Apatinib In Patients Research Articles

Establishment and validation of a population pharmacokinetic model for apatinib in patients with tumors

ObjectiveThis study aimed to develop a population pharmacokinetic (PPK) model for oral apatinib in Chinese oncology patients and investigate the factors influencing the pharmacokinetics of apatinib.MethodsWe gathered 199 blood concentration monitoring data points from 91 inpatient oncology participants receiving oral apatinib at the Third Affiliated Hospital of Soochow University. Covariates, such as age, gender, body weight, and indices of liver and renal function, were examined to assess their influence on the pharmacokinetic parameters of apatinib. The PPK model was developed using the nonlinear mixed-effects modeling procedure (NONMEM), and model validation was conducted using the bootstrap method and normalized prediction distribution error (NPDE) method.ResultsThe structural model adopted a one-compartment structure with first-order elimination. Notably, aspartate aminotransferase (AST) and the co-administered drug type emerged as primary covariates affecting apatinib clearance (CL/F). The finalized model was expressed as CL/F (L/h) = 56.7 × (AST/26.6)−0.298 × θ, when apatinib was combined with monoclonal antibodies, θ was 1; when combined with paclitaxel, θ was 0.58; when combined with other drugs (e.g., platinum, capecitabine, or the combination of tegafur, gimeracil, and oteracil potassium), θ was 1.60; When used as monotherapy, θ was 1.38. V/F = 674 L, and the absorption rate constant (Ka) was fixed at 0.08 h−1. Bootstrap results affirmed the model’s reliability and stability, while NPDE outcomes attested to the model’s fit.ConclusionOur study successfully established a PPK model for apatinib in oncology patients, revealing that liver function status and co-administered drug types significantly impacted apatinib CL/F. This finding underscored the potential necessity for dose adjustments to optimize efficacy, particularly in patients undergoing different chemotherapy regimens involving apatinib.

Efficacy and safety of camrelizumab plus apatinib in patients with advanced esophageal squamous cell carcinoma previously treated with immune checkpoint inhibitors (CAP 02 Re-challenge): A single-arm, phase II study

BackgroundWith the increasing use of immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC), there remains an unmet need for options to address disease progression after prior ICIs. This single-arm phase II study evaluated the efficacy and safety of re-challenge with camrelizumab plus apatinib in patients with advanced ESCC who were previously treated with ICIs. MethodsThis study enrolled patients aged 18–75 years with unresectable locally advanced, locally recurrent, or distant metastatic ESCC who received prior ICIs. Patients received intravenous camrelizumab 200 mg every 2 weeks and oral apatinib 250 mg daily until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was the investigator-assessed confirmed objective response rate (ORR). ResultsBetween September 1, 2021 and March 29, 2023, 49 eligible patients were enrolled and received treatment. Among the 49 patients, the confirmed ORR was 10.2 % (95 % CI 3.4–22.2), the disease control rate (DCR) was 69.4 % (54.6–81.7), the median progression-free survival (PFS) was 4.6 months (95 % CI 3.8–6.5) and overall survival (OS) was 7.5 months (5.5–13.6). Grade ≥ 3 treatment-related adverse events occurred in 17 patients (34.7 %). No treatment-related deaths occurred. ConclusionsThis study showed that the confirmed ORR was modest and did not reach clinically meaningful improvement for patients with ESCC who were previously treated with ICIs, with a manageable safety profile.

Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy (CAP 04): a single-arm phase II trial

BackgroundThe combination of anti-programmed death 1 (PD-1) inhibitors and tyrosine kinase inhibitors is an effective treatment strategy in endometrial cancer. We aimed to explore the efficacy and safety of camrelizumab plus apatinib as an alternative therapeutic option in patients with previously treated endometrial cancer.MethodsThis single-arm Simon’s two-stage phase II trial was conducted at the Fudan University Shanghai Cancer Center. Patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy were screened for potential participation. Eligible patients were treated with intravenous camrelizumab (200 mg d1 q2w) and oral apatinib (250 mg qd) every 4 weeks. The primary end point was the objective response rate (ORR) per RECIST v1.1 in the intention-to-treat principle.ResultsBetween January 20, 2020, and October 14, 2022, 36 patients (29 with microsatellite stability/mismatch repair proficient [MSS/pMMR] tumors; two with microsatellite instability-high/mismatch repair deficient [MSI-H/dMMR] tumors) were enrolled and treated. The confirmed ORR was 44.4% (95% CI: 27.9, 61.9) and the disease control rate was 91.7% (95% CI: 77.5, 98.2). The median duration of response was 9.3 (95% CI: 4.3, not reached) months, the median progression-free survival was 6.2 (95% CI: 5.3, 11.1) months, and the median overall survival was 21.0 (95% CI: 13.4, not reached) months during a median follow-up of 14.2 (interquartile range: 10.3, 27.6) months. Treatment-related adverse events of grade 3 or 4 occurred in 20 (55.6%) patients, with the most common being increased γ-glutamyl transferase (27.8%), alanine aminotransferase (16.7%) and aspartate aminotransferase (13.9%), and hypertension (11.1%). No treatment-related death occurred.ConclusionsCamrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy. The findings of this study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors.Trial registrationThis trial was retrospectively registered with ChiCTR.org.cn, number ChiCTR2000031932.

AB048. Evidence of effectiveness of neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas.

Recurrent high-grade glioma (HGG) is a challenge with limited treatment options and a poor prognosis. We conducted an open-label phase II study: neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas (NCT04588987), and interim analysis showed very promising results. We are further searching for evidence of the effectiveness of this strategy. Patients with recurrent HGG received neoadjuvant treatment with camrelizumab (intravenous injection 200 mg on day 1) and apatinib (oral 250 mg per day on days 1-7), and 14 days later received surgery for recurrent tumor resection. Sequential therapy began 2 weeks after surgery with the biweekly camrelizumab (200 mg) and 4 weeks after surgery with the daily apatinib (250 mg) until investigator assessed progressive disease or unable to tolerate toxicity. The primary endpoint was overall survival (OS). When patients suspected progress during per-protocol treatment, re-surgery for resection of lesion was done, and the tissue was further examined. Between October 9, 2020, and March 30, 2024, 24 patients were enrolled [19 glioblastomas, one World Health Organization (WHO) grade 4 diffuse astrocytoma, three anaplastic astrocytoma, and one anaplastic oligodendroglioma]. Nineteen patients with interim analysis data, and showed the median progression-free survival (PFS) was 4.8 months [95% confidence interval (CI): 4.4-5.2], the median OS was 12.9 months (95% CI: 9.3-16.4) respectively, with a median follow-up time of 17.5 months (95% CI: 9.0-26.1). There were two patients who suspected progress and received second surgery. One patient showed real tumor progression with active tumor cells. While another patient the histology revealed mainly necrosis with inflammatory cells. Five patients initially showed increased enhancement on magnetic resonance imaging (MRI) but without increased symptoms, and showed continuous improvement when receiving further treatment. This immuno-target combination neoadjuvant therapy in recurrent HGG demonstrated encouraging efficacy and revealed some evidence of efficacy, and worth to further investigate.

Single-arm study of camrelizumab plus apatinib for patients with advanced mucosal melanoma

BackgroundPrevious studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of...

Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II–III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2–4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3–48.1) in arm A and were 55.6% (95% CI 21.2–86.3) and 11.1% (95% CI 0.3–48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8–61.6) and 55.6% (95% CI 21.2–86.3). With a median follow-up of 22.4 months (95% CI 19.0–26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

Camrelizumab combined with apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: A phase 2 trial.

e16087 Background: Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of PD-1 inhibitors combined with angiogenesis inhibitors in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab (PD-1 inhibitor) plus chemotherapy or apatinib (angiogenesis inhibitor) as neoadjuvant therapy for locally advanced ESCC. Methods: This was an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0-3M0 ESCC. Eligible patients were 18-75 years old, had ECOG PS score of 0-1. Patients received 2 cycles (1 cycle per 4 weeks) of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Feb 2022 and Dec 2023, 24 patients (19 males and 5 females) with a median age of 67 years were enrolled in the study. Twenty-one patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 95%. Nineteen patients completed surgery and all patients (100%) reached R0 resection, 3 patients (3/19, 10.5%) reached pCR, 8 patients (8/19, 42.1%) reached MPR, and 13 patients (13/19, 68.4%) had TNM downstaging. The median follow-up was 11.9 months, and the median DFS had not yet reached. Any grade and grade ≥3 adverse events occurred in 87.5% and 8.3% of 24 patients, respectively. The most common AEs were increased alanine aminotransferase (8/24, 33.3%), increased alanine aminotransferase (7/24, 29.2%) and thrombocytopenia(7/24, 29.2%). No new safety signals or treatment-related deaths were observed. Conclusions: Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03917966 .

Camrelizumab plus apatinib after progression on immune checkpoint inhibitors in patients with advanced esophageal squamous cell carcinoma (CAP 02 Re-challenge): A single-arm multicenter, phase II trial.

364 Background: The optimal therapies for patients with advanced esophageal squamous cell carcinoma (ESCC) who have progressed after immune checkpoint inhibitors (ICIs) are unclear. This phase II single-arm study aimed to assess the efficacy and safety of re-challenge with camrelizumab plus apatinib in this population. Methods: This study enrolled patients with unresectable locally advanced, locally recurrent, or metastatic ESCC who had experienced prior progression on ICI treatment. Enrolled patients received camrelizumab 200 mg intravenously every two weeks along with daily oral apatinib 250 mg. Treatment continued until disease progression, unacceptable toxicity, or patient withdrawal of consent. The primary endpoint was the confirmed objective response rate (ORR). Secondary endpoints included disease control rate (DCR), duration of response (DOR), time to response (TOR), progression-free survival (PFS), overall survival (OS), 3- and 6-month PFS rates, 6-, 9- and 12-month OS rates, and safety. Results: From September 1, 2021, to March 29, 2023, 49 eligible patients were enrolled and given treatment. Among 38 treated patients who had at least one post-baseline efficacy measurement, the ORR and confirmed ORR were 36.8% (95% CI 21.8–54.0) and 13.2% (95% CI 4.4–28.1); the DCR was 89.5% (95% CI 75.2–97.1); the median DOR was 3.0 months; and the median TOR was 2.2 months. Among the 49 treated patients, the median PFS was 4.6 months (95% CI 3.8–6.5) and OS was 7.5 months (95% CI 5.5–13.6). Patients who were both PD-L1 positive and had responded to previous ICI therapy had the longest median PFS (5.7 months, 95% CI 3.9–not reached) and OS (9.6 months, 95% CI 7.5–not reached). Grade ≥ 3 treatment-related adverse events occurred in 34.7% of patients (17/49). Conclusions: This study showed promising efficacy and an acceptable safety profile of camrelizumab plus apatinib for patients with advanced ESCC who had progressed after ICI therapy. The subset of patients who were both PD-L1 positive and had a prior ICI response seemed to benefit most. Clinical trial information: NCT03736863 .

