Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses targeted strategies in 

-mutant metastatic colorectal cancer (mCRC).

Many therapeutic advances have been made for patients with 

 V600E—mutant mCRC which accounts for approximately 10% of all mCRC cases, says Cercek. The mutation is associated with a worse prognosis and confers lack of benefit to cytotoxic chemotherapy. Data from the phase III BEACON CRC study showed a significant improvement in overall survival with the 3-drug combination of encorafenib (Braftovi), binimetinib (Mektovi), and cetuximab (Erbitux) versus encorafenib/cetuximab and investigator’s choice of chemotherapy in these patients. However, although the triplet performed statistically better than the control, it also resulted in more toxicity, says Cercek.

In 2018, the FDA granted a breakthrough therapy designation to the triplet for the treatment of patients with 

 V600E—mutant mCRC who have progressed on ≤2 prior lines of therapy.

Videos

Andrea Cercek, MD, discusses targeted strategies in BRAF-mutant metastatic colorectal cancer.

Dr. Cercek on Targeted Strategies in BRAF-Mutant mCRC

Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the impact of tumor sidedness on frontline treatment decisions in metastatic colorectal cancer (mCRC).

Tumor sidedness influences frontline treatment decisions in mCRC, says Cercek. Several retrospective analyses have shown that patients with right-sided tumors, as well as those with 

 wild-type tumors, do not benefit from anti-EGFR therapy. These patients do, however, benefit from anti-VEGF therapy in combination with cytotoxic therapy, says Cercek. Conversely, patients with left-sided tumors benefit from anti-EGFR therapy, adds Cercek.

 wild-type tumors have a more aggressive biology and confer lack of response to targeted therapy versus left-sided tumors is unknown, concludes Cercek.

Dr. Cercek on the Impact of Tumor Sidedness on Frontline Treatment in mCRC

Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the need for treatment options in 

-mutated metastatic colorectal cancer (mCRC).

 mutations comprise about 50% of patients with mCRC. Patients with a 

 mutation have 1 less therapeutic option because they cannot be treated with anti-EGFR therapy, said Cercek. There have been poor responses in the mCRC setting of 

-mutated tumors with certain treatments, such as cetuximab (Erbitux) and panitumumab (Vectibix).

Emerging studies will focus on helping this particular patient population, concludes Cercek.

Andrea Cercek, MD, discusses the need for treatment options in KRAS-mutated metastatic colorectal cancer (mCRC).

Dr. Cercek on the Need for Treatment Options in KRAS-Mutated mCRC

Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the importance of molecular testing in colorectal cancer (CRC).

Molecular markers play a key role in the treatment of patients with CRC, says Cercek.

Patients whose tumors are microsatellite instable (MSI) or mismatch repair deficient (dMMR) have a genetic predisposition to Lynch syndrome, explains Cercek.

All patients with CRC should be tested for MSI/dMMR upon diagnosis or before starting second-line therapy, says Cercek. A subset of these patients could experience significant benefit with immunotherapy.

Additionally, targeted therapy may be given to patients with actionable mutations such as 

 in the first-line or relapsed/refractory settings, concludes Cercek.

Andrea Cercek, MD, discusses the importance of molecular testing in colorectal cancer.

Dr. Cercek on the Importance of Molecular Testing in CRC

Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses chemotherapy resistance in mismatch repair deficient (dMMR) rectal cancer.

Locally advanced rectal cancer is typically treated with a tri-modality therapy; this approach includes chemoradiation, surgery, and chemotherapy. It was recently discovered that moving 5-fluorouracil and oxaliplatin-based chemotherapy upfront, and following with chemoradiation and surgery can improve patient compliance with chemotherapy. This compliance, Cercek says, theoretically improves the treatment of micrometastatic disease as well as rates of complete response. This approach has now been incorporated into the guidelines as the standard of care for patients with locally advanced rectal cancer in the United States.

However, it was discovered that patients with dMMR or microsatellite instability-high rectal cancer did not respond well to chemotherapy upfront, he adds. Given this anecdotal evidence, investigators initiated a study to evaluate the sensitivity of dMMR rectal cancer to chemotherapy. In the study, the baseline characteristics, treatment modalities, and clinical outcomes of patients with dMMR rectal cancer were retrospectively reviewed.

Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses chemotherapy resistance in mismatch repair deficient rectal cancer.
 

Dr. Cercek on Chemotherapy Resistance in dMMR Rectal Cancer

Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses induction chemotherapy in patients with mismatch repair (MMR) deficient rectal cancer.

The responsiveness to chemotherapy remains uncertain in the population of patients with rectal cancer who are MMR deficient. There are data that have shown that patients who have MMR deficient colorectal adenocarcinoma do not respond to chemotherapy in the metastatic setting.

In a study of patients with Lynch syndrome and MMR deficient rectal cancer, 26% of those who received neoadjuvant chemotherapy with either FOLFOX or capecitabine and oxaliplatin had disease progression. The majority of these patients harbored germline mutations in the MMR genes. This is concerning for rectal cancer, Cercek says, because induction chemotherapy usually is successful in patients.

Cercek says that these data highlight the need for immunohistochemistry to be checked in patients with locally advanced rectal cancer, because a small portion of them have MMR deficiency. Additionally, if a patient has known Lynch syndrome or is microsatellite instability-high, they should not receive neoadjuvant chemotherapy.

Andrea Cercek, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses induction chemotherapy in patients with mismatch repair deficient rectal cancer.
 

Andrea Cercek, MD

Articles

Dr. Cercek on Targeted Strategies in BRAF-Mutant mCRC

Dr. Cercek on the Impact of Tumor Sidedness on Frontline Treatment in mCRC

Dr. Cercek on the Need for Treatment Options in KRAS-Mutated mCRC

Dr. Cercek on the Importance of Molecular Testing in CRC

Dr. Cercek on Chemotherapy Resistance in dMMR Rectal Cancer

Dr. Cercek on Induction Chemotherapy in Mismatch Repair Deficient Rectal Cancer