anlotinib + pembrolizumab

The combination of anlotinib and pembrolizumab represents a promising therapeutic approach that combines anti-angiogenic therapy with immune checkpoint inhibition. This combination has shown efficacy in various cancer types, particularly in non-small cell lung cancer (NSCLC) and other advanced solid tumors. ## Mechanism of Action Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) that inhibits tumor angiogenesis and growth by targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and c-Kit[1][6]. Pembrolizumab is a highly selective monoclonal antibody targeting PD-1, which has been approved for treating advanced malignant melanoma and NSCLC[1]. The combination works synergistically - anlotinib can normalize tumor vasculature and facilitate the entry of tumor-infiltrating lymphocytes, which are reactivated by pembrolizumab, allowing them to penetrate deeper into the tumor mass and better target malignant cells[1]. ## Clinical Evidence Several studies have demonstrated the efficacy of this combination: 1. In patients with advanced NSCLC, the combination showed good response and prolonged partial response compared to pembrolizumab monotherapy[5][7]. 2. For refractory or recurrent High-Grade Serous Ovarian Cancer, the anlotinib-pembrolizumab combination showed promising efficacy with progression-free survival of 13.0 months compared to 8.0 months with pembrolizumab monotherapy[2]. 3. In EGFR-mutant NSCLC patients who had failed on EGFR-TKI and platinum-based chemotherapy, the combination resulted in significantly longer progression-free survival (3.24 months vs 1.5 months), overall survival (15.97 months vs 7.41 months), and objective response rate (21.4% vs 3.1%) compared to pembrolizumab alone[7]. 4. The combination has also shown efficacy in rare cancers such as pulmonary sarcomatoid carcinoma[1] and low-grade myofibroblastic sarcoma of the pancreas[6]. ## Safety Profile The combination therapy has demonstrated a favorable safety profile. In the study of patients with High-Grade Serous Ovarian Cancer, Grade 3 treatment-related adverse events were recorded in 20% of participants receiving the combination treatment, comparable to the 16.7% in the pembrolizumab monotherapy group[2]. This combination represents an innovative approach to cancer treatment by simultaneously targeting tumor angiogenesis and enhancing anti-tumor immune responses.