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J. Backes Floor, MD
Lenvatinib (Lenvima) in combination with paclitaxel-induced weekly activity in patients with recurrent cancer of epithelial epithelial epithelium-resistant endometrium and platinum, resulting in a response rate overall 65%, according to the results of a Phase I study presented at the 50th Annual SGO Meeting held March 16-19 in Honolulu, Hawaii.
In addition, the observed activity was favorable compared to the responses observed in other studies with weekly paclitaxel.
Lenvatinib is a multi-target tyrosine kinase inhibitor currently approved by the FDA for the treatment of recurrent or metastatic thyroid cancer, advanced renal cell carcinoma and hepatocellular carcinoma. Previously, lenvatinib had been studied in recurrent endometrial cancer (ORR, 14% to 22%), while weekly paclitaxel was evaluated in combination with a VEGF inhibitor for the treatment of recurrent cancer of the patient. Ovarian (ORR, 27% to 53%) and recurrent. endometrial cancer (ORR, 20% to 28%).
"It's interesting to see that, if we look at other platinum-resistant ovarian cancer studies, when paclitaxel is combined weekly with other antiangiogenic agents, the response rates median were approximately 30% and median progression-free survival was 6% to 10%. . Moreover, in endometrial cancer, combined with a single-agent anti-angiogenic agent, response rates have been high, but progression-free survival is relatively low, "said Floor J. Backes, MD, Associate Professor in the Department of Obstetrics and Gynecology at the College of Medicine Comprehensive Oncology Center at Ohio State University.
In the single-site study, the researchers hypothesized that paclitaxel and lenvatinib would be safe and effective in patients with recurrent or recurrent endometrial cancer. of a platinum-resistant ovarian cancer. Their main objective in the study was to determine the recommended dose of the Phase II combination. Secondary objectives included safety and tolerability, objective antitumor activity, PHC and the pharmacokinetics of the regimen.
Eligibility criteria included recurrent platinum-resistant ovarian cancer or recurrent endometrial cancer (all histologies); prior unrestricted treatments, with at least one platinum-based pretreatment; measurable disease; and an adequate function of the organs. Previous weekly taxanes and bevacizumab (Avastin) were allowed. Patients had a median age of 63 years (range 45-74 years), the majority were Caucasian (n = 23 years) and had a median of 3 previous treatment lines (range 1-5).
On a 3 + 3 model, 26 patients, including 19 with ovarian cancer (13 serous high grade, 2 low grade serosa, 2 clear cells, 1 endometrial and 1 1 carcinosarcoma) and 7 endometrial cancer (4 endometrial and 3 serum)), were recruited to receive 80 mg / m2 weekly paclitaxel on days 1, 8 and 15; and lenvatinib orally every 28 days.
The doses of lenvatinib were 8 mg (LD1, n = 4), 12 mg (DL2, n = 3), 16 mg (LD3, n = 7) and 20 mg (DL4, n = 6). After determining the maximum tolerated dose (MTD), an additional 6 patients were included in the cohort for expansion.
Patients in the DL1 and DL2 cohorts did not exhibit dose-limiting toxicities, while one patient had mucositis in the DL3 group. The researchers noted that the frequent need for dose reduction for grade 3 (hypertension and fatigue) at LD4 led to the setting of the 16 mg dose of lenvatinib with paclitaxel per week.
Of the 23 patients evaluable for the response, the TCO was 65%, of which 1 patient had a complete response (CR, 4%), 14 had a partial response (PR, 61%), 7 (30%) had a stable disease. and 1 (4%) with progressive disease. The overall clinical benefit rate was 96%.
ORR was 71% in ovarian cancer and 50% in endometrial cancer. In patients with ovarian cancer, the median PFS was 14.0 months and 12.8 months for patients with endometrial cancer.
The median duration of response in patients with CR or RA was 10.9 months. Seven patients continue treatment at the study. The overall median PFS was 14.0 months (95% CI, 5.1 – not achieved) and 54% of patients had PFS for more than 6 months.
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 AEs were hypertension (19%), neutropenia (15%), leukopenia (12%), anemia (12%), lymphopenia (8%), fatigue (8%), diarrhea (8%) and%), vomiting (4%), hematuria (4%), rash (4%), thrombocytopenia (4%) and intestinal perforation (4%).
"This is a small study phase, so we need to confirm these findings in a larger study," said Backes. "We also started thinking about evaluating additional combinations," such as weekly paclitaxel and lenvatinib in combination with pembrolizumab (Keytruda).
Backes FJ, Wei L, DE Cohn, et al. Phase I badessment of lenvatinib and weekly paclitaxel in patients with recurrent endometrial cancer, ovarian, fallopian tube or primary peritoneum. Presented at: 2019 SGO Annual Meeting. March 16-19, 2019; Honolulu, HI. Abstract LBA5.
<<< 2018 SGO Annual Meeting
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