A panel of expert oncologists present the case of a 46-year-old woman with HER2+ metastatic colorectal cancer, who is treated with tucatinib in the second-line setting.
Cathy Eng, MD, FACP, FASCO: Welcome to this Cancer Network®Around the Practice program titled “Treatment Strategies in HER2+ Colorectal Cancer and Expert Case-Based Discussion.” I’m your host, Dr Cathy Eng, a professor and coleader of the Vanderbilt-Ingram Cancer Center, and I’m with the GI [gastrointestinal] cancer research program at Vanderbilt University Medical Center in Nashville, Tennessee. I have a wonderful panel of experts who’ve joined me for this discussion. I’d like to invite my fellow panelists to introduce themselves.
Suneel Kamath, MD: Hi, I’m Dr Suneel Kamath from the Cleveland Clinic Taussig Cancer Center in Cleveland, Ohio.
Michael Foote, MD: Hi, everyone. I’m Mike Foote from Memorial Sloan Kettering Cancer Center in New York, New York, and I’m a GI oncologist.
Arvind Dasari, MD, MS: I’m Arvind Dasari. I’m a medical oncologist from The University of Texas MD Anderson Cancer Center in Houston, Texas.
Aparna Parikh, MD: Hi, I’m Aparna Parikh. I’m from MGH [Massachusetts General Hospital] in Boston, Massachusetts, and I’m also a GI oncologist.
Cathy Eng, MD, FACP, FASCO: Thank you all for joining me. We’re going to discuss key updates that were presented at recent meetings regarding the testing and treatment of metastatic colorectal cancer. We’ll discuss these updates in the context of the treatment landscape and how they might impact clinical practice. Let’s begin.
Suneel Kamath, MD: Let’s start with case 1. This is a 46-year-old woman who presents with left lower quadrant abdominal pain and has difficulty with bowel movements and thin stool caliber. She was found on imaging to have a distal sigmoid colon mass with liver metastases and 3 peritoneal deposits. Colonoscopy revealed a near-obstructing distal sigmoid colon mass and IF2-confirmed adenocarcinoma. She had a diverting loop colostomy and excisional biopsy of the 3 peritoneal nodules, which confirmed metastatic colorectal adenocarcinoma. Tissue-based NGS [next-generation sequencing] testing from a peritoneal nodule showed the tumor was RAS wild type, BRAF wild type, MSS [microsatellite stable], and ERBB2 amplified, which is also confirmed by HER2 [human epidermal growth factor receptor 2] IHC3+ [immunohistochemistry 3+]. You can also see the tumor of his PIK3CA wild type with a TMB [tumor mutational burden] of 5.6 mutations per megabase.
The patient was initially treated with FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan] and bevacizumab [Avastin] for 6 cycles. Because of her young age and high burden of disease, we wanted to go with triplet therapy. She was put on capecitabine [Xeloda] and bevacizumab maintenance therapy for 23 cycles but ultimately experienced a progression of disease in the liver. She had significant residual grade 2 neuropathy due to the prior oxaliplatin. We treated her with FOLFIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan] and bevacizumab for 6 cycles, but she again unfortunately experienced a progression of disease in the liver.
These are her lesions at progression in the livers, and you can see a decent bulk of the liver tumor. At this point, we decided to treat her due to the HER2 positivity with tucatinib [Tukysa] and trastuzumab [Herceptin] as a chemotherapy-free regimen. For someone who’s had quite a bit of prior chemotherapy, it was an attractive option. This was her imaging after just 4 cycles of treatments, and you can see significant regression in all sites of disease in the liver. It was a great response. This shows it was the same before and after. It’s showing a great response after 3 months of therapy.
As the first follow-up, she developed grade 2 diarrhea, which required a 1-week dose interruption of tucatinib, but we were able to resume without dose reduction using scheduled loperamide [Imodium]. With low-grade diarrhea, that’s very manageable. She also has ongoing grade 1 fatigue, rash, and anemia, but she continues to be very active, work full time as an accountant, and lead a very full life.
Cathy Eng, MD, FACP, FASCO: Dr Kamath, you mentioned that your patient was young. Can you briefly discuss the epidemiology data and trends surrounding metastatic colorectal cancer in early onset patients?
Suneel Kamath, MD: Unfortunately, young-onset colorectal cancer is increasingly a problem. This is a relatively common disease—around 150,000 cases per year and 52,000 deaths per year. But increasingly the share of incidents is among the young: 1 in 5 are under age 50. This is very concerning and a trend that we don’t understand all that well. It’s a big area of investigation.
Cathy Eng, MD, FACP, FASCO: Thank you for mentioning that.
Transcript edited for clarity.