PracticeUpdate Oncology May 2019

SGO 2019 27

Lenvatinib +Weekly Paclitaxel Looks Promising for Recurrent Endometrial, Ovarian, Fallopian Tube and Primary Peritoneal Cancer Activity was seen in both endometrial and ovarian cancer. L envatinib + weekly paclitaxel has been shown to yield favorable responses and warrants further development,

and then every third cycle, using Response Evaluation Criteria in Solid Tumors v1.1. Overall, this study included 26 patients (n=19 ovarian cancer, including one with carcinosarcoma; n=7 endometrial cancer, including 3 serous and 3 endometrioid). A total of 6 patients completed the 20 mg lenvatinib dose (maximally tolerated dose of lenvatinib 20 mg with weekly paclitaxel 80 mg/m 2 ). Toxicities (all grades) occurring in ≥25% of patients included leukopenia, anemia, neutropenia, leukopenia, lymphopenia, mucositis, nausea, diarrhea, anorexia, hypertension, fatigue, nausea, proteinuria, epistaxis, and hoarseness. Grade ≥3 toxicities were hypertension (19%), neutropenia (15%), leukopenia (12%), ane- mia (12%), lymphopenia (8%), fatigue (8%), diarrhea (8%), mucositis (4%), vomiting (4%), hematuria (4%), rash (4%) and thrombocy- topenia (4%). In all, 23 patients are evaluable for response. One experienced a complete response (4%); 14 (61%), partial response; 7 (30%), stable disease; and one (4%), pro- gressive disease. The objective response rate was 12/19 (65%) in ovarian cancer and 3 of 6 (50%) in endo- metrial cancer. Median progression-free survival was 14.0 months (95% confidence interval 5.1 – not reached). Overall, 54% experienced progression-free survival >6 months. Dr. Backes explained that lenvatinib is an oral tyrosine kinase inhibitor of vas- cular endothelial growth factor receptors 1–3, fibroblast growth factor receptors 1–4, platelet-derived growth factor receptor-β, RET, and KIT. Lenvatinib was approved in 2015 for locally recurrent or metastatic, progressive, radi- oactive iodine-refractory differentiated thyroid cancer; in combination with everoli- mus for advanced renal cell carcinoma in 2016; and in 2018 for unresectable hepa- tocellular carcinoma. Dr. Backes concluded that the maximally tolerated dose of lenvatinib + weekly paclitaxel was found to cause managea- ble side effects. Activity was seen in both endometrial and ovarian cancer (objective

the outcome of a phase I evaluation reports. Floor J. Backes, MD, of the Ohio State University, James Cancer Hospital in Columbus, and colleagues set out to esti- mate the maximally tolerated dose and describe toxicities associated with lenvati- nib and weekly paclitaxel in patients with recurrent endometrial and platinum-resist- ant epithelial ovarian cancer. Using a 3+3 design, patients were given weekly paclitaxel 80 mg/m 2 IV on days 1, 8, and 15 + oral lenvatinib daily on a 28-day cycle. Lenvatinib dose levels were 8, 12, 16 and 20 mg. After determining the maximally tolerated dose, 6 additional patients were enrolled to the expansion cohort. Toxicities were recorded using Common Terminology Cri- teria for Adverse Events v4.03. Response was determined with imaging after cycle 2 progression-free survival (11.3 months in the dendritic cell immunotherapy group and 10.1 months in the chemotherapy group; hazard ratio 0.77, 95% confidence interval 0.44–1.35, difference not significant). On the contrary, survival curves showed a significant difference in favor of dendritic cell immunotherapywith chemotherapy (HR0.38, 95%CI 0.20–0.74, P = .0032), corresponding to 2-year survival of 72.4% and 40.9% in the dendritic cell immunotherapy and chemo- therapy groups, respectively (difference 31.5%, 95% CI 5.3–57.7%). Median overall survival reached 35.5 months in the dendritic cell immunotherapy group and 22.1 months in the chemother- apy group. Dr. Cibula concluded that the addition of den- dritic cell immunotherapy to chemotherapy was shown to prolong overall survival signif- icantly. He hypothesized that the effect on overall but not progression-free survival was due to the induction of long-lasting antitumor immunity by dendritic cell immunotherapy. A larger, phase III clinical trial is planned for 2019. www.practiceupdate.com/c/80899

response rate, 65%; and clinical benefit rate, 96%). Response was favorable compared with that seen in other studies with weekly pacl- itaxel (objective response rate 20% to 28%). Lenvatinib warrants further development in recurrent endometrial, ovarian, fallo- pian tube, and primary peritoneal cancer. The drug was granted the breakthrough therapy designation in combination with pembrolizumab for advanced and/or meta- static non-microsatellite instability high/ proficient mismatch repair endometrial carcinoma that has progressed after at least one prior systemic therapy. The designation will expedite the devel- opment and review of the combination in this setting. The designation was based on interim data from the phase Ib/II basket study 111/KEYNOTE-146 trial, reported at the 2018 annual meeting of the American Soci- ety of Clinical Oncology (ASCO). In the 53-patient endometrial cancer cohort, the objective response rate at week 24 was 45.3% (95% CI 31.6–59.6). The overall objective response rate was 47.2% (n=25; 95% CI 33.3–61.4), including three com- plete responses and 25 partial responses. Breakthrough status was the second such designation for the lenvatinib + pembroli- zumab combination, which holds promise in 11 types of cancer. www.practiceupdate.com/c/81358

VOL. 3 • NO. 2 • 2019