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Background: Retroperitoneal liposarcoma (RLPS) typically shows limited response to standard chemotherapy, presenting a challenge in treating advanced or metastatic RLPS. Objective: This study aimed to evaluate the potential advantages of a combined therapeutic strategy utilizing eribulin, anlotinib, and camrelizumab. Design: Between December 2020 and March 2023, this retrospective study enrolled patients with advanced or metastatic RLPS who received treatment at Peking University Cancer Hospital Sarcoma Center. The treatment regimen involved eribulin plus anlotinib and camrelizumab administered every 3 weeks (Q3W). Methods: Efficacy was assessed following the Response Evaluation Criteria in Solid Tumors version 1.1, while safety was evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Results: The study included 47 patients with RLPS with a median age of 55.5 years. Patients received a median of 4.5 (range, 2-21) cycles of treatment. Notably, partial response was observed in 8 patients (18.2%), while 25 (56.8%) exhibited stable disease. The objective response rate (ORR) and disease control rate were 18.2% and 75%, respectively. Significant differences in ORR were observed among histological subtypes (well-differentiated vs de-differentiated vs myxoid: 0 vs 17.9% vs 50%; p = 0.039). Six patients underwent surgery before disease progression, and one patient with myxoid liposarcoma (MLPS) had a pathological complete response. With a median follow-up of 21.8 (range, 2.7-30.7) months, the median progression-free survival (mPFS) was 6.9 (95% confidence interval (CI), 4.7-9.1) months, and the 6-month PFS rate was 60.5%. Based on various histological subtypes, the mPFS was 8.4 (95% CI, 4.1-12.7) months with well-differentiated liposarcoma, 5.8 (95% CI, 3.3-8.3) months with de-differentiated liposarcoma and not reached with MLPS, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 36 (76.6%) patients, with grade 3 or higher TRAEs in 21 (44.7%) patients. The most common TRAEs were neutropenia (53.2%), proteinuria (21.3%), and anorexia (21.3%). Conclusion: The combined treatment strategy involving eribulin, anlotinib, and camrelizumab showed promising efficacy and manageable safety in patients with advanced or metastatic RLPS, particularly in those with MLPS.
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Background: Anlotinib hydrochloride is a potent oral multitargeted tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4, and PDGFR α/ß, demonstrating significant antiangiogenic activity. Transcatheter arterial chemoembolization (TACE) is considered the effective treatment for intermediate/advanced hepatocellular carcinoma (HCC), which remains a major global health challenge. This study evaluated the relative efficacy and safety of combining anlotinib with TACE against the standard TACE monotherapy among patients with intermediate or advanced HCC. Methods: This phase II randomized controlled trial included 38 patients diagnosed with intermediate or advanced HCC. Patients were randomly assigned to receive either TACE in combination with anlotinib or TACE alone. The primary endpoint of the study was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. This trial aimed to determine whether the addition of anlotinib could extend PFS and improve other clinical outcomes compared to TACE alone. Results: The median PFS for patients treated with TACE and anlotinib was significantly longer at 11.04 months compared to 6.87 months in the TACE-alone group [hazard ratio (HR) 0.46; P=0.02], indicating a robust enhancement in disease management. Although the median OS was not reached at the time of analysis, early trends suggest potential improvement. Both treatment groups had comparable ORR and DCR, demonstrating effective disease control. The safety profile of the combined treatment was manageable, with side effects similar in nature to those observed with TACE alone but not significantly more severe, thus maintaining patient quality of life. Conclusions: The addition of anlotinib to TACE appears to provide a safe and effective therapeutic benefit for patients with intermediate or advanced-stage HCC. However, longer follow-up is needed for a more comprehensive efficacy assessment. Trial Registration: ClinicalTrials.gov NCT04066543.
