Frontiers in Oncology
As a novel small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), Methylsulfonic apatinib (apatinib) exhibits a specific antitumor effect in various solid tumors via inhibition of angiogenesis. The present study was performed to evaluate the clinical efficacy and safety of apatinib in the treatment of advanced cholangiocarcinoma after failed gemcitabine-based chemotherapy.
This was a prospective open-label phase II trial (NCT03521219). A total of 32 patients, in whom gemcitabine-based first-line chemotherapy for advanced intrahepatic cholangiocarcinoma had failed, were consecutively enrolled in a prospective, open, exploratory, and single-center clinical trial from November 2017 to November 2018. They were treated with apatinib mesylate second-line monotherapy (orally, 500 mg per day for a cycle of 28 days) until progressive disease or unacceptable toxicity. Using Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST 1.1) and the Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE 4.0), the efficacy and adverse were evaluated, respectively. Kaplan-Meier method was used for survival analysis.
Twenty-six patients were enrolled in full analysis set. At the end of follow-up, two patients were lost to follow-up, 24 of 26 patients in FAS were included in efficacy analyses. For the efficacy analysis set, the objective response rate (ORR) was 20.8% [95% confidence interval (CI): 9.24–40.47%] and the disease control rate (DCR) was 62.5% (95% CI: 112.86–387.14 days). One patient (4%) showed complete response (CR), 4 patients (17%) showed partial response (PR), 10 patients (41.7%) stable disease (SD), and 9 patients (37.5%) had progressive disease (PD). Meanwhile, apatinib therapy achieved the median progression-free survival PFS was 95 days (95% CI: 79.70–154.34 days), and the median OS was 250 days (95% CI: 112.86–387.14 days). Furthermore, univariate analysis revealed that age and tumor’s anatomic location significantly affected PFS (P < 0.05). The most common clinically adverse events (AEs) included myelosuppression (69.2%), hypertension (57.7%), proteinuria (46.2%). The AEs were mild, mainly in grade 1 or 2, and no toxicity-induced death occurred.
Apatinib monotherapy is an effective and promising regimen for treating patients with advanced cholangiocarcinoma who experienced failure of gemcitabine-based chemotherapy.
Text reproduced verbatim from publisher (source); DOI; CC-BY-4.0.
Ge Zhang, Shuai Gong, Lina Pang, Lixia Hou, Wei He. Efficacy and Safety of Apatinib Treatment for Advanced Cholangiocarcinoma After Failed Gemcitabine-Based Chemotherapy: An Open-Label Phase II Prospective Study. Frontiers in Oncology. 2021;11:659217. https://doi.org/10.3389/fonc.2021.659217
Efficacy and Safety of Apatinib Treatment for Advanced Cholangiocarcinoma After Failed Gemcitabine-Based Chemotherapy: An Open-Label Phase II Prospective Study
A small prospective single-arm study reported apatinib tumor-response, survival and toxicity observations. Enrollment, safety and efficacy denominators differ; the activity signal and descriptive safety findings do not establish comparative superiority or a general treatment recommendation.
What tumor-response, survival and toxicity observations were reported in this prospective single-arm study after gemcitabine-based treatment failure in advanced cholangiocarcinoma?
This is human prospective treatment evidence from a small single-arm study, not a randomized comparison. Enrolled, treated and efficacy populations differ. Reported responses and adverse events support a clinical activity signal and descriptive safety assessment, but do not establish superiority or a general treatment recommendation.
The unique total of 32 is enrollment only, not the response-rate denominator. Enrollment, treated and efficacy populations overlap and must not be added together.
| Measure | Value |
|---|---|
| enrolled | 32 |
| withdrew before treatment | 6 |
| FAS safety population | 26 |
| efficacy population | 24 |
Source locator: Results: Patients' Characteristics; Efficacy of Apatinib Treatment
These are observations without a concurrent control. ORR uses the reported percentage interval; DCR uses the Results-reported percentage interval, not the survival-day interval printed in the abstract.
| Measure | Value |
|---|---|
| efficacy denominator | 24 |
| CR | 1 |
| PR | 4 |
| SD | 10 |
| PD | 9 |
| ORR | 20.8% |
| ORR reported 95 percent CI | 9.24–40.47% |
| DCR | 62.5% |
| DCR Results reported 95 percent CI | 42.71–78.84% |
Source locator: Results: Efficacy of Apatinib Treatment
Without a concurrent comparison, these observed survival times do not establish a survival gain or comparative benefit.
| Measure | Value |
|---|---|
| median PFS | 95 days |
| PFS reported 95 percent CI | 79.70–154.34 days |
| median OS | 250 days |
| OS reported 95 percent CI | 112.86–387.14 days |
Source locator: Results: Efficacy of Apatinib Treatment; Fig. 1
No Grade 4 events or drug-related deaths were reported. Adverse-event categories overlap and cannot be summed as independent patients; absence of observed events in a small sample does not establish absence of risk.
| Measure | Value |
|---|---|
| safety denominator | 26 |
| myelosuppression | 69.2% |
| hypertension | 57.7% |
| proteinuria | 46.2% |
| Grade 3 hypertension | 3 patients |
| Grade 3 leukopenia | 3 patients |
| Grade 4 or drug related deaths | Not reported |
Source locator: Results: Safety; Table 3
| Cohort | Role | n | Relationship |
|---|---|---|---|
| Enrolled cohort — not the efficacy denominator | Enrollment total; treated/FAS and efficacy denominators are specified in KF1. | 32 | Independent cohort |
Enrollment was 32, FAS/safety 26 and efficacy 24 after six pretreatment withdrawals. In the efficacy population, CR 1/PR 4/SD 10/PD 9 gave reported ORR 20.8% (95% CI 9.24–40.47%) and DCR 62.5% (Results-reported 95% CI 42.71–78.84%), without a concurrent control.