A pilot study of multi-antigen stimulated cell therapy-I plus camrelizumab and apatinib in patients with advanced bone and soft-tissue sarcomas

BackgroundCell-based immunotherapy shows the therapeutic potential in sarcomas, in addition to angiogenesis-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI). Multi-antigen stimulated cell therapy-I (MASCT-I) technology is a sequential immune cell therapy for cancer, which composes of multiple antigen-loaded dendritic cell (DC) vaccines followed by the adoptive transfer of anti-tumor effector T-cells.MethodsIn this phase 1 study, we assessed MASCT-I plus camrelizumab (an ICI against PD-1) and apatinib (a highly selective TKI targeting VEGFR2) in patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma after at least one line of prior systemic therapy. One MASCT-I course consisted of 3 DC subcutaneous injections, followed by 3 active T cell infusions administered 18–27 days after each DC injection. In schedule-I group, 3 DC injections were administered with a 28-day interval in all courses; in schedule-II group, 3 DC injections were administered with a 7-day interval in the first course and with a 28-day interval thereafter. All patients received intravenous camrelizumab 200 mg every 3 weeks and oral apatinib 250 mg daily.ResultsFrom October 30, 2019, to August 12, 2021, 19 patients were enrolled and randomly assigned to schedule-I group (n = 9) and schedule-II group (n = 10). Of the 19 patients, 11 (57.9%) experienced grade 3 or 4 treatment-related adverse events. No treatment-related deaths occurred. Patients in schedule-II group showed similar objective response rate (ORR) with those in schedule-I group (30.0% versus 33.3%) but had higher disease control rate (DCR; 90.0% versus 44.4%) and longer median progression-free survival (PFS; 7.7 versus 4.0 months). For the 13 patients with soft-tissue sarcomas, the ORR was 30.8%, DCR was 76.9%, and median PFS was 12.9 months; for the 6 patients with osteosarcomas, the ORR was 33.3%, the DCR was 50.0%, and median PFS was 5.7 months.ConclusionsOverall, MASCT-I plus camrelizumab and apatinib was safe and showed encouraging efficacy in advanced bone and soft-tissue sarcoma, and schedule-II administration method was recommended.Trial registrationClinicalTrials.gov, NCT04074564.

1296P Neoadjuvant camrelizumab and apatinib in patients with resectable non-small-cell lung cancer: One-year update from a phase II trial

1296P Neoadjuvant camrelizumab and apatinib in patients with resectable non-small-cell lung cancer: One-year update from a phase II trial

487. CAMRELIZUMAB COMBINED WITH CHEMOTHERAPY OR APATINIB AS NEOADJUVANT THERAPY FOR LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A PHASE 2 TRIAL

Abstract Background Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of camrelizumab (PD-1 inhibitor) combined with apatinib (angiogenesis inhibitor) in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab plus chemotherapy or apatinib as neoadjuvant therapy for locally advanced ESCC. Here, we reported the results of cohort 2. Methods This is an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0–3 M0 ESCC. Eligible patients were 18–75 years old, had ECOG PS score of 0–1. Cohort 2 planned to enroll patients with 4 cycles of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4–6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival, overall survival, and safety. Results Between Feb 2022 and May 2023, 21 patients were enrolled in cohort 2. 14 patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 100%. 14 patients completed surgery and all patients (100%) reached R0 resection, 4 patients (4/14, 28.6%) reached MPR, 2 patients (2/14, 14.3%) reaching pCR, and 9 patients (9/14, 64.3%) had TNM downstaging. Any grade and grade ≥ 3 adverse events occurred in 84.2% and 9.5% of 21 patients, respectively. The most common AEs were thrombocytopenia (6/21, 28.6%) and increased alanine aminotransferase (6/21, 28.6%). No new safety signals or treatment-related deaths were observed. Conclusions Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future.

Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.

Efficacy and Safety of Stereotactic Body Radiotherapy Combined with Camrelizumab and Apatinib in Patients with Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

