Optimizing Treatment Strategies in Relapsed/Refractory Metastatic CRC - Episode 1

Continuum of Care for Metastatic CRC

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Fortunato Ciardiello, MD, PhD: Treatment of metastatic colorectal cancer has been improving since we started to do a continuum of care. That means we have the possibility of using a series of different antineoplastic drugs together, and more importantly in sequences, that allow us to treat patients for long periods to control disease progression, obtain tumor shrinkage, and extend the survival in these patients while preserving quality of life.

Therefore, continuum of care with different lines of treatment became the standard treatment for most patients with metastatic colorectal cancer. This continuum of care includes whole surgical resection or locoregional treatment, whenever necessary, of some metastatic sites, and mostly to liver metastases. Continuum of care has changed metastatic colorectal cancer from a disease that used to have a median survival time of between 6 months and 12 months only 20 years ago, to a disease in which most patients can experience a survival time across all lines of treatment, globally, of 30 to 40 months. In some groups, extension of survival is even longer.

All patients should get all the lines of treatment that are necessary to control the disease for as long as possible. In Europe, most patients are treated either in comprehensive cancer centers or in regional hospitals in which a multidisciplinary team approach allows these patients to get all the therapeutic options within a public health care system. Therefore, in most regional health care systems in Europe, when patients get the diagnosis of metastatic colorectal cancer, they are referred to a specific team of experts that will define the sequence of therapies, and if necessary, also the introduction of surgery for liver metastases when it is appropriate. There is not too much difference between treatment options if a patient goes to a large, big comprehensive cancer center or a smaller regional community hospital, at least for the big countries in Europe.

Axel Grothey, MD: We've known for a long time that patients benefit from getting access to all active agents, and this is still linked to this question of lines of therapy; first line, second line, with maintenance therapy in between. There's this perception that patients in a community setting might get fewer lines of therapy that can influence the outcome. I'm not sure about that because it's really not about academic versus community, it's more about the patient population. From my experience in the Mayo Clinic and now being in a more academically phrased community setting, there might be different patients, performance status, access to health care, etc, that might be a more determining factor than academic versus community. The goal is to keep patients exposed to all lines of treatment based on molecular parameters that we test up front. For instance, a patient with a RAS wild type, BRAF wild type situation has the chance to get 1 line of therapy more just being exposed to EGFR-antibody therapy.

Unfortunately, even in an academic or high-end community setting, not every patient will go from first line, to second line, third line treatment. I think we probably lose patients, about 20% from each line to line to line of therapy, and that is reality. That is something we are likely never going to change.

Heinz-Josef Lenz, MD, FACP: I think the unmet needs for colorectal cancer are significantly defined by the molecular characterization of colorectal cancer. We have come a long way to use and integrate biomarkers to decide the best treatment options. We all now look for KRAS mutations, BRAF mutations and microsatellite instability, which changed the selection of treatments we discuss with our patients. I think one of the biggest unmet need is the KRAS-mutated group, we still do not have treatments for this patient population when they have failed first-line treatment. I think there are some promising new targets being developed, however, we do not have standard of care treatment options for this patient population. I think another very important one is the microsatellite stable [group], where we have not successfully integrated immunotherapy for these patients to try to turn a cold tumor into a hot tumor to offer immunotherapies in combination with other targeted drugs to see significant success.

I think one of the biggest unmet needs is the Wnt pathway; 95% of colon cancers have activation in this pathway, and we still have not achieved any new drug development with any success or promising results in that arena. I think that would be a big step forward, and particularly, we would also target the colon cancer stem cells, which are ultimately responsible for the failures of our therapies.

Transcript Edited for Clarity