A patient with metastatic intrahepatic cholangiocarcinoma (CCA) presenting with a CDKN2A/B loss exhibited a partial response to treatment with the CDK4/6 inhibitor called palbociclib, thus underlining the importance of genetic testing in the context of CCA, according to a recently published case report in OncoTargets and Therapy.
Although radical surgery is the current standard of care for CCA, an important percentage of patients are not candidates for surgery due to the advance of metastatic disease at the moment of diagnosis. The overall survival of patients with metastatic disease receiving first-line therapy with gemcitabine and cisplatin regimen is approximately 11 months.
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Targeted therapies for metastatic CCA have made great progress in the last decade, and there is high interest in discovering biomarkers that could help guide therapy.
The case involved a 68-year-old male admitted due to the incidental finding of a liver mass. His past medical and family history were unremarkable except for hypertension and gout. Further imaging studies through computed tomography (CT) revealed a mixed-density lesion in the left lobe with an unclear boundary with the gallbladder.
The patient underwent drug-eluting-beads transhepatic arterial chemotherapeutic embolism and subsequent surgical resection of the liver tumor, gallbladder, and biliary tract exploration two months later.
Histological examination of the resected specimen led to the diagnosis of stage 2 ICC with no nerve fiber, liver capsule, or satellite nodules. A postoperative CT revealed a new nodule in the s6 segment of the liver, suggestive of intrahepatic metastasis.
Formalin-fixed, paraffin-embedded samples were subjected to targeted next-generation sequencing in order to optimize the treatment strategy. Results revealed a deletion of CDKN2A and CDKN2B genes (CDKN2A/B loss). The attending physicians started the patient on a palbociclib protocol based on previous studies.
Follow-up CT scans showed moderate shrinking of the nodules, and the concentration of tumor markers remained at normal levels during the following months. According to the Response Evaluation Criteria in Solid Tumors version 1.1, the patients exhibited a partial response to treatment.
The patient continued under strict medical vigilance, and 2 years after treatment, imaging studies revealed new nodules, suggesting recurrence. The patient had a 2-year progression-free survival.
“To sum up, this case report described a metastatic ICC patient harboring CDKN2A/B loss responded to palbociclib as the first-line therapy, suggesting that comprehensive genomic variation detection can provide new strategies for individualized treatment of advanced ICC patients,” the authors concluded.
Reference
Fan W, Wang C, Zhong X, et al. A refractory case of CDKN2A/B loss metastatic intrahepatic cholangiocarcinoma achieving a partial response after first-line treatment with palbociclib. OncoTargets Ther. Published online January 17, 2023. doi:10.2147/ott.s390458
