Weekly Paclitaxel, Lenvatinib, and Pembro in Gynecologic Cancers

Combining weekly paclitaxel/lenvatinib, weekly paclitaxel/pembrolizumab, and lenvatinib/pembrolizumab has shown promise in recurrent ovarian and endometrial cancer, (OC and EC) yet the triplet regimen remains unexplored.

Floor J. Backes and the team aimed to assess the efficacy and toxicity profile of this novel combination in patients with recurrent endometrial or platinum-resistant epithelial OC.

Researchers performed an inclusive analysis of a multi-site investigator-initiated study (NCT04781088; IND153033) involving patients with recurrent EC or recurrent platinum-resistant/refractory OC who had received at least 1 prior line of platinum.

Beginning with a safety lead-in, patients received weekly paclitaxel 60-80 mg/m² IV on days 1, 8, and 15, pembrolizumab 200 mg IV on day 1, and oral lenvatinib 16 mg daily on a 21-day cycle. Toxicities were recorded using CTCAE v5, and response was assessed with imaging after cycle 2, then every 3rd cycle, using RECIST 1.1 criteria.

About 35 patients were enrolled in the study, with 24 (69%) having OC and 11 (31%) having EC. The median age was 64 (range: 37-78), with 17% identifying as Asian, Black, or Mixed race, and 2 as Hispanic.

Most patients had high-grade serous carcinoma (21 patients) 4 endometrioid, 4 clear cell, 4 carcinosarcoma, 1 mixed, and 1 dedifferentiated carcinoma, 89% high grade, and a median of 2 prior lines of therapy (1-3). Approximately 9 patients underwent the safety lead-in, with dose-limiting toxicities observed in 2 out of 4 patients on dose level (DL) 1. The recommended phase 2 dose (RP2D) was confirmed at paclitaxel 60 mg/m².

Among the evaluable 28 patients, 2 had a complete response (6%), 13 (37%) a partial response (37%), and 11 (31%) had stable disease, 2 (6%) progressive disease, and 7 were not evaluable or not assessed yet. The objective response rate (ORR) was 15/35 (43%), 47% in OC and 36% in EC; and 15/28 (54%) in evaluable patients. Median progression free survival (PFS) is 5.8 months (95%CI: 4.4,8.2). Median PFS and duration of response (DOR) in EC were 7.3 and 8.9 months, respectively, compared to 4.6 and 4.2 months in ovarian cancer. Overall survival was 10.3 months (95%CI: 7.3,14.2). Ten patients remain on treatment.

The most common toxicities included (all grades) were Anemia (81%, Leukopenia (84%), Lymphopenia (72%), Fatigue (72%), Hypertension (66%), Diarrhea (63%), Mucositis (63%), Nausea (59%), Hypothyroidism (59%), Anorexia (59%), Proteinuria (56%), Rash (56%), Weight loss (44%). Grade ≥3 toxicities included Hypertension (28%), Neutropenia (25%), Anemia (19%), Rash (19%), Leukopenia (16%), Lymphopenia (16%), Fatigue (16%), Diarrhea (13%), Proteinuria (9%), Mucositis (6%). 11/35 (31%) discontinued treatment for toxicity or patient preference (5) and 14 patients for progression.

The study concluded that weekly paclitaxel/lenvatinib/pembrolizumab demonstrated promising activity in both recurrent endometrial and ovarian cancer, with favorable response rates (ORR 43%) and clinical benefit rates (74%). Despite manageable side effects, a significant number of patients discontinued treatment due to toxicity or patient preference. Nonetheless, this regimen may offer a valuable treatment option for these challenging cancers.

The trial was sponsored by Floor Backes, MD from The Ohio State University.

Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=474139&CONF=AM2024&CKEY=

Clinical Trial: https://clinicaltrials.gov/study/NCT04781088

Backes F.J., Bixel K.L., Nagel C.I., et al. (2024). “A phase II study of weekly paclitaxel, lenvatinib, and pembrolizumab among patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal cancer.” Presented at SGO 2024.