Advanced Gastric Cancer In China Research Articles

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Advances in translational therapy for locally advanced gastric cancer

Translational therapy refers to a combination of chemotherapy, radiotherapy, targeted therapy, and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection. This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection, thus enabling the patients to prolong their survival time and improve their quality of life. In gastric cancer, translational therapy has been tried and improved. At present, there are a large number of patients with locally advanced gastric cancer in China, and the selection of suitable patients for translational therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.

The efficacy and adverse reactions of DCF and FOLFOXs regimens for patients with advanced gastric cancer in China: a meta-analysis

BackgroundGastric cancer is a malignant tumor originating from the gastric mucosal epithelium, ranking fourth in the incidence of male malignant tumors and third in mortality rate. The aim of this study is to investigate the efficacy and adverse reactions of DCF and FOLFOXs regimens in the treatment of advanced gastric cancer.MethodsRelevant prospective clinical controlled studies were retrieved from WanFang Data, CBM, CNKI, PubMed, The Cochrane Library and Embase databases and meta-analysis was performed using RevMan 5.3 software.ResultsThe effective rates of DCF group and FOLFOXs group were basically the same (RR 1.06, 95% CI: 0.92–1.23, P=0.41). The incidence of nausea and vomiting (RR 1.36, 95% CI: 1.15–1.60), anemia (RR 2.04, 95% CI: 1.55–2.68), thrombocytopenia (RR 1.52, 95% CI: 1.15–2.01) and leukopenia (RR 1.70, 95% CI: 1.44–2.01) with FOLFOXs regimen were significantly lower than DCF regimen, while the incidence of sensory neurotoxicity was significantly higher than DCF regimen (RR 0.53, 95% CI: 0.38–0.74). There were no significant differences in efficacy, ORR and DCR between different doses in the FOLFOXs group (P=0.233).ConclusionsThe efficacy of FOLFOXs regimen was comparable to that of DCF regimen in the treatment of advanced gastric cancer, but the incidence of adverse reactions was significantly lower, and there were no significant differences between different therapeutic doses.

Real-world observation of the efficacy and prognostic factors analysis of apatinib for patients with advanced gastric cancer.

e15508 Background: Apatinib is the first oral anti-angiogenic agent approved for the treatment of advanced gastric cancer in China. With the development of marketing promotion, the real world observation of the efficacy and prognostic factors analysis of apatinib become the urgent need for clinical decision. The aim of this study is to evaluate the efficacy and safety of apatinib in patients with advanced gastric cancer, and the association between some prognostic factors and clinical outcomes. Methods: We collected the data of 153 patients with advanced gastric cancer, who were treated with apatinib after failure of at least one regimen chemotherapy from December 2014 to June 2019. Treatment response, progression-free survival(PFS), overall survival(OS) and treatment-related adverse events were evaluated. Results: The median PFS for 153 patients was 3.1m (95% confidence interval, CI 2.863-3.337). The median OS was 6.0m (95% CI 4.392-7.608). Adverse events of grade 3 or above happened in 47.6 percent of patients and 61.7 percent of whom stopped treatment. Multivariate analysis showed that the number of metastatic sites was the independent factor simultaneously predicting DCR (disease control rate, P = 0.008) and OS (P = 0.007). Patients spending more than one year from diagnosis to treatment with apatinib had better DCR (P = 0.032) and longer PFS (P = 0.015). Liver metastasis (P = 0.007) and combined systemic therapy (P = 0.036) were significantly associated with DCR, but not associated with PFS or OS. Conclusions: Some patients with advanced gastric cancer can benefit from apatinib. This study help us to identify patients who has potential benefit from apatinib.

Apatinib Plus Chemotherapy Shows Clinical Activity in Advanced NSCLC: A Retrospective Study.

