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Significant Response to Palbociclib Plus Lenvatinib as Second-line Treatment for CDKN2A/2B Deletion Intrahepatic
Kai Liu1,2, Ziyue Huang2, Lijin Zhao1
1Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Abstract:
Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.
Insights
A biliary tract cancer patient with a CDKN2A/2B deletion showed tumor regression with palbociclib and lenvatinib. This chemotherapy-free regimen offers a promising second-line treatment option for this specific genetic alteration.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Biliary tract cancer (BTC) often presents with advanced disease, and treatment options for specific genetic alterations like Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions remain limited.
- Intrahepatic cholangiocarcinoma (ICC) is a subtype of BTC where CDKN2A/2B deletions are observed, necessitating novel therapeutic strategies.
Observation:
- A 64-year-old female with intrahepatic cholangiocarcinoma and lymph node metastasis experienced disease recurrence after surgery and adjuvant chemotherapy.
- Genetic analysis revealed a CDKN2A/2B deletion, suggesting sensitivity to palbociclib.
- The patient received a combination of palbociclib and lenvatinib, alongside radiotherapy for an intracranial lesion.
Findings:
- The patient achieved significant regression of pulmonary metastasis and complete disappearance of the intracranial tumor after 12 months of treatment.
- Progression-free survival was 32.2 months and overall survival was 34.4 months.
- Disease progression occurred at 32.2 months, characterized by adrenal gland metastasis enlargement and new lung metastasis.
Implications:
- This case highlights the potential of palbociclib plus lenvatinib as an effective chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma harboring CDKN2A/2B deletions.
- Targeted therapy combined with radiotherapy may improve outcomes in patients with advanced BTC and specific genetic vulnerabilities.
- Further clinical trials are warranted to validate these findings in a larger patient cohort.
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