the Science Summit (SOSS) on Gastrointestinal Malignancies.

One innovative approach was discussed during the 2017 Gastrointestinal Cancers Symposium, where results of a randomized phase II trial demonstrated that the addition of vemurafenib (Zelboraf) to the standard combination of irinotecan and cetuximab (Erbitux) prolonged progression-free survival (PFS) in patients with BRAF-mutant mCRC.

In the study, which evaluated 106 patients, the median PFS improved from 2.0 months in the arm randomized to cetuximab and irinotecan to 4.4 months in patients assigned to the combination plus vemurafenib. Future analyses will include overall survival.

In an interview with OncLive during the SOSS meeting, Grothey, a medical oncologist at Mayo Clinic, expressed the need for tailoring treatments for patients with mCRC in the first-line setting, the debate over tumor sidedness in mCRC, and what ongoing research in the field might reveal over the next year.

OncLive: Please provide an overview of your presentation on mCRC.

Grothey: There are a great variety of different agents that we have available right now. We need to make sense of which combinations we use for which clinical setting. Not every patient needs the same treatment, and we’ve known this for quite some time.

Obviously, individualized therapy did not start with the KRAS mutational analysis. We need to tailor our therapies according to patient needs, and we make use of treatment combinations that we have available in our armamentarium.

Before we start treatment for a patient with palliative intent, we have to keep in mind that the goal of palliation is to keep patients alive with a good quality of life for as long as possible. Treatment intensity is very important; first-line therapy is the longest time the patient is on therapy. When I talk to patients, I explain treatment algorithms and plan for the future because metastatic disease patients will more or less be on therapy for the rest of their life with breaks in between. I tell them, “This is not a sprint; it’s a marathon.”

We should not burn bridges early on by blasting a patient with too much treatment unnecessarily; we tailor treatment according to patient needs. In an elderly patient with low-volume disease, we don’t need a response to make a difference. Patients can benefit from something as easy as capecitabine/bevacizumab (Avastin) versus a more aggressive combination therapy. For other patients who have disease that is symptomatic where we need a response, we might need a chemotherapy triplet. BRAF-mutant tumors need to be counteracted by more aggressive therapy. This all needs to be taken into account.

What is the importance of molecular testing in this field?

We do test patients’ tumors routinely for KRAS, NRAS, and HRAS mutations. We know that, in patients who have activating mutations, these genes do not benefit from EGFR antibodies. Cetuximab and panitumumab (Vectibix) do not work in these BRAF V600E-mutant tumors. We refine the treatment approach in the first-line setting according to individual patient characteristics, molecular tumor characteristics and, most recently, sidedness. 

We know that right-sided and left-sided tumors have different prognoses. Right-sided tumors do poorer than left-sided tumors, but there is also a predictive component in all of this—not just prognostic. The right-sided tumors do not benefit from EGFR therapy and that is on top of the mutational analysis we are doing. We have right-sided tumors that are RAS wild-type and BRAF wild-type.

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