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Background: Involvement of the distal fibula by alveolar soft-part sarcoma is rare. Extensive resection or amputation may be needed; however, distal fibula resection can disrupt foot and ankle biomechanics, leading to ankle joint instability. Reports on joint preservation for maintaining optimal ankle joint function are scarce. Computer-aided design and individualized three-dimensional (3D)-printed uncemented implants represent an evolving solution for reconstructing the distal fibula. Case presentation: A 34-year-old woman was diagnosed with alveolar soft-part sarcoma in the right lower leg involving the cortical bone of the fibula. After anlotinib treatment, the tumor size decreased, and the tumor response rate was a partial response (PR); however, the patient continued to experience adverse reactions. With multiple disciplinary team discussions, surgical resection was deemed appropriate. Due to the extensive defect and ankle joint instability after resection, a custom-made 3D-printed prosthesis was designed and fabricated to reconstruct the defect, preserving the lateral malleolus. During the follow-up, the patient achieved favorable ankle function, and no prosthesis-related complications were observed. Conclusion: 3D-printed personalized uncemented implants constitute a novel approach and method for addressing the reconstruction issues of the distal fibula and ankle joint. Through the personalized design of 3D-printed prostheses, the lateral malleolus can be preserved, ensuring the normal anatomical structure of the ankle joint. They achieve a well-integrated interface between the prosthesis and bone, ensuring satisfactory postoperative function. Additionally, they offer valuable insights for reconstructing distal bone defects near joints in the extremities. However, confirming these findings requires extensive cohort studies.
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Anlotinib has strong antiangiogenic effects and leads to vessel normalization. However, the "window period" characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs. In this study, through RNA sequencing (RNA-seq) and label-free quantitative proteomics analysis, we discovered that anlotinib regulated the expression of components of the extracellular matrix (ECM), leading to a significant reduction in ECM stiffness. 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. We administered anlotinib in combination with these antitumour drugs and visualized their distribution using fluorescent labelling in various tumour types. Notably, our results demonstrated that anlotinib prolonged the retention time and distribution of antitumour drugs at the tumour site. Moreover, the combination therapy induced notable loosening of the tumour tissue structure. This reduction was associated with decreased interstitial fluid pressure and tumour solid pressure. Additionally, we observed that anlotinib effectively suppressed the Ras homologue family member A (RhoA)/Rho-associated protein kinase (ROCK) signalling pathway. 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.
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Background: Adrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC. Case presentation: We report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm × 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient's lung metastases and the left adrenal gland area mass (39mm × 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism. Conclusion: This case highlights the remarkable response of our patient's ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma.
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Brain metastases (BM) represent a common and severe complication of breast cancer (BC), emerging in approximately 10%-16% of all BC patients. The prevalent approach for treating BC patients with BM encompasses a multimodal strategy, combining surgery, whole brain radiation therapy, and stereotactic radiosurgery. Yet, a concrete guideline for localized treatment strategies remains elusive, while systemic treatments like small-molecule-targeted therapy and immunotherapy are still in the clinical trial phase. This case study presents a significant clinical response to anlotinib treatment in a patient with estrogen receptor-negative, progesterone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, complicated by BM. 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.
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Advanced non-small cell lung cancer (NSCLC) remains a significant clinical challenge, particularly in patients who exhibit stable disease (SD) following first-line chemotherapy combined with immunotherapy. This study aims to evaluate the efficacy and safety of Anlotinib, a novel multitarget tyrosine kinase inhibitor, as maintenance therapy in this patient cohort. This retrospective, single-center study enrolled patients with advanced NSCLC who showed SD after receiving a combination of first-line chemo-immunotherapy for 4 cycles, then add anlotinib to subsequent standard maintenance therapy, continuing treatment until disease progression or the occurrence of intolerable toxic side effects. The primary endpoint was progression-free survival (P FS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. A total of 52 patients were enrolled, the median P FS and OS was 5.0m and 10.0m, respectively. The ORR and DCR was 28.85% and 67.31%. subgroup analysis indicated that its efficacy correlate with certain Adverse Effects (AEs, such as hypertension, proteinuria, and hand-foot syndrome). Further mechanistic analysis suggests that this regimen may likely reduce immune suppression by depleting Tregs, thereby further activating the immune system to exert synergistic anti-tumor effects. Besides promising efficacy, the toxicity can be tolerated. Anlotinib demonstrates promising efficacy as a maintenance therapy in patients with advanced NSCLC who have achieved SD following first-line chemotherapy combined with immunotherapy. The manageable safety profile and the observed extension in P FS and OS suggest that Anlotinib could be a valuable therapeutic option for this challenging patient population. Further large-scale randomized controlled trials are warranted to confirm these findings and to optimize patient selection and management strategies.
