Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, discusses treatment strategies for patients with different molecular subtypes of metastatic colorectal cancer (mCRC). 

-mutant mCRC is typically associated with a poor prognosis; however, targeted treatment regimens such as vemurafenib (Zelboraf), irinotecan, and cetuximab (Erbitux), as well as encorafenib (Braftovi), binimetinib (Mektovi), and cetuximab have both shown benefit in later-line settings for this patient population. 

Additionally, patients with rectal cancer who harbor 

 amplifications may benefit from HER2-targeted therapies in later-line settings, adds Weinberg. 

Patients with microsatellite instability—high tumors account for about 4% of all patients with mCRC, says Weinberg. Treatment with anti–PD-1 therapies such as pembrolizumab (Keytruda) or nivolumab (Opdivo), in combination with anti–CTLA4 therapies like ipilimumab (Yervoy) appear to be of benefit. 

 fusions appear to respond to larotrectinib (Vitrakvi) and entrectinib (Rozlytrek). Though rare, it is important to be aware of these fusions, concludes Weinberg. 

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Benjamin Weinberg, MD, discusses treatment strategies for patients with different molecular subtypes of metastatic colorectal cancer. 
 

Dr. Weinberg on Targeted Therapies for Molecular Subsets of mCRC

Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, discusses the importance of broad molecular profiling in patients with gastrointestinal (GI) cancers.

Moving forward, clinicians are going to have to be more persistent about performing genetic testing in patients with these various tumor types. There are many genetic alterations that are highly rare, but if detected, they can be paired with effective therapies. 

 is a good example of this, Weinberg says. Although these mutations only appear in approximately 1% of patients with GI cancers, physicians still need to look for them in every patient.

For example, larotrectinib (Vitrakvi) was approved by the FDA in November 2018 for use in patients with solid tumors that harbor 

 fusions, and this drug is essentially a “silver bullet” for these patients. There are low rates of 

 expression and microsatellite instability, as well, but these also have associated treatment options.

Other important molecular defects are homologous recombination deficiency and 

 mutations, which can be inherited or acquired de novo. These patients have a higher likelihood of responding to platinum-based chemotherapy as well as PARP inhibitors, says Weinberg. As such, future research will be geared toward bringing PARP inhibitors to greater prominence in this space, Weinberg notes.

Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, discusses the importance of broad molecular profiling in patients with gastrointestinal cancers.

Dr. Weinberg on Broad Molecular Profiling in GI Cancers

Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, discusses the use of FOLFIRINOX in older patients with metastatic pancreatic cancer.

Historically, FOLFIRINOX has been reserved for younger patients with a good performance status. However, in February 2019, investigators at The University of Texas MD Anderson Cancer Center published a study in the 

 on the use of FOLFIRINOX in patients with unresectable pancreatic cancer aged 75 or older. Although the study was a single-center retrospective analysis, it showed similar survival outcomes to the initial PRODIGE trial, which served as the basis for the regimen’s FDA approval.

In practice, Weinberg tends to dose reduce to make the regimen more tolerable for all patients. Additionally, white blood cell growth factor support is often used for patients who have low blood counts on the regimen.

In addition to FOLFIRINOX, the combination of gemcitabine and nab-paclitaxel (Abraxane) is also approved by the FDA for frontline use. However, in the trials that led to their approvals, both regimens were compared with single-agent gemcitabine. There are no head-to-head data comparing the 2 regimens. Moving forward, physicians will need access to better tests to determine which patient should receive a 5-fluorouracil—based regimen and which patient should receive a gemcitabine-based regimen, concludes Weinberg.

Benjamin Weinberg, MD

Articles

Dr. Weinberg on Targeted Therapies for Molecular Subsets of mCRC

Dr. Weinberg on Broad Molecular Profiling in GI Cancers

Dr. Weinberg Discusses the Use of FOLFIRINOX in Older Patients With Metastatic Pancreatic Cancer