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

Maria Ignez Braghiroli, MD
Published: Tuesday, Oct 25, 2016



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.

Activating, hotspot mutations in the NRAS gene occur in 2% of metastatic colorectal cancer (mCRCs) and are now being identified in routine clinical practice by extended RAS genotyping. The clinical implications of NRAS mutations, and whether these tumors behave similarly to KRAS-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 KRAS- or NRAS-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 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.

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—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 (CRC), as well as what the future may hold.

Activating, hotspot mutations in the NRAS gene occur in 2% of metastatic colorectal cancer (mCRCs) and are now being identified in routine clinical practice by extended RAS genotyping. The clinical implications of NRAS mutations, and whether these tumors behave similarly to KRAS-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 KRAS- or NRAS-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 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.

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—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.

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