Impressive response to dual BRAF + MEK inhibition in 2 patients with BRAF mutant cholangiocarcinoma
- 3 years ago
J Gastrointest Oncol. 2016 Dec; 7(6): E98–E102.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177579/
Case 1
A 49-year-old female presented with abdominal bloating and increasing discomfort in June 2014. She was evaluated by imaging and was found to have a large left lobe liver tumor. Fine needle aspiration cytology (FNAC) was consistent with adenocarcinoma. Her CA19-9 (carbohydrate antigen 19.9) and carcinoembryonic antigen (CEA) serum tumor markers and liver function tests were unremarkable. A [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan showed a left lobe liver mass with no evidence of extra hepatic disease. Colonoscopy was unremarkable. She underwent a left hepatectomy with dissection of celiac nodes and cystic duct in July 2014. Post operative histopathological examination revealed a 7.3-cm moderately differentiated ICC, with direct tumor invasion to local adjacent extra hepatic structures, perineural invasion, and with 3 out of 4 positive lymph nodes (Tumor Node Metastasis stage pT3N1—Stage IVA). No loss of mismatch repair protein (MMR) expression was noted by immunohistochemistry. In view of her high risk of disease recurrence, she received five 3-week cycles of gemcitabine and cisplatin adjuvant chemotherapy. Repeat imaging after cycle 5 (4 months) revealed a new 1 cm right liver lobe lesion with new periportal and portacaval nodes and a pericardial lymph node enlargement. She underwent radiofrequency ablation (RFA) to the liver lesion and was switched to second line single-agent capecitabine. Repeat computerized tomography (CT) scan following 3 cycles of capecitabine (2 months) revealed new liver lesions and progressive lymph node enlargement in the pericardial region (Figure 1A,B). Foundation One comprehensive genomic analysis was performed on her original resection specimen and confirmed a BRAF V600E mutation. She was started on dabrafenib 150 mg PO BID (twice a day) and trametinib 2 mg PO QD (once a day) in May 2015. Follow-up imaging studies confirmed a partial response after 6 weeks of treatment and a complete clinical response after 5 months of treatment (RECIST 1.1) (Figure 1C,D). At 9 months of treatment, CT imaging confirmed recurrence of disease in the pericardial node and periportal/portacaval lymph nodes and new right pleural disease. Treatment with dabrafenib and trametinib was discontinued.
Case 2
A 71-year-old lady presented with vague right sided abdominal discomfort of 3 to 4 months duration with associated anorexia and weight loss in August 2015. Her past medical history was significant for cardiac dysrythmia requiring pacemaker placement and mild chronic obstructive pulmonary disease (COPD). CT scan of the abdomen and pelvis showed a 7.8 cm infiltrative mass in the left lobe of liver and other too numerous to count smaller metastases in both lobes of liver (August 2015, Figure 2A). CA19.9 levels was elevated at 84,000 U/mL. Her liver enzymes and other biochemical parameters were unremarka
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177579/
Case 1
A 49-year-old female presented with abdominal bloating and increasing discomfort in June 2014. She was evaluated by imaging and was found to have a large left lobe liver tumor. Fine needle aspiration cytology (FNAC) was consistent with adenocarcinoma. Her CA19-9 (carbohydrate antigen 19.9) and carcinoembryonic antigen (CEA) serum tumor markers and liver function tests were unremarkable. A [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan showed a left lobe liver mass with no evidence of extra hepatic disease. Colonoscopy was unremarkable. She underwent a left hepatectomy with dissection of celiac nodes and cystic duct in July 2014. Post operative histopathological examination revealed a 7.3-cm moderately differentiated ICC, with direct tumor invasion to local adjacent extra hepatic structures, perineural invasion, and with 3 out of 4 positive lymph nodes (Tumor Node Metastasis stage pT3N1—Stage IVA). No loss of mismatch repair protein (MMR) expression was noted by immunohistochemistry. In view of her high risk of disease recurrence, she received five 3-week cycles of gemcitabine and cisplatin adjuvant chemotherapy. Repeat imaging after cycle 5 (4 months) revealed a new 1 cm right liver lobe lesion with new periportal and portacaval nodes and a pericardial lymph node enlargement. She underwent radiofrequency ablation (RFA) to the liver lesion and was switched to second line single-agent capecitabine. Repeat computerized tomography (CT) scan following 3 cycles of capecitabine (2 months) revealed new liver lesions and progressive lymph node enlargement in the pericardial region (Figure 1A,B). Foundation One comprehensive genomic analysis was performed on her original resection specimen and confirmed a BRAF V600E mutation. She was started on dabrafenib 150 mg PO BID (twice a day) and trametinib 2 mg PO QD (once a day) in May 2015. Follow-up imaging studies confirmed a partial response after 6 weeks of treatment and a complete clinical response after 5 months of treatment (RECIST 1.1) (Figure 1C,D). At 9 months of treatment, CT imaging confirmed recurrence of disease in the pericardial node and periportal/portacaval lymph nodes and new right pleural disease. Treatment with dabrafenib and trametinib was discontinued.
Case 2
A 71-year-old lady presented with vague right sided abdominal discomfort of 3 to 4 months duration with associated anorexia and weight loss in August 2015. Her past medical history was significant for cardiac dysrythmia requiring pacemaker placement and mild chronic obstructive pulmonary disease (COPD). CT scan of the abdomen and pelvis showed a 7.8 cm infiltrative mass in the left lobe of liver and other too numerous to count smaller metastases in both lobes of liver (August 2015, Figure 2A). CA19.9 levels was elevated at 84,000 U/mL. Her liver enzymes and other biochemical parameters were unremarka