Efficacy and safety of multikinase inhibitors for patients with refractory thyroid cancer: Systematic review and network meta-analysis.

CONTEXT: Multikinase inhibitors (MKIs) improve the treatment of refractory thyroid cancer, included radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and advanced medullary thyroid carcinoma (aMTC). OBJECTIVE: This study aims to compare the efficacy of MKIs in improving survival outcomes and safety. DATA SOURCES: Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2023. STUDY SELECTION: Three independent authors selected these studies. Randomised-controlled trials that compared the use of a MKI to other MKIs or placebo were included. DATA EXTRACTION AND SYNTHESIS: This review followed PRISMA guidelines. Risk of bias was analyzed using the Cochrane RoB 2 tool. Bayesian network meta-analysis was performed. Treatments were grouped into common nodes based on the type of MKI. MAIN OUTCOMES AND MEASURES: Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate, disease control rate, clinical benefit rate, and adverse events. RESULTS: Cabozantinib 60 mg/d (CAB60) was associated with the highest prolonged PFS in RAIR-DTC patients, followed by lentivatinib 18 or 24 mg/d (LEN18 or LEN24), and apatinib. PFS was also improved in in aMTC patients received CAB 140 mg/d (CAB140), CAB60, or anlotinib. A significantly greater improvement on the performance of OS was seen in CAB60, LEN24, anlotinib, and sorafenib in RAIR-DTC patients, but which in aMTC patients were lack of statistical differences. Compared with the low-dose of MKIs, high-dose of MKIs such as CAB, LEN, and vandetanib increased the incidence of adverse events. CONCLUSION: CAB60, LEN, and apatinib are promising topical MKIs with statistically significant primary outcomes in RAIR-DTC patients, while CAB and anlotinib are effective in prolonging PFS in aMTC patients.

Efficacy and safety of apatinib plus immune checkpoint inhibitors and transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma.

PURPOSE: The evidence of apatinib plus immune checkpoint inhibitors (ICIs) and transarterial chemoembolization (TACE) for treating advanced hepatocellular carcinoma (HCC) is limited. This study aimed to compare the treatment efficacy and safety of apatinib plus ICIs and TACE with apatinib plus TACE in these patients. METHODS: This study retrospectively enrolled 90 patients with advanced HCC treated with apatinib plus TACE (A-TACE group, n = 52) or apatinib plus ICIs and TACE (IA-TACE group, n = 38). RESULTS: The objective response rate was numerically higher in IA-TACE group compared with A-TACE group without statistical significance (57.9% vs. 36.5%, P = 0.055). Disease control rate was not different between groups (86.8% vs. 76.9%, P = 0.248). Progression-free survival (PFS) was improved in IA-TACE group compared with A-TACE group (P = 0.018). The median PFS (95% confidence interval) was 12.5 (8.7-16.3) months in IA-TACE group and 8.5 (5.6-11.4) months in A-TACE group. Overall survival (OS) was also prolonged in IA-TACE group compared with A-TACE group (P = 0.007). The median OS (95% confidence interval) was 21.1 (15.8-26.4) months in IA-TACE group and 14.3 (11.5-17.1) months in A-TACE group. By multivariate Cox regression model, IA-TACE was independently associated with prolonged PFS (hazard ratio = 0.539, P = 0.038) and OS (hazard ratio = 0.447, P = 0.025). Most adverse events were not different between groups. Only the incidence of reactive cutaneous capillary endothelial proliferation was higher in IA-TACE group compared with A-TACE group (10.5% vs. 0.0%, P = 0.029). CONCLUSION: Apatinib plus ICIs and TACE may be an effective and safe treatment for patients with advanced HCC, but further large-scale studies are needed for verification.

Neoadjuvant therapy of sequential TACE, camrelizumab, and apatinib for single huge hepatocellular carcinoma (NEO-START): study protocol for a randomized controlled trial.

BACKGROUND: The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. METHODS: This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. DISCUSSION: Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. TRIAL REGISTRATION: www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

Effect and Safety of Apatinib as Neoadjuvant Therapy in Locally Advanced Differentiated Thyroid Cancer: A Phase 2 Trial.

