Long-Term Efficacy and Safety of Anlotinib as a Monotherapy and Combined Therapy for Advanced Sarcoma

Abstract

Objective To analyze the effectiveness of the long-term (> 12 months) administration of anlotinib as a monotherapy or combined therapy in patients with advanced sarcomas. Methods A retrospective analysis was conducted of patients with advanced sarcomas with measurable target lesions since 2018. Twenty-two of the patients had taken anlotinib regularly for > 12 months. The patients’ general information and the drug’s clinical efficacy and toxicity data were collected and statistically analyzed using RECIST 1.1 to measure the target lesions and tumor PFS time as the main endpoints. We used a swimmer plot to observe the drug’s efficacy and duration, and employed a waterfall plot to express the best treatment effect. Results The study included 14 male and 8 female patients, ranging in age from 14 to 75 (mean: 44.82) years. The primary diseases included alveolar soft part sarcoma, synovial sarcoma, leiomyosarcoma, and others. The metastasis sites were the lungs in fifteen cases, lymph nodes in four cases, and multiple sites in three cases. Fourteen patients had previously undergone chemotherapy. The current therapy protocol was oral anlotinib alone for nine cases, combination chemotherapy for nine cases, and combination immunotherapy (anti-PD-1) for four cases. The highest clinical efficacy was complete remission (CR) in four (18.18%) cases, partial response (PR) in five (22.73%) cases, and stable disease in 13 (59.09%) cases, with an odds ratio of response of 40.91%. The mean PFS for the CR, PR, and stable disease groups was 16.50, 14.50, and 29.31 months, respectively (p < 0.05). The main adverse effects included hand-foot syndrome, hypertension, and leukopenia. Conclusion Anlotinib monotherapy or combination therapy can be more effective and safer for certain advanced sarcomas, with more extended maintenance and acceptable side effects. Clinical efficacy at the CR and PR levels might predict the long-term PFS in certain advanced sarcomas.

Advanced diffuse hepatic angiosarcoma treated successfully with TACE and targeted immunotherapy: A case report

“…Anlotinib, a novel oral multi-targeted receptor TKI, acts on a proven target’s vascular endothelial growth factor (VEGF) isoforms and their receptors (VEGFRs), thereby demonstrating significant antitumor effects through the inhibition of angiogenetic and proliferative signaling. Anlotinib is approximately 20-500 times as potent as comparable TKIs ( 10 , 11 ). Yao et al ( 11 ) reported in 2022 that Anlotinib as a monotherapy or in combination therapy can be more effective and safer for certain advanced sarcomas.…”

“…Anlotinib is approximately 20-500 times as potent as comparable TKIs ( 10 , 11 ). Yao et al ( 11 ) reported in 2022 that Anlotinib as a monotherapy or in combination therapy can be more effective and safer for certain advanced sarcomas. Usually a reduction in the diameter of the target lesion about 1 month after the therapy, but certain disappeared lesions reappear and progress rapidly, a phenomenon that might be related to drug resistance or insufficient antitumor effect.…”

“…Immunotherapy targeting programmed death 1 (PD-1) receptor and its ligand (PD-L1) has recently been found to have activity in multiple cancers ( 9 ). Anlotinib, a novel oral multi-targeted receptor tyrosine kinase inhibitor (TKI), has a broad spectrum of inhibitory action on tumor angiogenesis and growth ( 10 ), and showed positive effects ( 11 ) as a monotherapy and in a combination therapy for advanced sarcoma. To our best knowledge, this case report presents the first case of an advanced diffuse PHA with ruptured hemorrhage that has been effectively treated with TACE and Anlotinib plus Camrelizumab, as well as includes our detailed experience in treating such a rare malignancy.…”

Emerging Trends in Immunotherapy for Adult Sarcomas

“… 43 Another therapy that has shown some benefit in case series is the TKI, anlotinib, in combination with PD-1 inhibitors in ASPS and epithelioid sarcoma. 44 Two patients with ASPS achieved stable disease for 12 months and complete response (CR) in 3 months that maintained for 19 months; the patient with epithelioid sarcoma achieved a CR in 1 month that maintained for 23 months. Most recently, durvalumab/tremelimumab combination therapy displayed activity in advanced or metastatic sarcoma, including STS and osteosarcoma and chordoma, with 49% reaching a 12-week PFS (median follow-up of 37.2 months).…”

Epithelioid sarcoma

“…Another therapy that has shown some benefit in case series is another TKI, anlotinib, in combination with PD-1 inhibitors [72]. Some data on dasatinib activity in ES are also available.…”