This study aimed to evaluate the efficacy and safety of camrelizumab plus apatinib with or without stereotactic body radiotherapy (SBRT) as first-line therapy for patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). This is a multicenter, open-label, noncomparative, randomized trial that recruited patients with HCC with type II/III/IV PVTT, who had not previously received systemic therapy. Patients were randomly assigned (2:1) to receive camrelizumab (200 mg, every 3 weeks) and apatinib (250 mg, every day) with or without SBRT [95% planning target volume (PTV), 36-40 Gy/6-8 Gy]. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response, time to progression, and safety. Sixty patients were enrolled and randomly assigned to two prospective cohorts. Median OS were 12.7 months [95% confidence interval (CI), 10.2-not available (NA)] and 8.6 months (95% CI, 5.6-NA), and median PFS were 4.6 months (95% CI, 3.3-7.0) and 2.5 months (95% CI, 2.0-7.6) for the SBRT and non-SBRT cohorts, respectively. The ORR and DCR were 47.5% and 72.5% in the SBRT cohort, and 20.0% and 40.0% in the non-SBRT cohort. The most common treatment-related adverse events of any grade were hypertension (55.0%), hand-foot syndrome (51.7%), and leukopenia (50.0%). Grade ≥ 3 was reported in 13 (21.7%) patients. First-line treatment with camrelizumab-apatinib combined with or without SBRT showed clinical benefits in patients with HCC with PVTT, with an acceptable safety profile. Thus, these combination regimens may be potential options for such patients.

Efficacy and Safety of Apatinib in Patients with Recurrent Glioblastoma.

Glioblastoma is a cranial malignant tumor with a high recurrence rate after surgery and a poor response to chemoradiotherapy. Bevacizumab has demonstrated efficacy in the treatment of glioblastoma by inhibiting vascular endothelial growth factor, but the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors varies in treating glioblastoma. This single-arm prospective study aimed to explore the efficacy and safety of the vascular endothelial growth factor receptor tyrosine kinase inhibitor apatinib in treating recurrent glioblastoma after chemoradiotherapy. A total of 15 patients with recurrent glioblastoma (2016 World Health Organization grade IV) after chemoradiotherapy were enrolled in this study from September 2017 to September 2019 and treated with apatinib 500 mg once daily. Responses were evaluated according to the Response Assessment in Neuro-Oncology criteria, and adverse events were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. The overall response rate was 33.3%, and the disease control rate was 66.6%. The median progression-free survival was 2months, and the median overall survival was 6.5months. The apatinib dose was adjusted in seven patients because of adverse events (46.6%). The most common adverse events were thrombocytopenia (53.3%), asthenia (40%), and hand-foot syndrome (33.3%). Apatinib might be effective in treating recurrent glioblastoma after chemoradiotherapy in terms of the overall response rate, but the efficacy is not durable and the clinical benefit is limited. The adverse effects of apatinib were acceptable. ChiCTR-ONC-17013098, date of registration: 24 October, 2017.

Real-world efficacy and safety of TACE plus camrelizumab and apatinib in patients with HCC (CHANCE2211): a propensity score matching study

ObjectivesThis study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting.MethodsA total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy.ResultsAfter propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26–0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37–0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively.ConclusionsTACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC.Clinical relevance statementCompared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events.Key Points• This propensity score–matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC.• Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.

Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy: A single-arm phase II trial.

