Atrayee Basu-Mallick, MD, a medical oncologist at Sidney Kimmel Cancer Center, and clinical assistant professor at the Thomas Jefferson University, highlights established and emerging biomarker-directed therapies in colorectal cancer (CRC).

Approximately 40% of patients with CRC have 

 wild-type disease and are able to receive treatment with established therapies such as cetuximab (Erbitux) and panitumumab (Vectibix), Basu-Mallick says. Additionally, approximately 8% of patients have a 

 mutation, the majority of whom have poor outcomes. For patients who have 

 wild-type disease, the median survival is about 13 months, Basu-Mallick adds.

 mutation are relatively chemotherapy refractory, or have short responses to chemotherapy. Due to this, a combination of encorafenib (Braftovi) plus cetuximab or a triplet regimen comprised of encorafenib, cetuximab, and binimetinib (Mektovi) can be utilized. However, the triplet regimen is not frequently used, as the outcomes achieved with the 3-drug regimen have proven to be similar to those seen with the doublet regimen, Basu-Mallick explains. For patients who have HER2-positive disease, trastuzumab (Herceptin) plus pertuzumab (Perjeta), as well as trastuzumab plus lapatinib (Tykerb), have elicited a favorable overall response rate (ORR).

The phase 2 DESTINY-CRC01 trial (NCT03384940), which examined fam-trastuzumab deruxtecan-nxki (Enhertu), was unique in that it enrolled patients who were previously treated with an anti-HER2 therapy, Basu Mallick says. It was the first trial in which patients with CRC who had previously received HER2-targeted therapy could receive further HER2-directed treatment, according to Basu-Mallick. The ORR observed with the antibody-drug conjugate in patients who had previously received treatment was similar to that reported in the overall patient population, at 43.8% and 45.3%, respectively, Basu-Mallick concludes.

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Atrayee Basu-Mallick, MD, highlights established and emerging biomarker-directed therapies in colorectal cancer.

Dr. Basu-Mallick on Established and Emerging Biomarker-Directed Therapies in CRC

Atrayee Basu-Mallick, MD, a medical oncologist at Sidney Kimmel Cancer Center and clinical assistant professor at Thomas Jefferson University, discusses the importance of clinical research examining the role of circulating tumor DNA (ctDNA) in patients with colorectal cancer (CRC).

In early-stage CRC, years have passed without significant development in this area, according to Basu-Mallick. It is important to encourage patient enrollment on studies that are examining the role of ctDNA in this patient population, such as the phase 2/3 NRG-GI005 (NCT04068103) and the phase 3 NRG-GI008 trial (NCT04120701), says Basu-Mallick.

Currently, the use of ctDNA in a predictive manner is not ready for prime time, Basu-Mallick explains. Having more patients enroll to these clinical trials could shed light on how important ctDNA data can be converted into a prognostic marker, Basu-Mallick concludes.

Atrayee Basu-Mallick, MD, discusses the importance of clinical research examining the role of circulating tumor DNA in patients with colorectal cancer.


Dr. Basu-Mallick on the Importance of Clinical Research Examining ctDNA in CRC

Atrayee Basu-Mallick, MD, a medical oncologist at Sidney Kimmel Cancer Center and clinical assistant professor at Thomas Jefferson University, discusses factors to consider when selecting a frontline HER2-directed treatment regimen for patients with colorectal cancer (CRC). 

HER2-directed therapies have demonstrated response rates ranging from 30% to 50% in patients with CRC, says Basu-Mallick. Current HER2-targeted therapies are reserved for patients who are 

 wild-type because data have not shown the utility of these therapies in patients who harbor 

 mutations. Patients with HER2-positive, 

 wild-type disease should receive HER2-directed therapy rather than traditional third- or fourth-line options, such as regorafenib (Stivarga) or trifluridine/tipiracil (TAS-102; Lonsurf), because the traditional options have demonstrated very low response rates in this patient population, Basu-Mallick explains.

In the frontline setting, the combinations of trastuzumab (Herceptin) and pertuzumab (Perjeta), trastuzumab and lapatinib (Tykerb), or trastuzumab and tucatinib (Tukysa) are valid options for patients, says Basu-Mallick. The toxicity profiles associated with each regimen may inform which combination is best for which patients, Basu-Mallick adds. Additionally, fam-trastuzumab deruxtecan-nxki (Enhertu) should be reserved for patients who progress on initial HER2-directed therapy because that was the setting the antibody-drug conjugate was evaluated in, concludes Basu-Mallick.

Atrayee Basu-Mallick, MD, discusses factors to consider when selecting a frontline HER2-directed treatment regimen for patients with colorectal cancer.  



Dr. Basu-Mallick on Selecting Frontline HER2-Directed Therapy in CRC 

Atrayee Basu-Mallick, MD, a medical oncologist at Sidney Kimmel Cancer Center and clinical assistant professor at Thomas Jefferson University, discusses the role of circulating tumor DNA (ctDNA) in patients with colorectal cancer (CRC).

In the future, the escalation or de-escalation of care could be based on ctDNA, as it appears to be a reliable prognostic biomarker, Basu-Mallick says. Additionally, ctDNA could help to examine new agents in this patient population by achieving quicker end points in clinical trials, Basu-Mallick notes.

Currently, the ongoing phase 2/3 NRG-GI005 or COBRA trial (NCT04068103) is examining treatment escalation based on ctDNA for patients with stage IIA disease who are not eligible for adjuvant therapy, Basu-Mallick explains. Additionally, the ongoing NRG-GI008 trial (NCT04120701) will enroll low-risk patients with stage III disease and evaluate both therapy escalation for those who are ctDNA positive, and de-escalation for those who are ctDNA negative, Basu-Mallick concludes.

Atrayee Basu-Mallick, MD, discusses the role of circulating tumor DNA in patients with colorectal cancer.


Atrayee Basu-Mallick, MD

Articles

Dr. Basu-Mallick on Established and Emerging Biomarker-Directed Therapies in CRC

Dr. Basu-Mallick on the Importance of Clinical Research Examining ctDNA in CRC

Dr. Basu-Mallick on Selecting Frontline HER2-Directed Therapy in CRC

Dr. Basu-Mallick on Ongoing Research With ctDNA in CRC