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Breast cancer with brain metastasis accounts for the second largest number of brain metastases among solid malignancies. Despite advances in HER2-targeted therapy, 50% of patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer develop brain metastases and are associated with poor outcomes. In this article, we report the case of a patient with HER2+ metastatic breast cancer who developed brain metastases, despite experiencing a durable effect on extracranial metastases after treatment with trastuzumab and pertuzumab. The patient exhibited intracranial progression while receiving treatment with trastuzumab deruxtecan monotherapy after secondary brain radiotherapy and multiple lines of therapy with anti-HER2 agents, such as pyrotinib, lapatinib, tucatinib, and ado-trastuzumab emtansine. However, the administration of anlotinib (an antiangiogenesis medication) and trastuzumab deruxtecan resulted in intracranial and extracranial partial response and was linked to manageable side effects. The present case indicates that the combination of anlotinib and trastuzumab deruxtecan may be a promising treatment option for patients with HER2+ breast cancer with brain metastasis. Nevertheless, further studies are warranted to verify the present findings.
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Objective: The aim of this study was to investigate whether anlotinib could exert an inhibitory effect on the proliferation and invasion of cervical cancer cells by inhibiting cytokines secreted by activated cancer-associated fibroblasts (CAFs). Methods: CAFs were isolated from cervical cancer tissues and experimentally studied in vivo and in vitro. Molecular biology experimental methods were used to verify whether anlotinib could inhibit the pro-carcinogenic effects of CAFs derived from cervical cancer tissues. Results: CAFs promote the proliferation and invasion of cervical cancer cells. Anlotinib inhibited the activation of CAFs and suppressed the promotion of cervical cancer cells by CAFs. Anlotinib inhibited the expression of multiple cytokines within CAFs and suppressed the release of interleukin (IL)-6 (IL-6) and IL-8. In vivo studies have shown that anlotinib diminished the growth of xenografted cervical cancer cells, and treatment in combination with docetaxel had an even more significant tumor growth inhibitory effect. Conclusion: Anlotinib inhibits the pro-cancer effects of CAFs by suppressing the activation of CAFs and the secretion of pro-cancer cytokines. Our findings suggest that the combination of anlotinib and docetaxel may be a potential strategy for the treatment of refractory cervical cancer.
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BACKGROUND: Small cell lung cancer (SCLC) exhibits a pronounced tendency for metastasis and relapse, and the acquisition of resistance to chemotherapy and radiotherapy, leading to complexity in treatment outcomes. It is crucial to tackle these challenges by advancing targeted therapeutic approaches in ongoing research endeavors. Variant RET fusions have been reported in several solid tumors, but are rarely reported in SCLC. CASE SUMMARY: We present the first case of a KIF5B-RET fusion in a 65-year-old male patient with SCLC. To date, the patient has received the 4th line chemotherapy with anlotinib for one year and has shown a sustained favorable partial response. According to the results of next generation sequencing, this SCLC patient harbors the KIF5B-RET fusion, suggesting that RET fusion could serve as a promising molecular target for SCLC treatment. Next-generation sequencing (NGS) plays a critical role in comprehensively assessing the genotype and phenotype of cancer. CONCLUSION: NGS can provide SCLC patients with personalized and targeted therapy options, thereby improving their likelihood of survival.
