Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses a study exploring the various molecular characteristics of colorectal cancer (CRC) tumors.

For the study, researchers were trying to molecularly characterize the types of CRC tumors to individualize treatment, Braghiroli says. Patients were selected if they were found to harbor an 

 mutation from 2008 to 2015 and were treated at Memorial Sloan Kettering Cancer Center. This included 87 patients; 3 were excluded because they harbored 

 mutations. This population was then compared with clinical characteristics, molecular characteristics, and outcomes to treatment with those who harbored a 

Outside of this trial, there have been several studies focused on immunotherapy, which is very exciting, she adds.

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Dr. Braghioli on Molecular Characterization of CRC Tumors

Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses clinical characteristics and outcomes of patients with metastatic colorectal cancer (CRC) harboring NRAS mutations.

Previous studies have shown that patients with right-side tumors have worse outcomes than patients with left-side tumors, says Braghiroli.

The CALGB/SWOG 80405 phase III trial demonstrated that survival outcomes in patients with KRAS wild-type metastatic mCRC were significantly longer among those with tumors originating on the left versus the right side of the colon.

In the analysis, the primary tumor location of all patients enrolled in the 80405 trial was identified either right (293), left (732), transverse (66), or uncertain (46). Across both treatment arms, the median overall survival (OS) was 19.4 months (95% CI, 16.7-23.6) among patients with right-sided tumors compared with 33.3 months (95% CI, 31.4-35.7) for patients with left-sided tumors (HR, 1.60; 95% CI, 1.37-1.86; P <.001). Progression-free survival (PFS) was 8.9 versus 11.5 months, respectively (HR, 1.26; 95% CI, 1.096-1.453; P = .002).

Braghiroli presented data at the recent 2016 ESMO Congress, which examined the clinical characteristics and associated outcomes of patients with mCRC who were also harboring NRAS mutations. She and her colleagues found that NRAS-mutant mCRC is an aggressive subset of CRC with worse overall survival outcomes than that for patients with RAS wild-type tumors or KRAS-mutant mCRC.

Interestingly, this subgroup of patients with NRAS-mutant mCRC tend to have increased left-sided colon primary tumors, and these patients may also have a distinct molecular pathogenesis. So the correlation between better prognosis and left sided tumors is still up for debate, says Braghiroli.

​Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses clinical characteristics and outcomes of patients with metastatic colorectal cancer (CRC) harboring NRAS mutations.

Dr. Maria Ignez Braghiroli on Impact of Tumor Side in mCRC

Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses what the current treatment landscape looks like for patients with colorectal cancer (CRC), as well as what the future may hold.

 gene occur in 2% of metastatic colorectal cancer (mCRCs) and are now being identified in routine clinical practice by extended 

 genotyping. The clinical implications of 

 mutations, and whether these tumors behave similarly to 

-mutant mCRC, are not clear at the present time.

As of now, according to Braghiroli, oncologists know that anti-EGFR medications do not work for 

-mutant patients, who represent a much smaller subset of those with CRC—approximately 3% to 7%.

Braghiroli presented data at the recent 2016 ESMO Congress, which closely examined the clinical characteristics and associated outcomes of patients with mCRC who were also harboring 

 mutations. She and her colleagues found that 

-mutant mCRC is an aggressive subset of CRC with worse overall survival outcomes than that for patients with 

Future treatments in this space, says Braghiroli, will likely include immunotherapy agents. One such ongoing study will be looking at whether MK-3475—an antibody that blocks negative signals to T cells&mdash;demonstrates antitumor activity in 3 different patient populations. These include patients with microsatellite-instability (MSI)-positive colon cancer, patients with MSI-negative colon cancer, and patients with other MSI-positive cancers.

Most of these immunotherapies are still in early-phase clinical testing for CRC, but their efficacy in other cancer types suggests that they may ultimately prove useful for this disease as well. Moreover, according to Braghiroli, some ongoing studies are looking further into fecal identification and blood identification of tumor cells to hopefully identify a tumor earlier.

Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses what the current treatment landscape looks like for patients with colorectal cancer, as well as what the future may hold.


Dr. Braghiroli on the Current and Future Treatment Landscape in CRC

Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses the ways in which treatment can be individualized for patients with colorectal cancer (CRC) depending on the mutations they may harbor.

For example, explains Braghiroli, patients with 

-mutated CRC do not seem to respond positively to anti-EGFR medications. Moreover, patients with 

-mutated disease generally tend to have a worse prognosis.

Multiple studies have focused on the respective efficacies of BRAF and MEK inhibitors, MEK inhibitors, as well as combinations of these agents. Overall, says Braghiroli, these various subgroups of patients will require individualized treatment approaches.

Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses the ways in which treatment can be individualized for patients with colorectal cancer depending on the mutations they may harbor.

Dr. Braghiroli on Individualization of Treatment in CRC

Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses clinical characteristics and outcomes of patients with 

-mutant metastatic colorectal cancer (mCRC) during an interview at the 2016 ESMO Congress.

-mutant mCRC is an aggressive subset of mCRC, and patients typically experience worse overall survival than patients with 

-mutant mCRC tend to have increased left-sided colon primary tumors, and these patients may also have a distinct molecular pathogenesis.

Maria Ignez Braghiroli, MD, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses clinical characteristics and outcomes of patients with NRAS-mutant metastatic colorectal cancer (mCRC) during an interview at the 2016 ESMO Congress.

Maria Ignez Braghiroli, MD

Articles

Dr. Braghioli on Molecular Characterization of CRC Tumors

Dr. Maria Ignez Braghiroli on Impact of Tumor Side in mCRC

Dr. Braghiroli on the Current and Future Treatment Landscape in CRC

Dr. Braghiroli on Individualization of Treatment in CRC

Dr. Braghiroli on Clinical Characteristics of NRAS-Mutant CRC