E. Gabriela Chiorean, MD, FASCO, is the clinical director of the GI Medical Oncology Program, professor in the Clinical Research Division, and affiliate investigator in the Translational Science and Therapeutics Division at Fred Hutchinson Cancer Center. She is also a professor of medicine at the University of Washington and director of the Clinical Research GI Oncology Program at the University of Washington/Fred Hutch.

Dr Chiorean on Encorafenib Plus Cetuximab for BRAF V600E–Mutated mCRC

“Our patients need any help we can provide, as fast as possible, for better outcomes starting with [the] first-line [setting] because chemotherapy alone is simply not sufficient.”

E. Gabriela Chiorean, MD, FASCO, clinical director, GI Medical Oncology Program, professor, Clinical Research Division, and affiliate investigator, Translational Science and Therapeutics Division Fred Hutchinson Cancer Center; professor, medicine, University of Washington; director, Clinical Research GI Oncology Program, University of Washington/Fred Hutch, discusses the significance of the FDA approval of encorafenib (Braftovi) plus cetuximab (Erbitux) and chemotherapy for patients with 

 V600E–mutated metastatic colorectal cancer (mCRC).

the FDA granted accelerated approval to encorafenib plus cetuximab and mFOLFOX6

 (fluorouracil, leucovorin, and oxaliplatin) for the treatment of patients with mCRC harboring a 

 V600E mutation, as detected by an FDA-approved test.

 V600E–mutated CRC have had limited targeted therapy options, with encorafenib plus cetuximab available only in the second-line setting following disease progression on standard chemotherapy, Chiorean begins. However, 

V600E–mutated CRC is characterized by aggressive tumor biology, with poor overall survival (OS) outcomes, she says. Even with intensive chemotherapy regimens, such as FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) plus bevacizumab (Avastin), the median OS in this population remains shorter than 18 months, she notes.

The FDA approval of encorafenib plus cetuximab and mFOLFOX6 as a first-line regimen in this population represents a significant advancement in the treatment paradigm, Chiorean emphasizes. This development highlights the critical need for rapid genomic profiling at the time of diagnosis to identify 

 mutations early and promptly initiate the most effective treatments, she explains. Given the poor prognosis associated with 

 V600E mutations, optimizing first-line therapy is important for improving patient outcomes, she reports.

 V600E–mutated mCRC receiving standard chemotherapy, including FOLFIRINOX, achieve a median OS only approximately 14 to 17 months, with limited responses, she adds. Furthermore, in the second-line setting, the use of encorafenib plus cetuximab has yielded a median progression-free survival (PFS) of approximately 4 months and a second-line median OS of approximately 9 months, she states. The introduction of this first-line targeted regimen is promising, as in the pivotal phase 3 BREAKWATER trial (NCT04607421), it delivered an overall response rate of 61% (95% CI, 52%-70%) compared with 40% (95% CI, 31%-49%) with chemotherapy alone, she says. As OS and PFS data continue to mature, this regimen may redefine the standard of care for this population, reinforcing the need for precision medicine approaches in the frontline setting to optimize outcomes, she concludes.

Videos

E. Gabriela Chiorean, MD, FASCO, discusses the FDA approval of encorafenib plus cetuximab and chemotherapy for patients with BRAF V600E–mutated mCRC.

E. Gabriela Chiorean, MD, discusses the recent clinical data with zenocutuzumab in patients with NRG1 fusion–positive pancreatic cancer

Poised Potential With Zenocutuzumab in NRG1+ Pancreatic Cancer

E. Gabriela Chiorean, MD, of Fred Hutch Cancer Center, discusses the recent clinical data with zenocutuzumab in patients with NRG1 fusion–positive pancreatic cancer and the impact the approval of this agent could have on the landscape.


E. Gabriela Chiorean, MD, discusses current standard therapeutics for patients with NRG1 fusion–positive pancreatic cancer. 

Current Standard Therapies for NRG1+ Pancreatic Cancer

E. Gabriela Chiorean, MD, of Fred Hutch Cancer Center, discusses current standard therapeutics for patients with NRG1 fusion–positive pancreatic cancer. 


Standard Treatment Regimens for NRG1+ Pancreatic Cancer

E. Gabriela Chiorean, MD, discusses the benefits and challenges of DNA and RNA testing for NRG1 fusions in patients with pancreatic cancer. 

Choosing RNA or DNA Testing in Pancreatic Cancer

E. Gabriela Chiorean, MD, of Fred Hutch Cancer Center, discusses the benefits and challenges of DNA and RNA testing for NRG1 fusions in patients with pancreatic cancer. 


Choosing RNA Over DNA Testing for NRG1 Fusions in Pancreatic Cancer

E. Gabriella Chiorean, MD, discusses prognosis and rarity of patients with NRG1 fusion–positive pancreatic cancer. 

Prognosis of NRG1+ Pancreatic Cancer

E. Gabriela Chiorean, MD, of Fred Hutch Cancer Center, discusses prognosis and rarity of patients with NRG1 fusion–positive pancreatic cancer. 

Prognosis, Rarity of NRG1+ Pancreatic Cancer

E. Gabriela Chiorean, MD, physician, clinical director, Gastrointestinal Medical Oncology, Seattle Cancer Care Alliance, professor of medicine, University of Washington (UW) School of Medicine, clinical research director, Gastrointestinal Medical Oncology, UW Medicine, professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the role of molecular testing in pancreatic cancer.

Molecular testing of genes, proteins, and RNA sequencing has been a significant advance in the management of pancreatic cancer, Chiorean says. Moreover, the National Comprehensive Cancer Network guidelines indicate that all patients diagnosed with pancreatic cancer, as well as first-degree relatives of diagnosed individuals, should undergo germline genetic testing regardless of disease stage. Additionally, patients with locally advanced, unresectable, or metastatic pancreatic cancer should undergo somatic testing via tumor biopsy or liquid biopsy if tumor testing is unavailable, Chiorean says.

Approximately 10% to 20% of patients with pancreatic cancer harbor a molecular alteration that could inform treatment decisions and provide insight into their prognosis, Chiorean says. Opening the door to additional treatment options can optimize survival for this patient population, Chiorean concludes. 

E. Gabriela Chiorean, MD, discusses the role of molecular testing in pancreatic cancer.  



E. Gabriela Chiorean, MD, FASCO

Articles

Dr Chiorean on Encorafenib Plus Cetuximab for BRAF V600E–Mutated mCRC

Poised Potential With Zenocutuzumab in NRG1+ Pancreatic Cancer

Standard Treatment Regimens for NRG1+ Pancreatic Cancer

Choosing RNA Over DNA Testing for NRG1 Fusions in Pancreatic Cancer

Prognosis, Rarity of NRG1+ Pancreatic Cancer

Dr. Chiorean on the Role of Molecular Testing in Pancreatic Cancer