Context: Presently, there is a paucity of prospective clinical trials investigating neoadjuvant therapy for locally advanced thyroid cancer. Objective: This study was a multicenter, open-label, single-arm, phase II trial evaluating the efficacy and safety of apatinib as neoadjuvant therapy in patients with local advanced differentiated thyroid cancer (DTC). Methods: Patients were treated with preoperative apatinib over a course of 2 to 4 cycles, culminating in surgical resection. The primary endpoints were objective response rate (ORR) and disease control rate (DCR); the secondary endpoints were the rate of R0 surgery, alterations in serum thyroglobulin levels, disease-free survival, and adverse events (AEs). Results: A total of 14 patients who met the inclusion criteria were administered neoadjuvant apatinib. Among these, 13 patients underwent surgical procedures following apatinib treatment and were enrolled in the ITT population. The ORR was 53.8% and the DCR was 100%. Of the patients, 84.6% received R0 surgery, while the remaining 15.4% underwent R1 resection. Predominant among the observed AEs were hypertension, hand-foot syndrome, hepatic dysfunction, proteinuria, and hypothyroidism, with no instances of grade 4 or 5 AEs reported. Subsequent to surgery, patients were followed up for a median period of 34 months, during which disease progression occurred in 5 individuals (35.7%), encompassing 3 cases of locoregional recurrences and 2 cases of distant metastases. Conclusion: Apatinib may be an effective agent in the use of neoadjuvant therapy for locally advanced DTC. Patients may therefore benefit from surgical outcomes and their long-term prognosis.

SOX combined with apatinib and camrelizumab in the treatment of resectable locally advanced gastric cancer: a case report.

Gastric cancer is highly prevalent in China, yet early diagnosis and overall survival rates are low. The primary treatment strategy is comprehensive therapy centered on surgery. Studies indicate that neoadjuvant chemotherapy can enhance radical resection rates and extend survival in locally advanced gastric cancer. Combining VEGFR inhibitors with chemotherapy improves efficacy in digestive system tumors, while PD-1/PD-L1 inhibitors combined with anti-angiogenesis agents or chemotherapy show synergistic effects. This report presents a case of gastric adenocarcinoma (cT3N1M0) treated with SOX, apatinib mesylate, and camrelizumab as neoadjuvant therapy, followed by D2 distal gastrectomy and postoperative adjuvant therapy with the same regimen. The patient completed all treatment cycles successfully. Post-neoadjuvant therapy, only focal residual cancer cells were found in the lamina propria (pT1a). During postoperative adjuvant therapy follow-up, gastroscopic biopsy indicated a pathological complete response with no recurrence or metastasis. The patient primarily experienced dyspepsia, oropharyngeal pain, capillary proliferation, mild bone marrow suppression, nausea, and vomiting as side effects. Therefore, SOX combined with apatinib mesylate and camrelizumab shows promise for treating resectable locally advanced gastric cancer.

Apatinib manifests an unexpectedly favorable outcome in the management of axillary lymph node follicular dendritic cell sarcoma: a case report.

We present a case of follicular dendritic cell sarcoma in the axillary lymph node, which unexpectedly showed favorable outcomes after the application of apatinib. Follicular Dendritic Cell Sarcoma (FDCS) exhibits a rare incidence and an unclear pathogenic mechanism, contributing to the limited breakthroughs in its treatment to date within the medical field. The current mainstream therapeutic approaches include surgery, CHOP(cyclophosphamide, doxorubicin, vincristine, prednisone), ICE(ifosfamide, carboplatin, etoposide), ABVD(doxorubicin, bleomycin, vinblastine, dacarbazine), and immune checkpoint inhibitors. A 38-year-old male patient was admitted to the hospital due to a lump in the right axilla and underwent surgical treatment. Postoperative pathology confirmed the diagnosis of follicular dendritic cell sarcoma. Two months post-surgery, he faced a recurrence, prompting a subsequent surgical intervention complemented by tumor radiofrequency ablation. Despite these interventions, the treatment response was suboptimal. Subsequently, the patient was treated with the CHOP regimen, but after two cycles, he developed bone metastasis. Due to the patient's limited financial resources and refusal of immunotherapy, we switched to a regimen of gemcitabine and docetaxel, but the disease progressed again after two cycles. A one-cycle trial of albumin-bound paclitaxel yielded unsatisfactory results. Ultimately, the patient was treated with Apatinib, achieving a 10-month progression-free survival. Due to the patient's limited financial circumstances, we, in the absence of guideline recommendations and evidence from evidence-based medicine, achieved a 10-month progression-free survival (PFS) solely based on experiential use of the anti-angiogenic drug, Apatinib. The purpose of this case report is to provide additional therapeutic options for FDCS treatment and to pave the way for exploring the mechanism of action of Apatinib in FDCS.

Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives.

Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC). Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC.

Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

The efficacy, safety, and beneficiary population of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer patients: A comparative cohort study.

AIM: Angiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer (RPR-OC) patients. METHODS: This study retrieved 67 RPR-OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication. RESULTS: Objective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression-free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5-6.3) months in apatinib + chemo group and 3.8 (2.0-5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5-24.5) months in apatinib + chemo group and 13.6 (8.6-18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05). CONCLUSION: Angiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR-OC patients.

Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study.

BACKGROUND: Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported. METHODS: In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. RESULTS: Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2-year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12-month progression-free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2-55.6), with an 18-month PFS rate of 37.8% (95% CI, 22.7-52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3-36.9), and the 24-month OS rate was 47.8% (95% CI, 31.7-62.3). Age > 50 years, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study. CONCLUSION: Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy. No new safety signals were noted with long-term treatment.

Immunotherapy combined with apatinib in the treatment of advanced or metastatic gastric/gastroesophageal tumors: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy or apatinib alone has been used as third-line adjuvant therapy for advanced or metastatic gastric/gastroesophageal junction (G/GEJ) tumors, but the efficacy of combining them with each other for the treatment of patients with advanced or metastatic G/GEJ is unknown; therefore, we further evaluated the efficacy and safety of immunotherapy combined with apatinib in patients with advanced or metastatic G/GEJ. METHODS: The main search was conducted on published databases: Embase, Cochrane library, PubMed.The search was conducted from the establishment of the database to December 2023.Clinical trials with patients with advanced or metastatic G/GEJ and immunotherapy combined with apatinib as the study variable were collected. Review Manager 5.4 software as well as stata 15.0 software were used for meta-analysis. RESULTS: A total of 651 patients from 19 articles were included in this meta-analysis. In the included studies, immunotherapy combined with apatinib had a complete response (CR) of 0.03 (95% CI: 0.00 -0.06), partial response (PR) of 0.34 (95% CI: 0.19-0.49), stable disease (SD) of 0.43 (95% CI: 0.32-0.55), objective response rate (ORR) was 0.36 (95% CI: 0.23-0.48), disease control rate (DCR) was 0.80 (95% CI: 0.74-0.86), and median progression-free survival (PFS) was 4.29 (95% CI: 4.05-4.52), median Overall survival (OS) was 8.79 (95% CI: 7.92-9.66), and the incidence of grade ≥ 3 TRAEs was 0.34 (95% CI: 0:19-0.49). PR, ORR, DCR, median PFS and median OS were significantly higher in the immunotherapy and apatinib combination chemotherapy group (IAC) than in the immunotherapy combination apatinib group (IA). And the difference was not significant in the incidence of SD and grade ≥ 3 TRAEs. CONCLUSION: This meta-analysis shows that immunotherapy combined with apatinib is safe and effective in the treatment of advanced or metastatic G/GEJ, where IAC can be a recommended adjuvant treatment option for patients with advanced or metastatic G/GEJ. However, more large multicenter randomized studies are urgently needed to reveal the long-term outcomes of immunotherapy combined with apatinib treatment.

A case report of low-dose apatinib in the treatment of advanced triple-negative breast cancer.

Background: The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means. Case Description: A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months. Conclusions: Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.

Apatinib and gamabufotalin co-loaded lipid/Prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis.

Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase-9 (MMP-9). In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.

Effects of Apatinib combined with Temozolomide on levels of sPD-1 and sPD-L1 in patients with drug-resistant recurrent glioblastoma.

OBJECTIVE: This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). STUDY DESIGN: A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. RESULTS: General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). CONCLUSIONS: Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.

The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. METHODS: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. RESULTS: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). CONCLUSION: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

Recent advances in tyrosine kinase inhibitors VEGFR 1-3 for the treatment of advanced metastatic melanoma.

