Focus V (anlotinib)

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

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

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

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.

Our study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy.

The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of resistant cells, which also inhibited tumor growth, exerted anti-tumor activity, and ultimately reversed osimertinib resistance in mice. The co-administration of osimertinib and anlotinib demonstrated their synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients, ultimately reversing osimertinib resistance.

P2, N=104, Not yet recruiting, RenJi Hospital

P2, N=40, Active, not recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P2, N=194, Recruiting, Xijing Hospital

P4, N=240, Not yet recruiting, The Second Affiliated Hospital of Xi'an Jiaotong University; The Second Affiliated Hospital of Xi'an Jiaotong University

P2, N=33, Not yet recruiting, Affiliated Hospital of Jiangnan University; Affiliated Hospital of Jiangnan University

P2, N=20, Not yet recruiting, Nanjing Drum Tower Hospital; Nanjing Drum Tower Hospital

P2, N=148, Recruiting, Tianjin Medical University Cancer Institute and Hospital | Trial completion date: Mar 2026 --> Dec 2028 | Trial primary completion date: Sep 2025 --> Dec 2027

However, longer follow-up is needed for a more comprehensive efficacy assessment. ClinicalTrials.gov NCT04066543.

The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

Our bioinformatic analysis revealed a potential positive relationship between the ECM pathway and gefitinib resistance, poor treatment outcomes for programmed death 1 (PD-1) targeting, and unfavourable prognosis following chemotherapy in lung cancer patients. These findings suggest that, in addition to its antiangiogenic and vessel normalization effects, anlotinib can increase the distribution and retention of antitumour drugs in tumours by modulating ECM expression and physical properties through the RhoA/ROCK signalling pathway. These valuable insights contribute to the development of combination therapies aimed at improving tumour targeting in cancer treatment.

P2, N=44, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China

After the standard first-line treatment including albumin-bound paclitaxel, trastuzumab and pertuzumab, and a second-line treatment involving pyrotinib, capecitabine, and radiotherapy did not produce the desired results, the patient was then administered anlotinib in combination with pyrotinib and letrozole as a third-line treatment, which led to a partial response (PR). The findings suggest that anti-angiogenic therapy, specifically anlotinib, could be regarded as a promising therapeutic option for BC patients with BM.