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BACKGROUND: Immune-checkpoint inhibitors are now used more commonly in combination than monotherapy as the first-line choice in patients with unresectable advanced melanoma. Nevertheless, for cases that progressed after the initial combination therapy, the subsequent regimen option can be very difficult. Herein, we reported the efficacy and safety of a triple combination regimen in Chinese unresectable advanced melanoma patients who had poor responses to the first-line immune therapy. METHODS: We reviewed the clinical profiles of patients diagnosed with stage IIIC-IV melanoma between June 1, 2020, and September 30, 2023. The patients who failed the prior immune therapies and received anti-PD-1 mono antibody plus interferon(IFN)-alpha 1b and anlotinib hydrochloride as the second-line therapy were enrolled in the retrospective analysis. Additionally, we examined the exhaustion of T-cells using mIHC staining in available tumor samples. RESULTS: Fifty-five patients were included in this study. The median follow-up period was 13.6 months. The objective response rate evaluated by the investigators was 9.1%(1CR, 4PR). The disease control rate was 47.3%. The median overall survival was 17.6 months, and the median progression-free survival was 2.8 months. The adverse events rate of any grade was 100%. Grade 3 or 4 irAEs were observed in 29.1% of cases. Multiplex immunohistochemical staining revealed an increased trend of TIM3 expression on tumor-infiltrating T cells in patients without objective response. CONCLUSION: PD-1 monoclonal antibody plus interferon-alpha 1b plus anlotinib showed acceptable tolerability and anticancer benefits in Chinese metastatic melanoma patients as a second-line therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Indoles , Melanoma , Receptor de Muerte Celular Programada 1 , Quinolinas , Humanos , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/mortalidad , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Indoles/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Anciano , Adulto , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Interferón-alfa/uso terapéutico , Interferón-alfa/administración & dosificación , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
There are no standard third-line or beyond treatments for patients with driver mutation-positive advanced lung adenocarcinoma (LUAD). Anlotinib was approved as a third-line multitarget drug in China in 2018. Limited data are available regarding the efficacy and safety of anlotinib compared with chemotherapy. To investigate the efficacy and safety of anlotinib compared with traditional chemotherapy in patients with epidermal growth factor receptor (EGFR)-positive advanced LUAD. We conducted a retrospective study of 83 EGFR mutation-positive patients with advanced LUAD between 2011 and 2022. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, whereas the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Anlotinib-related adverse events (AEs) were recorded to evaluate the safety of anlotinib. 39 patients with LUAD received anlotinib and 44 patients with LUAD received chemotherapy were enrolled in the study. Patients treated with anlotinib exhibited longer PFS (11.2 vs 4.5 months, P < .01) and OS (18.8 vs 15.8 months, P < .05) than patients treated with chemotherapy. There were no significant differences in ORR (7.9% vs 20.5%, P = .129) or DCR (100% vs 93.2%, P = .120) between the two groups. Anlotinib-related AEs grading 3-4 level were observed in 2 (5.1%) patients, no anlotinib-related death was recorded. Cox regression analyses of PFS and OS showed that brain metastases and age < 30 years at diagnosis had negative effects on clinical outcomes. Anlotinib is effective and safe in patients with EGFR-positive advanced LUAD. Patients without brain metastases had better clinical outcomes.
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Adenocarcinoma del Pulmón , Receptores ErbB , Indoles , Neoplasias Pulmonares , Quinolinas , Humanos , Masculino , Femenino , Indoles/uso terapéutico , Indoles/efectos adversos , Indoles/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Persona de Mediana Edad , Receptores ErbB/genética , Receptores ErbB/metabolismo , Anciano , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Estudios Retrospectivos , Adulto , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Resultado del Tratamiento , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Estadificación de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversosRESUMEN
Background: Small cell lung cancer (SCLC) presents considerable challenges regarding the availability of second-line treatment options, which remain limited. The paucity of effective therapeutic choices at this setting emphasizes the urgent requirement for rigorous research and investigation into novel treatment strategies. To address this clinical gap, the current study aimed to compare the efficacy and safety of anlotinib with the standard second-line treatment, topotecan, in patients with relapsed SCLC. Methods: This retrospective collected data from SCLC patients who received either anlotinib or topotecan as second-line treatment. The primary endpoints were progression-free survival (PFS), while the secondary endpoints included the overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety assessment. Results: The study included 46 SCLC patients, with 20 receiving anlotinib and 26 receiving topotecan as second-line treatment. The anlotinib group showed a significantly longer median PFS compared to the topotecan group [5.6 vs. 2.2 months; hazard ratio (HR) =0.50; 95% confidence interval (CI): 0.27-0.92; P=0.02]. However, there was no statistically significant difference in OS between the two groups (9.1 vs. 7.7 months; HR =0.88; 95% CI: 0.46-1.70; P=0.71). The ORRs were 20.0% and 7.7% (P=0.48), and the DCRs were 70.0% and 23.1% (P=0.007) for the anlotinib and topotecan groups, respectively. Treatment-related adverse events (TRAEs) occurred in 13 patients (65.0%) in the anlotinib group and 20 (76.9%) in the topotecan group (P=0.49). Conclusions: Anlotinib shows the potential to extend PFS and manageable adverse events (AEs) compared to topotecan in the second-line setting for relapsed SCLC.
