Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer

Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study

“…The combination of lenvatinib with a PD-1 inhibitor has been used in various solid cancers (26,27), including HCC (12,(28)(29)(30), cholangiocarcinoma (31,32), renal cancer (33)(34)(35)(36)(37), endometrial cancer (38)(39)(40)(41), gastric cancer (42,43) and adrenal cortical carcinoma (44). Lenvatinib plus a PD-1 inhibitor appears to be effective in patients with corresponding molecular subtypes regardless of the type of cancer, and the evidence from clinical trials indicates that the effectiveness of this treatment regimen might depend on the molecular subtype rather than the type of cancer.…”

Angiogenesis: A Pivotal Therapeutic Target in the Drug Development of Gynecologic Cancers

“…The primary endpoint of a 24-week ORR was met (38%, 95%CI: 28.8 to 47.8%) and activity was demonstrated regardless of mismatch repair (MMR) status, which is a known marker predictive of response to immunotherapy. A follow-up phase 3 study, KEYNOTE-775, which enrolled 827 women who had progressed after one platinum-based regimen to receive either lenvatinib and pembrolizumab or a physician’s choice of chemotherapy, met its co-primary endpoints of PFS and OS [ 4 , 8 ]. Median PFS was 7.2 vs. 3.8 months (HR 0.56; p < 0.0001) and median OS was 18.3 vs. 11.4 months (HR = 0.63; p < 0.0001).…”

“…In endometrial cancers, it is likely in the future that biomarkers will guide further subclassifications by therapeutic agent; recent publications have explored differential responses between patients across the spectrum of MMR deficiencies with pembrolizumab [ 108 , 109 ]. For those who are less likely to have deep, prolonged responses to immunotherapy, KEYNOTE-775 [ 8 ] suggests that lenvatinib may be more useful in this situation, but this needs to be explored further. Careful dissection of biomarkers in endometrial cancer, such as those differentiating between somatic MMR deficiency and germline MLH1 methylation [ 108 ], may provide interesting results in future trials.…”

“…However, caution with regards to cumulative toxicity, careful patient selection, education and monitoring of knowledge translation for clinical practice needs to be considered. One example of the importance of patient monitoring is the previously discussed KEYNOTE-775 study in advanced-stage endometrial cancer, where lenvatinib and pembrolizumab led to a grade 3 treatment-emergent adverse event (TEAE) rate of 89%, with 14% of patients discontinuing both drugs due to a TEAE [ 4 , 8 ]. Due to the substantial rates of adverse events, oncologist-led directives are trialing lower doses of lenvatinib and finding similar efficacy outcomes, with improved toxicity [ 116 ].…”

“…Cancers 2022, 14, 1122 2 of 22 In addition, other anti-angiogenics have demonstrated modest clinical efficacy in gynecologic cancers, although their role in standard treatment regimens remains unclear. Of these, one of the most widely studied in ovarian cancer is cediranib, an oral multi-targeted tyrosine kinase inhibitor (TKI) that has shown some clinical efficacy in recurrent ovarian cancer as a monotherapy and in combination with other drug classes [5][6][7][8]. Ongoing pre-clinical work and clinical trials will be paramount in discovering novel mechanisms for regulating tumor vascularization and improving survival in patients with gynecologic malignancies.…”