The efficacy denominator was 24, not all 32 enrolled patients: ORR 20.8% (reported 95% CI 9.24–40.47%) and DCR 62.5% (Results-reported 95% CI 42.71–78.84%). The DCR interval is attributed to Results, not the abstract survival-day interval.
Median PFS was 95 days (reported 95% CI 79.70–154.34 days) and OS 250 days (reported 95% CI 112.86–387.14 days). These are observations, not a demonstrated comparative survival gain.
Evidence: KF3
With safety n=26, myelosuppression 69.2%, hypertension 57.7% and proteinuria 46.2% were reported. Grade 3 hypertension and leukopenia each affected three patients; no Grade 4 events or drug-related deaths were reported. Overlapping categories and limited sample size prevent a no-risk inference.
Evidence: KF4
| Row ID | Component | Context | Finding | Evidence Level | Scope | Source Locator | Evidence refs |
|---|---|---|---|---|---|---|---|
| evidence-apatinib-1 | Enrollment and overlapping analysis populations | The unique total of 32 is enrollment only, not the response-rate denominator. Enrollment, treated and efficacy populations overlap and must not be added together. | Thirty-two patients enrolled; six withdrew before treatment, leaving 26 in the FAS/safety population and 24 in the efficacy analysis. | Human interventional activity and descriptive safety evidence without a concurrent control | Keeps enrollment distinct from overlapping safety and efficacy denominators. | Results: Patients' Characteristics; Efficacy of Apatinib Treatment | KF1 |
| evidence-apatinib-2 | Tumor-response and disease-control observations | These are observations without a concurrent control. ORR uses the reported percentage interval; DCR uses the Results-reported percentage interval, not the survival-day interval printed in the abstract. | Among 24 efficacy-evaluable patients, responses were CR 1, PR 4, SD 10 and PD 9; ORR was 20.8% and DCR was 62.5%. | Human interventional activity and descriptive safety evidence without a concurrent control | Supports a single-arm activity signal with an efficacy denominator of 24; it does not establish superiority. | Results: Efficacy of Apatinib Treatment | KF2 |
| evidence-apatinib-3 | Progression-free and overall survival observations | Without a concurrent comparison, these observed survival times do not establish a survival gain or comparative benefit. | Median PFS was 95 days (reported 95% CI 79.70–154.34 days), and median OS was 250 days (reported 95% CI 112.86–387.14 days). | Human interventional activity and descriptive safety evidence without a concurrent control | Describes observed survival without attributing a comparative treatment gain. | Results: Efficacy of Apatinib Treatment; Fig. 1 | KF3 |
| evidence-apatinib-4 | Treated-population adverse events | No Grade 4 events or drug-related deaths were reported. Adverse-event categories overlap and cannot be summed as independent patients; absence of observed events in a small sample does not establish absence of risk. | In the safety population of 26, myelosuppression, hypertension and proteinuria were reported in 69.2%, 57.7% and 46.2%; Grade 3 hypertension and leukopenia each occurred in three patients. | Human interventional activity and descriptive safety evidence without a concurrent control | Describes reported toxicity including Grade 3 events, not absence of treatment risk. | Results: Safety; Table 3 | KF4 |
Thirty-two patients enrolled; six withdrew before treatment, leaving 26 in the FAS/safety population and 24 in the efficacy analysis. The unique total of 32 is enrollment only, not the response-rate denominator. Enrollment, treated and efficacy populations overlap and must not be added together.
Evidence: KF1
Among 24 efficacy-evaluable patients, responses were CR 1, PR 4, SD 10 and PD 9; ORR was 20.8% and DCR was 62.5%. These are observations without a concurrent control. ORR uses the reported percentage interval; DCR uses the Results-reported percentage interval, not the survival-day interval printed in the abstract.
Evidence: KF2
Median PFS was 95 days (reported 95% CI 79.70–154.34 days), and median OS was 250 days (reported 95% CI 112.86–387.14 days). Without a concurrent comparison, these observed survival times do not establish a survival gain or comparative benefit.
Evidence: KF3
In the safety population of 26, myelosuppression, hypertension and proteinuria were reported in 69.2%, 57.7% and 46.2%; Grade 3 hypertension and leukopenia each occurred in three patients. No Grade 4 events or drug-related deaths were reported. Adverse-event categories overlap and cannot be summed as independent patients; absence of observed events in a small sample does not establish absence of risk.
Evidence: KF4
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