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Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.
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Patients with recurrent or metastatic head and neck cancers (R/M HNCs) are prone to developing resistance after immunotherapy. This retrospective real-world study aims to investigate whether the addition of anlotinib can reverse resistance to PD-1 inhibitors (PD-1i) and evaluate the efficacy and safety of this combination in R/M HNCs. Main outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Potential biomarkers included PD-L1 expression, lipid index, and genomic profiling. Twenty-one patients with R/M HNCs were included, including 11 nasopharyngeal carcinoma (NPC), five head and neck squamous cell carcinoma (HNSCC), three salivary gland cancers (SGC), and two nasal cavity or paranasal sinus cancers (NC/PNC). Among all patients, ORR was 47.6% (95% CI: 28.6-66.7), with 2 (9.5%) complete response; DCR was 100%. At the median follow-up of 17.1 months, the median PFS and OS were 14.3 months (95% CI: 5.9-NR) and 16.7 months (95% CI:8.4-NR), respectively. The median DOR was 11.2 months (95% CI: 10.1-NR). As per different diseases, the ORR was 45.5% for NPC, 60.0% for HNSCC, 66.7% for SGC, and 50.0% for NC/PNC. Most treatment-related adverse events (TRAEs) were grade 1 or 2 (88.9%). The most common grades 3-4 TRAE was hypertension (28.6%), and two treatment-related deaths occurred due to bleeding. Therefore, adding anlotinib to the original PD-1i could reverse PD-1 blockade resistance, with a favorable response rate, prolonged survival, and acceptable toxicity, indicating the potential as a second-line and subsequent therapy choice in R/M HNCs.
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Resistencia a Antineoplásicos , Neoplasias de Cabeza y Cuello , Inhibidores de Puntos de Control Inmunológico , Indoles , Recurrencia Local de Neoplasia , Quinolinas , Humanos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Quinolinas/uso terapéutico , Anciano , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Indoles/uso terapéutico , Adulto , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Metástasis de la NeoplasiaRESUMEN
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as icotinib, osimertinib, and aumolertinib have emerged as promising treatment options for EGFR mutated Non-small cell lung cancer (NSCLC) patients. Additionally, anlotinib, an anti-angiogenic agent targeting VEGFR, FGFR, and PDGFR, has been used in combination with EGFR-TKIs in NSCLC cases. A method utilizing ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for quantifying icotinib, osimertinib, aumolertinib and anlotinib simultaneously in clinical TDM. The chromatographic separation was performed using a Kinetex C18 column (100â¯mm × 2.1â¯mm) and an elution gradient of ammonium acetate in water acidified with 0.1â¯% formic acid and in acetonitrile. The assay was validated over a linear range of 4-2000â¯ng/mL for icotinib, 2-1000â¯ng/mL for osimertinib, 1-500â¯ng/mL for aumolertinib, and 0.8-400â¯ng/mL for anlotinib, following the guidelines on bioanalytical methods by FDA. The quantification method exhibited satisfactory performance in terms of selectivity, accuracy (from 91.3â¯% to 107â¯%), precision (intra- and inter-day coeffficients of variation ranged from 0.944â¯% to 7.48â¯%), linearity, recovery (from 86.0â¯% to 91.9â¯%), matrix effect (IS-normalized matrix factors were from 96.7â¯% to 102â¯%), and stability. Overall, the method proved to be sensitive, reliable, and straightforward, enabling successful simultaneous determination of blood concentrations of icotinib, osimertinib, aumolertinib, and anlotinib in patients. The validity of the method has been confirmed across various instruments.