INTRODUCTION: Increasing evidence from preclinical and clinical studies suggests the role of vascular endothelial growth factor (VEGF) signaling in melanoma progression, response to therapy, and overall survival. Moreover, the discovery of the potential involvement of the VEGF pathway in resistance to immunotherapy has led to new clinical trials with VEGFR inhibitors. AREAS COVERED: We have reviewed recent literature, mainly published within the last 5 years, on VEGFR-targeted treatments for advanced melanoma, including mucosal, acral, and uveal melanoma. The VEGFR inhibitors were used as a single therapy or combined with either immunotherapy or chemotherapy, and they were employed in treatment for KIT-mutated cutaneous melanoma and for patients with brain metastases. EXPERT OPINION: Trials involving monotherapy have been unsuccessful in demonstrating meaningful efficacy. Despite some activity, the combination of VEGFR-targeting tyrosine kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICI) in patients with ICI-resistant melanoma, the combination did not significantly improve outcomes compared to anti-PD-1 monotherapy in the first-line settings. On the contrary, some patients with mucosal, acral or KIT-mutant melanoma may benefit from TKI-based therapies. Further studies focused on biomarker discovery and randomized trials are necessary to better understand the role of VEGFR1-3 as a therapeutic target in melanoma.

Apatinib beyond first progression is associated with prolonged overall survival in patients with advanced breast cancer: Results from an observational study.

In the present study, the efficacy and safety of a low dose of apatinib in the treatment of patients with advanced breast cancer (ABC) in a real-world setting were assessed, the impact of continuous anti-angiogenic therapy beyond progression was determined and the factors associated with efficacy were evaluated. A total of 63 patients with ABC who were treated with apatinib and for whom several lines of treatment had failed were retrospectively analyzed in Tangshan People's Hospital (Tangshan, China) between January 2016 and October 2022. Apatinib was administered orally combined with chemotherapy, endocrine therapy, targeted therapy or monotherapy at a dose of 250 mg per day. Apatinib administration was continued in certain patients beyond first progressive disease (PD), and these patients were defined as the continued anti-angiogenic treatment beyond first progression (CABF) group, while those who discontinued apatinib were defined as the non-CABF group. In the evaluation of the first efficacy, the objective response rate was 33.3%. A total of 26 patients continued to receive apatinib post-first PD and were allocated to the CABF group. The median overall survival (OS) time of the 63 patients was 16 months. Log-rank univariate analysis revealed that the OS time was significantly associated with molecular subtype (P=0.014), CABF (P=0.004), and the neutrophil-to-lymphocyte ratio (NLR) (P=0.011). Multivariate Cox regression analysis revealed that being in the non-CABF group and a high NLR were independent risk factors for lower OS time (P=0.017 and P=0.041, respectively). These results support the continued administration of low-dose apatinib beyond progression and the use of NLR as an easily accessible prognostic marker in patients with ABC treated with apatinib.

Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Resection of unresectable hepatocellular carcinoma after conversion therapy with apatinib and camrelizumab: a case report and literature review.

Hepatocellular carcinoma is a rather common malignant tumor. Most patients with hepatocellular carcinoma receive their diagnosis at an advanced stage, at which surgical resection is no longer appropriate. A growing body of research has demonstrated the value of convention therapy for patients with intermediate-stage hepatocellular carcinoma, while specific application protocols and treatment guidelines are not well developed. Emerging clinical researches suggest that a tyrosine kinase inhibitor in combination with an immune checkpoint inhibitor is a reasonable strategy for unresectable hepatocellular carcinoma. However, there are relatively few reports on the efficacy of apatinib and camrelizumab in the treatment of hepatocellular carcinoma. We were able to successfully remove one patient's hepatocellular carcinoma after 8 cycles of conversion therapy with apatinib (250 mg orally every day) and camrelizumab (200 mg intravenously every 2 weeks). The patient continued to receive the same dose of 16 cycles of apatinib and camrelizumab after hepatectomy. By the time of this study, the patient has completed 18 months of follow-up, and no tumor recurrence or metastasis was found in tumor markers and imaging examinations. Apatinib in combination with camrelizumab is an effective therapy for the treatment of advanced hepatocellular carcinoma, and surgical resection after this conversion therapy may provide patients with long-term oncological benefits. However, this requires more samples to validate the conclusion.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1α After Treatment: A Cell Regulation Study

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.