HONOLULU – The combination of lenvatinib and paclitaxel was considered active and well tolerated in a phase 1 trial of patients with recurrent endometrial or ovarian cancer.
Daily lenvatinib plus weekly paclitaxel produced an objective response rate of 65% and a clinical benefit rate of 96%.
Most adverse events (AEs) were grade 1 to 2. The most common grade 3 or higher AEs were hypertension, cytopenias, fatigue, and diarrhea.
, of the Ohio State University Comprehensive Cancer Center in Columbus presented these results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
The trial () included 26 patients with a median age of 63 years (range, 45-74). All patients had adequate organ function and measurable disease.
Nineteen patients had ovarian cancer: 13 with high-grade serous, 2 with low-grade serous, 2 clear cell, 1 endometrioid, and 1 carcinosarcoma. Seven patients had endometrial cancer: 4 endometrioid and 3 serous.
The patients must have received at least one prior platinum-based therapy. In all, they had a median of 3 prior therapies (range, 1-5).
The patients received intravenous paclitaxel at 80 mg/m2 on days 1, 8, and 15 of a 28-day cycle. They also received oral lenvatinib daily at doses of 8 mg (n = 4), 12 mg (n = 3), 16 mg (n = 13), or 20 mg (n = 6).
There were no dose-limiting toxicities (DLTs) in the 8-mg or 12-mg dose groups. There was one DLT (mucositis) at the 16-mg dose level, and two DLTs (hypertension and fatigue) occurred at the 20-mg dose level.
“[At 20 mg,] patients were unable to take more than 75% of the study drug during the first cycle, and that was considered a DLT,” Dr. Backes said. “So our recommended phase 2 dose was lenvatinib 16 mg daily and paclitaxel 80 mg.”
“Toxicities were fairly common,” Dr. Backes noted. “The majority of these were cytopenias, but we also saw some GI toxicity – mucositis, diarrhea, nausea – and the VEGF inhibitor–related toxicities that we’re familiar with – hypertension, proteinuria, epistaxis. Fortunately, the majority of toxicities were grade 1 to 2.”
The most common AEs of any grade were leukopenia (58%), anemia (50%), mucositis (46%), diarrhea (46%), lymphopenia (42%), anorexia (42%), hypertension (42%), fatigue (42%), nausea (35%), proteinuria (27%), epistaxis (27%), and hoarseness (27%).
Grade 3 or higher AEs included hypertension (19%), neutropenia (15%), leukopenia (12%), anemia (12%), lymphopenia (8%), fatigue (8%), diarrhea (8%), mucositis (4%), vomiting (4%), hematuria (4%), rash (4%), and thrombocytopenia (4%).
“There was one patient [4%] who had a bowel perforation – small bowel perforation – at the site of previous stenosis after multiple prior bowel surgeries,” Dr. Backes noted.
In the 23 evaluable patients, the objective response rate was 65%, and the clinical benefit rate was 96%. One patient had a complete response, 14 had partial responses, 7 had stable disease, and 1 progressed.
The median duration of response was 10.9 months, and the median progression-free survival was 14.0 months.
The objective response rate was 71% in patients with ovarian cancer and 50% in patients with endometrial cancer. The median progression-free survival in these groups was 14.0 months and 12.8 months, respectively.
Dr. Backes said these results suggest lenvatinib plus paclitaxel is safe and active in recurrent ovarian and endometrial cancer, but these findings must be confirmed in a larger study.
This was an investigator-initiated study supported by Eisai. Dr. Backes disclosed relationships with Eisai, ImmunoGen, Clovis Oncology, Tesaro, Merck, and Agenus.
SOURCE: Backes FJ et al. SGO 2019, .