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Acrilamidas , Compuestos de Anilina , Éteres Corona , Monitoreo de Drogas , Indoles , Quinazolinas , Quinolinas , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Quinolinas/sangre , Quinolinas/uso terapéutico , Quinolinas/farmacocinética , Indoles/sangre , Indoles/farmacocinética , Indoles/uso terapéutico , Cromatografía Líquida de Alta Presión/métodos , Monitoreo de Drogas/métodos , Acrilamidas/sangre , Compuestos de Anilina/sangre , Quinazolinas/sangre , Quinazolinas/uso terapéutico , Quinazolinas/farmacocinética , Inhibidores de Proteínas Quinasas/sangre , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/uso terapéutico , Reproducibilidad de los Resultados , Antineoplásicos/sangre , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacocinética , Pirazinas/sangre , Pirazinas/farmacocinética , Pirazinas/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/sangre , Cromatografía Líquida con Espectrometría de Masas , Benzamidas , PirimidinasRESUMEN
Objective: To study the clinical effects of anlotinib combined with second-line chemotherapy (SLC) on immunosuppression in patients with advanced non-small cell lung cancer (NSCLC). Methods: In this retrospective study, the medical records of 106 patients with advanced NSCLC admitted to the Lianyungang First People's Hospital from November 2020 to March 2022 were retrospectively analyzed. Amongst 106 patients, 53 patients received second-line single-agent chemotherapy regimens (SLC group), and 53 patients received anlotinib combined with SLC (ASLC group). Prognosis, levels of immune cells and inflammatory cytokine, and adverse reactions were analyzed. Results: Clinical efficacy of the ASLC group was significantly higher than the SLC group (p<0.05). After treatment, patients in the ASLC group exhibited significantly higher levels of CD4+/CD8+ and CD4+ compared to those in the SLC group (p<0.05), while the difference in CD8+ level between the two groups was not statistically significant (p>0.05). After treatment, levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6) in the ASLC group were lower compared to the SLC group (p<0.05). Conclusion: In patients with advanced NSCLC, anlotinib combined with SLC is associated with higher levels of immune cells and reduced inflammatory factors. This treatment regimen, thus, can reduce immunosuppression and improve the prognosis of NSCLC patients.
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Background: Existing research data indicates that albumin-bound paclitaxel (nab-ptx), anlotinib, and PD-1/L1 inhibitors have individually shown efficacy in second-line and subsequent treatments for advanced non-small cell lung cancer (NSCLC). This study seeks to investigate the potential of an optimized treatment regimen in this context by combining these three drugs and evaluating both efficacy and safety outcomes. Patients and Methods: Between January 2020 and January 2022, we collected data from pre-treated advanced NSCLC patients who received a combination therapy of nab-ptx, anlotinib, and PD-1/L1 inhibitors as a second-line or later treatment. The primary endpoints for the study included the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR) and overall survival (OS), while adverse events (AEs) were also recorded. Results: Our findings revealed that the ORR of this regimen in pretreated NSCLC patients was 35.71%, with mean PFS of 5.0 months and mean OS of 10.0 months. Further analysis suggested correlations between the efficacy of the regimen and factors such as PD-L1 expression levels, the occurrence of certain types of adverse events, and the status of NK cell activity. Additionally, the tolerable toxicity profile of this regimen indicates its potential applicability in the treatment of pretreated advanced NSCLC. Conclusion: Our study displayed that triple-drug combination of nab-ptx, anlotinib and PD-1/L1 inhibitors showed promising efficiency and tolerated cytotoxicity in the 2nd or above line treatment of advanced NSCLC, indicating the potential of such regimen as an important option for second-line treatment of advanced NSCLC. However, due to limitations in patient numbers, its actual clinical value awaits further research confirmation.
