Pembrolizumab plus lenvatinib in women with advanced or recurrent uterine carcinosarcoma.

e17625 Background: Uterine carcinosarcoma (UCS) though rare, accounting for 5% of all uterine cancers, is responsible for more than 16% of all deaths caused by a uterine malignancy. Prognosis remains dismal without significant improvement in survival or recurrence rates in the past 3 decades. Several clinical trials have demonstrated the efficacy of immune checkpoint inhibitors in combination with chemotherapy as first-line therapy in patients with primary advanced or recurrent endometrial cancer. However, UCS has been underrepresented due to its rarity. Methods: A single-institution database was queried for women with advanced or recurrent UCS who received concurrent pembrolizumab and lenvatinib. Patient demographic, oncologic, and immunotherapy outcomes data were recorded. Univariate analysis summarized progression-free survival (PFS) and overall survival (OS). Results: Eleven patients with advanced or recurrent UCS were treated with combination of pembrolizumab and Lenvatinib. The median age at initial diagnosis and initiation of immunotherapy were 63.6 years (IQR 59.6, 65.4) and 65.4 years (IQR, 61.6,67.4), respectively. The majority of patients underwent cytoreductive surgeries (n=10, 90.9%), and had stage III or IV disease (n = 9, 81.8%). All eleven patients had received one to two lines of prior treatment (n = 11, 100%) including a taxane-platinum doublet chemotherapy at initial diagnosis. Three patients had previously received dostarlimab in addition to chemotherapy in upfront or recurrent settings. The majority were MMR proficient (n = 10, 90.9%). A total of 85 doses of pembrolizumab were administered to eleven patients. Starting lenvatinib dose ranged from 10-14mg, with a mean dose of 13.1mg/day. Three patients required dose reduction for treatment related AEs with a final mean dose of 11.8mg/day. Two dose reductions were attributable to grade 3 enterocolitis, the other to intractable hypertension. Two treatments discontinued due to grade 3 AEs requiring steroids use. The median follow-up duration for the cohort was 5.0 months (IQR 2.5, 29.0 months). The median PFS was 4.0 months (95% CI, 3.0-6.0 months), and the median OS was 5.1 months (95% CI, 3.3-5.9 months). The objective response rate was 27.3%. All 3 patients with complete responses had locoregional recurrence with disease confined to the pelvis. Conclusions: UCS is a rare and aggressive type of endometrial cancer characterized by significant heterogeneity in its histopathology, molecular profiling, and treatment approaches. This retrospective case series demonstrates activity of pembrolizumab and lenvatinib combination therapy as a second-line or later-line treatment for recurrent or advanced UCS with some complete responders. Side effects were manageable. These findings warrant further investigation using a prospective trial design to assess the efficacy of this regimen in women with advanced or recurrent UCS.