Abstract 774P
Background
Antiangiogenic therapy plus immune checkpoint inhibitors have become a promising strategy for advanced cervical cancer (CC). This phase II study aims to evaluate the efficacy and safety of anlotinib (a novel multi-target TKI, inhibiting tumour angiogenesis and proliferative signalling) plus sintilimab (an antibody against PD-1) in pts with advanced CC.
Methods
Pts who have received at least once platinum-based chemotherapy, recurrent advanced cervical cancer, PD-L1 for CPS>1, ECOG 0-1 were considered eligible for enrollment . Anlotinib was taken orally (10mg, qd, d1-14, 21 days per cycle), and sintilimab was administered intravenously (200mg, q3w). The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS), safety and biomarkers.
Results
Between September 2019 and April 2021, 42 pts with a median age of 52 years (IQR:47-58) were enrolled. In the efficacy-evaluable population (n=39), the ORR of 61.5% (24/39, 95% CI:44.9 - 75.9) and the DCR was 94.9% (37/39, 95% CI:80.7 - 98.8). The mPFS was 9.4m (95%CI:8.02-11.63) and the median response time was 1.71m (95%CI:1.38-2.76). Targeted next-generation sequencing was performed using a 520-gene panel (OncoScreen Plus, Burning Rock Biotech) to identify genetic alterations that might be associated with treatment response in 39 pts. Frequently mutated genes included PIK3CA (31%), FAT1 (23%), PRKDC (21%), KMT2D (18%), and TP53 (8%). Our results demonstrated that harboring mutations in PIK3CA alone, other genes related to PI3K-AKT signaling pathway, or KMT2D was associated with significantly better objective response (p<0.05). Conversely, mutations in STK11 was associated with significantly poorer objective response to the combination therapy (p<0.05). The most common adverse events (AEs) were grade 1 or 2. The most common grade 3 AEs were hypertension (4.8%), hyponatremia (4.8%). No higher AEs and treatment-related death were observed.
Conclusions
Anlotinib plus sintilimab showed a promising efficacy with a favorable toxicity profile for pts with advanced CC. We will report more data in the future.
Clinical trial identification
ChiCTR1900023015, 2019/05/07.
Editorial acknowledgement
Legal entity responsible for the study
Q. Xu.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.