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BACKGROUND: Treatments are limited for extensive stage small cell lung cancer (ES-SCLC) patients in secondline or subsequent setting. This study aimed to explore the clinical efficacy and safety of immune checkpoint inhibitors (ICIs) plus anlotinib as secondline or subsequent therapy in ES-SCLC. METHODS: We retrospectively analyzed 116 patients with ES-SCLC at Shandong Provincial Qianfoshan Hospital between January 2019 and March 2024. According to the different therapy regimes, they were divided into three groups, ICI plus anlotinib as secondline or subsequent therapy group (ICI + anlotinib group), single ICI as secondline or subsequent therapy group (single ICI therapy group), single chemotherapy as secondline therapy group (single chemotherapy group). Kaplan-Meier method was used to compare the progression-free survival (PFS) and the overall survival time (OS) among these three groups. Cox regression analysis was used to analyze different factors which correlated to PFS and OS. The adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Kaplan-Meier analysis showed that patients in ICI + anlotinib group had a longer PFS and OS compared to patients in single ICI therapy group (median PFS [mPFS]: 6.7 months vs. 4.6 months, P = 0.007; median OS [mOS]:12.4 months vs. 8.4 months, P = 0.041) and single chemotherapy group (mPFS: 6.7 months vs. 3.0 months, P < 0.001; mOS: 12.4 months vs. 7.2 months, P = 0.002). The Cox regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), liver metastasis, brain metastasis and treatment regimes were independent predictors that affecting the PFS and OS of all the enrolled patients. The common adverse events (AEs) were wleukopenia and fatigue. There was no significant statistical difference in other AEs among the three groups except for leukopenia. CONCLUSION: ICI + anlotinib as secondline or subsequent therapy has better efficacy than single ICI group and single chemotherapy group and with tolerable toxicities for patients with ES-SCLC.
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Background: Currently, chemotherapy plus immunotherapy followed by maintenance therapy with immune monotherapy is the preferred first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), but with limited overall survival (OS) and progression-free survival (PFS) benefits. The combination of anti-angiogenic drugs with immunotherapy has shown encouraging anti-tumor activity and tolerability, with some degree of overcoming immune resistance. This study aimed to evaluate the effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC. Methods: Between June 2020 and December 2021, 12 patients with newly diagnosed ES-SCLC in the First Affiliated Hospital of Army Medical University were retrospectively analyzed. All patients without disease progression after 4-6 cycles of first-line platinum-containing chemotherapy plus anti-PD-1/PD-L1 antibodies received anlotinib (12 mg oral/day, days 1-14, followed by 1 week off, every 3 weeks per cycle) plus anti-PD-1/PD-L1 antibodies as maintenance therapy. Several patients underwent chest radiotherapy (intensity-modulated radiotherapy using a 6 MV X-ray) without disease progression before maintenance therapy. The effectiveness and safety of anlotinib plus anti-PD-1/PD-L1 antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC were evaluated. Results: The median follow-up time was 31.1 months. During first-line treatment (including maintenance therapy), one patient achieved a complete response, eight patients achieved a partial response (PR), and three patients had stable disease, with an objective response rate of 75.0% and a disease control rate of 100.0%. During maintenance therapy with anlotinib plus anti-PD-1/PD-L1 antibodies, 50.0% of patients achieved further lesion remission on the basis of the prior initial treatment, of which one patient achieved a PR. The median PFS was 13.6 [95% confidence interval (CI): 11.2-15.6] months, and the median OS was 19.5 (95% CI: 14.5-24.5) months. Treatment-related any grade and grade 3-4 adverse events (AEs) were reported in 100.0% and 58.3% of patients, respectively. No life-threatening AEs were observed. Grade 3-4 AEs included leukocytopenia (58.3%, 7/12), thrombocytopenia (33.3%, 4/12), nausea (33.3%, 4/12), anemia (16.7%, 2/12), and fatigue (8.3%, 1/12). All AEs during maintenance therapy were tolerated and were regarded as grade 1-2, with the majority being fatigue, nausea, rash, and hemoptysis. Conclusions: The combination of anlotinib with anti-PD-1/PD-L1 antibodies demonstrated encouraging effectiveness and safety in treating patients with ES-SCLC, suggesting that it may be a preferred option for maintenance therapy after first-line chemotherapy combined with immunotherapy.