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First-line treatment of apatinib in elderly patient of advanced gastric carcinoma: A case report of NGS-driven targeted therapy.

ABSTRACT: Gastric carcinoma (GC) is a common gastrointestinal malignancy with high incidence and mortality worldwide, and most patients are diagnosed in the late stages of disease. Palliative chemotherapy provides a survival benefit for patients with inoperable advanced GC. However, elderly patients who are unable to tolerate chemotherapy had worse prognosis due to lack of effective treatment. Herein we reported a Chinese elderly GC patient using next generation sequencing (NGS)-based tumor DNA analysis. Valuable gene variants of vascular endothelial growth factor (VEGF) A gene amplification were detected. Additionally, a novel NOTCH1-BPHL fusion has been identified. He received antiangiogenic drug apatinib and showed both good clinical and radiographic response, but eventually died of non-cancer related cause, with progression free survival time (PFS) and overall survival time (OS) up to 9.53 months. This was the first GC case with apatinib usage as first-line treatment under the guidance of NGS gene profiling.

SUBMITTER: Yang Y

PROVIDER: S-EPMC5915029 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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First-line treatment of apatinib in elderly patient of advanced gastric carcinoma: A case report of NGS-driven targeted therapy.

Yang Yan Y Zhang Wuqiong W Yao Jinghao J Liu Jing J Qin Shukui S Wu Qiong Q

Cancer biology & therapy 20180222 5

Gastric carcinoma (GC) is a common gastrointestinal malignancy with high incidence and mortality worldwide, and most patients are diagnosed in the late stages of disease. Palliative chemotherapy provides a survival benefit for patients with inoperable advanced GC. However, elderly patients who are unable to tolerate chemotherapy had worse prognosis due to lack of effective treatment. Herein we reported a Chinese elderly GC patient using next generation sequencing (NGS)-based tumor DNA analysis. ...[more]

PMID: 29336669

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Project description:Lessons learnedApatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced gastric cancer. There was a tendency for patients with lymph node metastasis to have prolonged median progression-free survival and median overall survival, compared with patients with liver metastasis.BackgroundThe best choice of first-line chemotherapy regimen for patients with metastatic gastric cancer is still debated. We combined apatinib and S-1 as a new first-line therapy to treat advanced gastric cancer. The efficacy and safety of the combination were assessed, with the goal of determining the most appropriate subgroup of patients who could benefit from this new regimen.MethodsThis study was an open, exploratory single-arm, phase II trial. Enrolled patients received apatinib plus S-1 treatment (apatinib, 500 mg, once a day [qd], days 1-21; S-1, 40 mg/m2 , bid, days 1-14). The primary endpoints were progression-free survival (PFS) and safety of this new regimen. Next-generation sequencing was used to explore potential biomarkers.ResultsA total of 30 patients were enrolled. The median progression-free survival (mPFS) was 4.21 months (95% confidence interval [CI], 2.29-6.13 months). The median overall survival (mOS) was 7.49 months (95% CI, 4.81-10.17 months). Patients with lymph node metastasis had prolonged mPFS and mOS when compared with those with liver metastasis (mPFS, 4.21 vs. 1.84 months; mOS, 8.21 vs. 6.31 months, p = .08). The most common grade 3 to 4 adverse events were abdominal pain, dizziness, and diarrhea. Gene mutation profiles between the two subgroups were significantly different.ConclusionApatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced gastric cancer. Toxicity was consistent with known profiles when given as monotherapy. There was a tendency toward prolonged mPFS and mOS in patients with lymph node metastasis compared with patients with liver metastasis, which could support the need to design a future clinical trial with a better defined patient population.

Project description:The retrospective study was conducted to evaluate the efficacy and safety of careful dose modification of apatinib as third or further-line treatment in advanced gastric cancer (aGC) patients with poor performance status (PS = 2 or 3).Patients with aGC of poor PS who had received at least 2 lines of chemotherapy were treated with apatinib at a dose of 250 mg initially and best supportive care (BSC). During the whole treatment, the dose of apatinib was adjusted according to the status of PS (group treatment). Meanwhile, patients of poor PS (PS = 2 or 3) with aGC who received BSC alone after second or further-line treatment in the recent 5 years in our institution have been investigated for their median overall survival (mOS) as control. Kaplan-Meier curve was adopted for the description of OS in the 2 groups. Univariate analysis was conducted with log-rank test between OS and the potential characteristics including gender, age, PS status, primary tumor lesion, Her-2 status, and previous lines of treatment. Toxicities were assessed with the criteria of National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.0.A total of 23 patients who received apatinib plus BSC treatment and 41 patients treated with BSC alone were reviewed in the present study. Median exposure time of apatinib was 2.4 months ranging from 0.2 to 5.1 months. The median OS in the group treatment was 4.3 months (95% CI, 2.735-5.865) comparing to the control as 2.1 months (95% CI, 1.473-2.727, P = .0004). In addition, PS status was shown as the only independently significant factor to influence the OS (P = .049). Fatigue (82.6%), appetite decrease (73.9%), and anemia (69.6%) appeared to be the most common adverse events at any grade during the therapy of apatinib.The outcomes of the present study revealed that therapeutic model of careful dose modification of apatinib therapy initiated with low dose plus BSC as third or further-line treatment might be more beneficial on survival time comparing to BSC alone in patients with aGC of poor PS, however, as well as apparent adverse events.

Dataset Information

First-line treatment of apatinib in elderly patient of advanced gastric carcinoma: A case report of NGS-driven targeted therapy.

Publications

First-line treatment of apatinib in elderly patient of advanced gastric carcinoma: A case report of NGS-driven targeted therapy.

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