Tumor lenvatinib addiction and withdrawal rebound response in patients with advanced endometrial cancer Journal Article
| Authors: | Lam, C.; Sarasohn, D.; Weigelt, B.; Zamarin, D. |
| Article Title: | Tumor lenvatinib addiction and withdrawal rebound response in patients with advanced endometrial cancer |
| Abstract: | Combination therapy of lenvatinib, a multitargeted tyrosine kinase inhibitor (TKI), plus pembrolizumab, a monoclonal antibody targeting programmed death receptor 1 (PD-1), was recently approved by the Food and Drug Administration for therapy of advanced endometrial cancer. This case series highlights three patients with endometrial serous carcinoma who experienced disease stabilization or slow progression on lenvatinib plus pembrolizumab followed by rapid symptomatic growth of disease after lenvatinib discontinuation, and subsequent repeated response and symptom resolution after lenvatinib re-initiation. All patients died of disease complications 3 to 10 months after retreatment with lenvatinib. These observations highlight an important phenomenon of lenvatinib withdrawal rebound, likely driven by oncogenic signaling pathways upregulated in response to lenvatinib therapy. The findings of this case series represent a potential area for further research into the underlying mechanism for rebound and repeated response to lenvatinib, as well as strategies to mitigate disease flare related to lenvatinib withdrawal. © 2023 The Author(s) |
| Keywords: | immunohistochemistry; signal transduction; adult; clinical article; human tissue; treatment response; aged; middle aged; constipation; case report; postoperative period; advanced cancer; ascites; cancer combination chemotherapy; cancer growth; drug withdrawal; treatment duration; paclitaxel; nuclear magnetic resonance imaging; endometrial cancer; endometrium carcinoma; lymph node dissection; endometrium cancer; cytoreductive surgery; carboplatin; low drug dose; computer assisted tomography; multiple cycle treatment; epidermal growth factor receptor 2; protein p53; abdominal pain; liver metastasis; lung metastasis; intestine perforation; ca 125 antigen; carcinomatous peritonitis; trastuzumab; hand foot syndrome; disease exacerbation; abdominal hysterectomy; lymph node biopsy; lymphadenopathy; retreatment; hysteroscopy; spine metastasis; endometrium biopsy; dilatation and curettage; hospice care; abdominal distension; lung nodule; transvaginal echography; international federation of gynecology and obstetrics; paracentesis; acute abdomen; endometrium polyp; acute cholecystitis; laparoscopic hysterectomy; influenza a; lymph vessel metastasis; disease burden; lenvatinib; human; female; article; pembrolizumab; vaginal brachytherapy; cholecystostomy; postmenopause bleeding; bilateral salpingo-oophorectomy; lenvatinib addiction; rebound response; bacterial peritonitis |
| Journal Title: | Gynecologic Oncology Reports |
| Volume: | 49 |
| ISSN: | 2352-5789 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2023-09-30 |
| Start Page: | 101258 |
| Language: | English |
| DOI: | 10.1016/j.gore.2023.101258 |
| PROVIDER: | scopus |
| PMCID: | PMC10448068 |
| PUBMED: | 37636495 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Dmitriy Zamarin -- Source: Scopus |
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