Dr Boland on the Emergence of KRAS G12C Inhibitors in mCRC

Patrick Boland, MD, medical oncologist, Gastrointestinal Oncology team, Rutgers Cancer Institute of New Jersey, RWJBarnabas Health, discusses the development of therapeutic strategies targeting 

 G12C mutations in colorectal cancer (CRC).

 G12C inhibitors have marked a significant development in the treatment of patients with varying tumor types, Boland begins. This novel drug class have already demonstrated efficacy in lung cancer and recently hasshown activity in CRC in the phase 3 CodeBreaK 300 trial (NCT05198934), he states.

The multicenter, open-label investigation evaluated the efficacy of the 

 G12C inhibitor sotorasib (Lumakras) in combination with the EGFR inhibitor panitumumab (Vectibix) for patients with mCRC harboring 

 G12C mutations who were chemorefractory. The study, which was 

, demonstrated that the combination of panitumumab and sotorasib at both dose levels significantly improved progression-free survival (PFS) compared with investigator's choice of therapy: trifluridine/tipiracil (TAS-102) or regorafenib, Boland reports.

Patients randomly assigned to receive 960 mg of sotorasib/panitumumab achieved a median PFS of 5.6 months, while those receiving 240 mg had a median PFS of 3.9 months. In contrast, the investigator's choice arm had a median PFS of 2.2 months. The hazard ratios for disease progression or death were 0.49 (95% CI, 0.30-0.80; 

 = .006) for the 960-mg sotorasib/panitumumab arm and 0.58 (95% CI, 0.36-0.93; P = .03) for the 240-mg sotorasib/panitumumab arm, both favoring the combination therapies. Improvements in disease control rates were also observed. The median follow-up for the analysis was 7.8 months (range, 0.1-13.9) and the data cutoff date was June 19, 2023.

Although the study wasn't specifically powered for overall survival, the preliminary results appear promising and mature follow-up data is anticipated, Boland notes. Based on these data, panitumumab plus sotorasib could emerge as a new option for patients with 

 G12C-mutated CRC in the future, Boland says. These encouraging results in CRC also underscore the potential of KRAS G12C inhibitors as a valuable addition to the therapeutic armamentarium in mCRC, he concludes.

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Patrick Boland, MD, discusses the development of therapeutic strategies targeting KRAS G12C mutations in colorectal cancer.
 

Patrick Boland, MD, medical oncologist, member of the gastrointestinal oncology team, active member of the NCI National Clinical Trial Network, discusses therapeutic options for patients with patients with liver-only metastatic colorectal cancer (mCRC).

Treatment options keep expanding for patients whose disease is not initially resectable, according to Boland. The use of triplet chemotherapy regimens has increased in recent years, and regimens such as FOLFOXIRI or FOLFIRINOX have induced high response rates in this population, Boland adds. 

Furthermore, data have shown that the addition of bevacizumab (Avastin) to FOLFOX has resulted in improved response rates and can protect the liver in patients with liver-only mCRC, Boland adds. As more is learned about these therapies and more options become available, the challenge will be determining the optimal amount and duration of these agents, Boland concludes. 

Patrick Boland, MD, discusses therapeutic options for patients with patients with liver-only metastatic colorectal cancer.

Dr. Boland on Leveraging Triplet Chemo Regimens in Non-Resectable Liver-Only mCRC 

Patrick Boland, MD, medical oncologist, member, Gastrointestinal Oncology team, Rutgers Cancer Institute of New Jersey, RWJBarnabas Health, discusses determining when to utilize up-front perioperative chemotherapy for patients with colorectal cancer (CRC) with liver metastases.

Initial considerations for up-front treatment selection in patients with CRC include assessing disease involvement in the liver, Boland says. Additionally, it is important to determine whether the patient’s disease is synchronous or metachronous. Mutational status is also important to assess because the presence of 

 mutations confers poor prognosis, Boland explains. It is also critical to determine whether the primary tumor is intact or resected and whether it is node positive, Boland adds. 

Although data are not conclusive as to whether up-front perioperative chemotherapy improves long-term outcomes, it is the preferred treatment regimen for patients with high-risk disease, even if they are resectable, Boland explains. However, it is important to try to limit the chemotherapy to 2 to 3 months and implement frequent scans ever 6 to 8 weeks to reassess the tumors. 

Notably, this method requires up-front visitation to a hepatobiliary surgeon to determine whether techniques such as portal vein embolization can be employed, Boland concludes. 

Patrick Boland, MD, discusses determining when to utilize up-front perioperative chemotherapy for patients with colorectal cancer with liver metastases.  



Dr. Boland on Determining When to Utilize Up-front Perioperative Chemotherapy in CRC 

Patrick Boland, MD, medical oncologist, member of the gastrointestinal oncology team, active member of the NCI National Clinical Trial Network, discusses the utility of circulating tumor DNA (ctDNA) in patients with metastatic colorectal cancer (CRC).

The emergence of ctDNA represents the future in metastatic CRC, according to Boland, who adds that this has been utilized in the gastrointestinal space and in other cancers. Multiple studies show that the presence of ctDNA after surgery is a poor prognosticator, and its absence is a good prognosticator, Boland says. 

Randomized studies are needed to demonstrate how to best utilize ctDNA and whether patients who are negative could omit chemotherapy, given there is not a proven survival benefit with post-operative chemotherapy, Boland adds. Moreover, there may be potential to escalate therapy for those with ctDNA positivity to improve long-term outcomes, Boland adds. The hope is that ongoing studies will address remaining questions, Boland concludes. 

Patrick Boland, MD, discusses the utility of circulating tumor DNA in patients with metastatic colorectal cancer.

Patrick Boland, MD

Articles

Dr Boland on the Emergence of KRAS G12C Inhibitors in mCRC

Dr. Boland on Leveraging Triplet Chemo Regimens in Non-Resectable Liver-Only mCRC

Dr. Boland on Determining When to Utilize Up-front Perioperative Chemotherapy in CRC

Dr. Boland on Efforts Underway to Optimize the Utility of ctDNA in CRC