5516 Background: The first stage results of a Simon’s two-stage single-arm phase II trial showed promising antitumor activity and manageable safety of camrelizumab (a humanized anti-PD-1 monoclonal antibody) plus apatinib (a highly selective VEGFR2 inhibitor) in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy. Here, we report the primary results of this trial. Methods: This open-label, single-arm, phase II trial used a minimax Simon’s two-stage design. Patients with advanced or recurrent endometrial cancer that had progressed after at least one prior systemic therapy were treated with camrelizumab (200 mg, intravenously, every two weeks) and apatinib (250 mg, orally, daily) on a four-week cycle until disease progression or intolerable toxicity. The primary endpoint was the objective response rate per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other assessed endpoints were disease control rate, time to response, duration of response, time to treatment failure, progression-free survival, overall survival, and treatment-related adverse events. Results: Between January 20, 2020 and October 14, 2022, 36 patients (median age: 60 [range: 29, 76] years; 17 [47.2%] had Eastern Cooperative Oncology Group [ECOG] performance status 1; 15 [41.7%] had received at least two prior systemic therapies) were enrolled. At the date of data cutoff (December 31, 2022), the median follow-up time was 13.9 (interquartile range: 5.8-23.2) months. All 36 patients were evaluable for efficacy, the confirmed objective response rate was 44.4% (95% CI: 27.9%, 61.9%) and the conformed disease control rate was 88.9% (95% CI: 73.9%, 96.9%), with two complete response, 14 partial response, and 16 stable disease. The median progression-free survival was 6.4 (95% CI: 5.2, 13.0) months. The treatment-related adverse events of grade 3 or greater occurred in 19 (52.8%) patients, with increased gamma-glutamyltransferase (8 [22.2%]), hyperglycemia (4 [11.1%]), hypertension (4 [11.1%]) and increased direct bilirubin (4 [11.1%]) being most common. Reactive cutaneous capillary endothelial proliferation occurred in 6 (16.7%) patients and all were grade 1 or 2. No treatment-related death occurred. Conclusions: Camrelizumab plus apatinib show promising antitumor activity and manageable toxicity in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy and warrant further investigation. Clinical trial information: ChiCTR2000031932 .

A retrospective cohort study examining the effects of anti–PD-1 antibody in combination with apatinib in patients previously treated for HER2-negative advanced gastric/gastroesophageal junction cancer.

e16048 Background: Combining immune checkpoint inhibitors with vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors are effective in treating a number of solid tumors; however, evidence in advanced gastric/gastroesophageal junction (G/GEJ) cancer is limited. Methods: This retrospective study included consecutive patients who received a programmed cell death protein 1 (PD-1) inhibitor plus the VEGFR-2 inhibitor apatinib, second-line or later to treat unresectable advanced or metastatic, histologically-proven, human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer in a single center between November 1, 2018 and March 31, 2021. Treatment was continued until the disease progressed or the toxicity became intolerable. Results: Data from 52 patients (median age 64 years; 38 men) were analyzed. The primary tumor site was the stomach in 29 patients (56%) and the GEJ in 23 patients (44%). The number of previous line(s) of therapy was one in 22 patients (42%) and two or more in 30 patients (58%). Liver metastasis was present in 22 patients (42%) and 33 patients (63%) had two or more metastatic sites. PD-1 inhibitors taken included camrelizumab (n=28), sintilimab (n=18), pembrolizumab (n=3) and tislelizumab (n=1), all given 200 mg every 3 weeks (Q3W), and toripalimab (240 mg Q3W) and nivolumab (200 mg every 2 weeks) in 1 patient each. The objective response rate was 15.4% (95% confidence interval [CI] 6.9–28.1), the disease control rate was 61.5% (95% CI 47.0–74.7). After a median follow-up of 14.8 months (range 11.8–23.5), median progression-free survival was 4.2 months (95% CI 2.6–4.8), overall survival was 9.3 months (95% CI 7.9–12.9). Grade 3–4 treatment-related adverse events occurred in 12 patients (23.1%). There was no unexpected toxicity or death. Conclusions: Combination therapy with an anti-PD-1 antibody and apatinib was effective in patients with previously treated, unresectable advanced or metastatic G/GEJ cancer, with a manageable safety profile.

Efficacy and safety of apatinib combined with radiotherapy in the treatment of advanced pancreatic cancer: a meta-analysis

