Focus V (anlotinib)

P2, N=300, Recruiting, Tianjin Medical University Second Hospital

The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations.

P=N/A, N=80, Recruiting, Hunan Cancer Hospital

To the best of our knowledge, this is the first clinical case report in the literature describing the benefit of anlotinib and sintilimab treatment for non-small cell lung cancer with RET fusion and high PD-L1 expression. This study explores the biomarker selection for targeted therapy and combined immunotherapy in NSCLC patients.

P2, N=40, Completed, Sun Yat-sen University | Active, not recruiting --> Completed | Trial completion date: Oct 2026 --> Dec 2024

He was given sintilimab and anlotinib as first line treatment...Subsequently, the second line regimen was modified to etoposide and cisplatin (EP) combined with anlotinib and penpulimab...Notably, the patient's progress-free survival (PFS) exceeds 7 months and the overall survival up to 12 months. Our case implies that a combination of chemotherapy, anlotinib, and penpulimab might offer a promising therapeutic approach for PD-L1-negative thoracic SMARCA4-UT.

P2, N=29, Completed, Zhejiang Cancer Hospital | Recruiting --> Completed | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2021 --> Sep 2024

In conclusion, osteosarcoma with high expression of VEGFR2, PDGFRβ and CD31 is more sensitive to anlotinib. However, the potential of synergistic effect of anlotinib and chemotherapy in osteosarcoma patients needs further investigation.

P3, N=648, Active, not recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2026

In conclusion, toripalimab plus anlotinib is well tolerated and shows promising efficacy in patients with RM-NPC, and ctDNA could be a potential predictive biomarker. The trial is registered at ClinicalTrials.gov (NCT04996758).

In HCC cells, knockdown of DHFR or treatment with pralatrexate enhanced the sensitivity of HCC cells to molecularly targeted agents, such as sorafenib, regorafenib, lenvatinib, cabozantinib, or anlotinib...Therefore, pralatrexate upregulates the sensitivity of HCC cells to molecularly targeted drugs. These results expand our understanding of folate metabolism and HCC and can help provide more options for HCC treatment.

Tail effect is a golden tail of immunotherapy. This case illustrates that the tail effect of immunotherapy can offer substantial survival benefits for patients with unresectable advanced lung cancer who have failed chemotherapy.

P2, N=45, Not yet recruiting, The First Affiliated Hospital with Nanjing Medical University

P1, N=448, Not yet recruiting, Hansoh BioMedical R&D Company

P2, N=100, Recruiting, Nanfang Hospital, Southern Medical University | Trial completion date: Jul 2024 --> Sep 2027 | Trial primary completion date: Mar 2023 --> Jun 2025

Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway, suggesting a potentially new option for NSCLC treatment.

This result was superior to the second-line treatment with nab-paclitaxel, which resulted in a PFS of 8 months and best overall response of stable disease with slight shrinkage. The present case indicates that a combination of utidelone with apatinib/anlotinib exhibited antitumor activity in a patient with HR+/HER2- mBC with BMs. Therefore, this combination offers a promising therapeutic option for the clinical treatment of patients with breast cancer and BMs.

Firstly, we describe the patient's treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient's fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed...However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023. Furmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.

P=N/A, N=30, Recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University

P4, N=97, Recruiting, The First Affiliated Hospital of USTC (Anhui Provincial Hospital); The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

P3, N=142, Not yet recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P2, N=30, Not yet recruiting, Gansu Provincial Maternal and Child Health Care Hospital/Gansu Provincial Central Hospital; Gansu Provincial Maternal and Child Health Care Hospital/G

P2, N=40, Not yet recruiting, Affiliated Cancer Hospital of Shandong First Medical University; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandon

P2, N=42, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=61, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=57, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

P2, N=51, Not yet recruiting, Hebei Medical University Fourth Hospital

However, its potential synergistic effects with DDP (cisplatin) in breast cancer (BRCA) remain to be fully elucidated. In vivo study further support these results, showing that anlotinib markedly inhibits tumor growth in xenografted mice. This study confirms the efficacy of anlotinib or in combination with DDP and elucidates the mechanism behind anlotinib's effectiveness, highlighting its role in inhibiting the JAK2/STAT3 pathway.

Grade 3/4 treatment-related AEs were observed in two patients (4.8%). A combination of low-dose anlotinib and immune checkpoint inhibitors as second-line or later treatment for ES-SCLC may achieve longer PFS and OS and have manageable AEs.

P2/3, N=206, Not yet recruiting, Sun Yat-sen University

This case underscores the transient efficacy of targeted therapy in SMARCA4-deficient NSCLC with concurrent EGFR mutations. It highlights the need for continuous therapeutic adjustments and emphasizes the importance of further research into effective strategies for treating this complex and challenging subset of NSCLC, as current modalities have limitations in sustained efficacy.

P1, N=5, Recruiting, Second Xiangya Hospital of Central South University

Significant tumor microenvironment changes were observed in pCR patients, including reduced VEGF+ cells and CD4+Foxp3+ Treg cells, and increased perivascular CD4+ T cells, CD39+CD8+ T cells, and M1 macrophages. In conclusion, perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment (ClinicalTrials.gov NCT05400070).

P2, N=56, Not yet recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

The combination of anlotinib and TQB2450 is effective and tolerable in ASPS patients. TLS may serve as a prognostic biomarker, meriting further investigation.

Dose adjustment due to AEs occurred in 17.9% of patients. Anlotinib combined with WBRT is effective and well-tolerated in patients with NSCLC with multiple BMs.

FNCLCC grade, R 0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.

Anlotinib is a small molecular multi-target tyrosine kinase inhibitor, which can inhibit the activity of kinases including vascular endothelial growth factor receptor 2/3 (VEGFR2/3), fibroblast growth factor receptor 1-4 (FGFR1-4), platelet-derived growth factor receptor α/β (PDGFRα/β), and c-Kit. The patient achieved partial response and the progression-free survival was 3.8 months.

For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

P3, N=528, Active, not recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Jun 2023 --> Dec 2025 | Trial primary completion date: Jun 2023 --> Jun 2025

However, it also represents the first reported case of fatal hemoptysis with this specific treatment regimen. This finding emphasizes the need for increased awareness of this potential complication, especially in patients with centrally located PSC treated with anti-angiogenic agents like anlotinib.

Combination kinase inhibitors with immunotherapy as first-line therapy are safe and effective for the treatment of unresectable ATC, especially with BRAF V600E mutation.