Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal Cancer

• Published in: Gynecologic oncology Vol. 162; no. 3; pp. 619 - 625
• Main Authors: Backes, Floor J., Wei, Lai, Chen, Min, Hill, Kasey, Dzwigalski, Kyle, Poi, Ming, Phelps, Mitch, Salani, Ritu, Copeland, Larry J., Fowler, Jeffrey M., Cohn, David E., Bixel, Kristin, Cosgrove, Casey, Hays, John, O'Malley, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Carcinoma, Ovarian Epithelial - drug therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Neoplasm; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - metabolism; Fallopian Tube Neoplasms - drug therapy; Fallopian Tube Neoplasms - metabolism; Female; Genital Neoplasms, Female - drug therapy; Genital Neoplasms, Female - metabolism; Humans; Lenvatinib; Middle Aged; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Paclitaxel - pharmacokinetics; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - metabolism; Phase I; Phenylurea Compounds - administration & dosage; Phenylurea Compounds - adverse effects; Phenylurea Compounds - pharmacokinetics; Platinum resistant ovarian cancer; Quinolines - administration & dosage; Quinolines - adverse effects; Quinolines - pharmacokinetics; Recurrent endometrial cancer; Weekly paclitaxel; Recurrent endometrial cancer; Lenvatinib; Weekly paclitaxel; Phase I; Platinum resistant ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2021.06.032

To estimate the maximally tolerated dose (MTD) and describe toxicities associated with lenvatinib and weekly paclitaxel in patients with recurrent endometrial and platinum resistant epithelial ovarian cancer. Using a 3 + 3 design patients were given weekly paclitaxel 80 mg/m2 IV day 1, 8, 15 and oral levantinib daily on a 28-day cycle. Lenvatinib dose levels were 8 mg, 12 mg, 16 mg, 20 mg. Toxicities were recorded using CTCAE v4.03 and response was determined with imaging after cycle 2, then every 3rd cycle, using RECIST 1.1 criteria. 26 patients were enrolled; 19 with ovarian cancer (14 high grade serous, 1 low grade serous, 2 clear cell, 1 endometrioid, and 1 carcinosarcoma), and 7 with endometrial cancer (3 serous, and 4 endometrioid). The MTD was established at lenvatinib 16 mg and weekly paclitaxel 80 mg/m2. Toxicities (all grades) occurring in ≥25% of patients included anemia, neutropenia, lymphopenia, mucositis, nausea, diarrhea, anorexia, hypertension, fatigue, proteinuria, epistaxis, hoarseness. Twenty-three patients were evaluable for response and PFS; 15 (65%) had a partial response, 7 (30%) stable, 1 (4%) progressive disease with an objective response rate of 65%; 71% in ovarian and 50% in endometrial cancer. Median progression free survival (PFS) is 12.4 months; 14.0 months in endometrial cancer, 7.2 months in ovarian cancer; 54% had a PFS > 6 months. The median duration of response for PR patients (n = 15) was 10.9 months. The regimen was tolerable with manageable side effects. Encouraging activity was observed in endometrial and ovarian cancer, and warrants further development. •Weekly paclitaxel with lenvatinib shows encouraging activity in multiple, rare and difficulty to treat, histologic subtypes.•This regimen provides a new active option for patients with recurrent platinum resistant ovarian or endometrial cancer.•The combination is safe and side effects are manageable.•This regimen is also reasonable for patients who are not candidates for lenvatinib/pembrolizumab or other immunotherapy.