ObjectiveAt present, pancreatic cancer (PC) has a high morbidity and mortality rate and a poor prognosis. The aim of this article was to study the efficacy and safety of apatinib combined with radiotherapy in the treatment of advanced PC.MethodsThe PubMed, Cochrane Library, Embase, Wanfang, CNKI, VIP, and CBM databases were searched by computer to identify studies on the application of apatinib in patients with advanced PC. The patients in the included study were divided into an observation group (apatinib combined with radiotherapy) and a control group (radiotherapy only), and meta-analysis was performed for each outcome with Revman 5.4 software. This study was successfully registered on the PROSPERO website, and the registration number is CRD: 42,022,384,056 (available at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384056).ResultsA total of 7 randomized controlled trials (RCTs) with 428 patients were included, including 215 in the observation group and 213 in the control group. Compared with the control group, the observation group showed a greater objective response rate [OR = 3.26, 95% CI (2.18, 4.87), P < 0.0001], disease control rate [OR = 5.04, 95% CI (3.12, 8.12), P < 0.0001], complete response rate [OR = 3.87, 95% CI (1.51, 9.88), P = 0.005], and partial response rate [OR = 2.43, 95% CI (1.63, 3.61), P < 0.001], The 1-year survival rate [OR = 2.39, 95% CI (1.15, 4.96), P < 0.05], 2-year survival rate [OR = 2.41, 95% CI (1.03, 5.61), P < 0.05], progression-free survival time [MD = 1.17, 95% CI (0.37, 1.96), P < 0.05], overall survival time [MD = 1.47, 95% CI (0.13, 2.80), P < 0.05], while the stability rate [OR = 1.14, 95% CI (0.72, 1.81), P = 0.58] and various complications were not significantly different between the two groups.ConclusionApatinib combined with radiotherapy was more effective than radiotherapy alone in the treatment of advanced pancreatic cancer (PC), and apatinib had acceptable safety. However, since our study was limited by the quantity and quality of the included studies, we look forward to more large-sample, multicentre, and high-quality RCTs in the future to verify the conclusions.

Safety and efficacy of apatinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma after the failure of two or more lines of chemotherapy (AHEAD): a prospective, single-arm, multicenter, phase IV study

BackgroundApatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings.MethodsPatients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan–Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method.ResultsBetween May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6–5.4%), and DCR was 35.8% (95% CI, 33.7–38.0%). The median PFS was 2.7 months (95% CI 2.2–2.8), and the median OS was 5.8 months (95% CI 5.4–6.1).ConclusionsThe findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment.Trial registrationThis study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

A Retrospective Cohort Study Examining the Effects of Anti-PD-1 Antibody in Combination with Apatinib in Patients Previously Treated for Her2-Negative Advanced Gastric/Gastroesophageal Junction Cancer.

Combining immune checkpoint inhibitors with vascular endothelial growth factor/vascular endothelial growth factor receptor inhibitors is effective in treating a number of solid tumors; however, evidence in advanced gastric/gastroesophageal junction (G/GEJ) cancer is limited. This retrospective study included consecutive patients who received a programmed cell death protein 1 (PD-1) inhibitor plus the vascular endothelial growth factor receptor 2 inhibitor apatinib, second-line or later to treat unresectable advanced or metastatic, histologically proven, human epidermal growth factor receptor 2-negative G/GEJ cancer in a single center between November 1, 2018, and March 31, 2021. Treatment was continued until the disease progressed or the toxicity became intolerable. We examined data from 52 patients. The primary tumor site was the stomach in 29 patients and the GEJ in 23 patients. PD-1 inhibitors administered included camrelizumab (n=28), sintilimab (n=18), pembrolizumab (n=3), and tislelizumab (n=1), and all patients were given 200mg every 3weeks, and toripalimab (240mg every 3weeks) and nivolumab (200mg every 2weeks) were given to 1 patient each. For 28days, apatinib 250mg was administered orally once a day. The objective response rate was 15.4% (95% confidence interval [CI], 6.9-28.1), and the disease control rate was 61.5% (95%CI, 47.0-74.7). After 14.8months of median follow-up, the median progression-free survival was 4.2months (95%CI, 2.6-4.8), and the overall survival was 9.3months (95%CI, 7.9-12.9). Twelve patients underwent grade 3-4 treatment-related adverse events (23.1%). There was no unexpected toxicity or death. This trial demonstrated combination therapy with an anti-PD-1 antibody and apatinib was effective and safe in patients with previously treated unresectable advanced or metastatic G/GEJ cancer.