Apatinib is an oral TKI with antiangiogenic properties, and it is currently approved for the treatment of advanced gastric cancer in China. This agent has also been tested in other human solid tumors, including non-small cell lung cancer (NSCLC). Since the combination of chemotherapy and an antiangiogenic agent has been shown to be a feasible strategy in NSCLC, it is conceivable that a similar approach combining apatinib with chemotherapy may yield clinical activity. With this in mind, we investigated the efficiency of apatinib in combination with pemetrexed or docetaxel in advanced NSCLC. We treated a total of 20 patients with metastatic NSCLC adenocarcinoma with apatinib in combination with either pemetrexed or docetaxel from January 2016 to March 2017. The performance status of these patients was 0 or 1. All of these patients had been previously treated with two or more lines of treatment and had experienced disease progression prior to study enrollment. The overall objective response rate (ORR) was 30%, with 6 patients who had partial response (PR), 10 patients who had stable disease (SD), and 4 patients who had progressive disease (PD). The main adverse events were skin rash, hypertension, palmar–plantar erythrodysesthesia syndrome, diarrhea, and fatigue. Nearly 30% of patients required interruption of treatment as a result of toxicity. Our study demonstrated that apatinib combined with systemic cytotoxic chemotherapy has clinical efficacy in patients with disease-refractory metastatic NSCLC and provides evidence for further studies investigating apatinib-based combination regimens.

The necessity of adjuvant radiotherapy for locally advanced gastric cancer in China.

Nearly 50% of the new gastric cancer cases and gastric cancer-related deaths worldwide occur in China. Although the Guidelines for the Diagnosis and Treatment of Gastric Cancer from the National Health Commission of the People’s Republic of China have explicitly emphasized the necessity of adjuvant chemoradiation for gastric cancer, few clinical institutions in China routinely administer postoperative adjuvant radiation therapy in patients with gastric cancer. At present, radical resection combined with postoperative chemotherapy alone is the most common treatment for locally advanced gastric cancer in China. However, several phase III prospective randomized controlled trials in Europe have shown that adjuvant chemotherapy alone after a radical resection does not improve the disease-free survival (DFS) or overall survival (OS) of patients with gastric cancer. As in Japan and South Korea, D2 radical resection is the recommended surgical approach for gastric cancer in China. However, several studies have shown that the rate of D2 resection in the treatment of gastric cancer patients in China is low. Nearly 50% of patients undergo a D0-1 radical resection, even at the leading gastric cancer centers in China. The results of the INT-0116 study in the US suggest that gastric cancer patients who undergo a D0-1 radical resection and have stage T3-4 or N+ disease should receive concurrent postoperative radiation therapy and chemotherapy. In conclusion, many patients with gastric cancer do not receive a standard D2 resection in China. As a result, it is important to consider postoperative adjuvant chemoradiation especially in those patients who undergo a D0-1 radical resection.

The necessity of adjuvant radiotherapy for locally advanced gastric cancer in China

Nearly 50% of the new gastric cancer cases and gastric cancer-related deaths worldwide occur in China. Although the Guidelines for the Diagnosis and Treatment of Gastric Cancer from the National Health Commission of the People’s Republic of China have explicitly emphasized the necessity of adjuvant chemoradiation for gastric cancer, few clinical institutions in China routinely administer postoperative adjuvant radiation therapy in patients with gastric cancer. At present, radical resection combined with postoperative chemotherapy alone is the most common treatment for locally advanced gastric cancer in China. However, several phase III prospective randomized controlled trials in Europe have shown that adjuvant chemotherapy alone after a radical resection does not improve the disease-free survival (DFS) or overall survival (OS) of patients with gastric cancer. As in Japan and South Korea, D2 radical resection is the recommended surgical approach for gastric cancer in China. However, several studies have shown that the rate of D2 resection in the treatment of gastric cancer patients in China is low. Nearly 50% of patients undergo a D0-1 radical resection, even at the leading gastric cancer centers in China. The results of the INT-0116 study in the US suggest that gastric cancer patients who undergo a D0-1 radical resection and have stage T3-4 or N+ disease should receive concurrent postoperative radiation therapy and chemotherapy. In conclusion, many patients with gastric cancer do not receive a standard D2 resection in China. As a result, it is important to consider postoperative adjuvant chemoradiation especially in those patients who undergo a D0-1 radical resection.

The combination of apatinib and S-1 for the treatment of advanced gastric cancer in China: A meta-analysis of randomized controlled trials.

Apatinib-targeted therapy is considered a promising treatment option for malignancies. This study systematically evaluated the efficacy and safety of the combination of apatinib and S-1 for the treatment of patients with advanced gastric cancer (GC). Clinical trials were searched from the PubMed, Cochrane Library, Embase, CNKI, and Wanfang databases. Outcome measures including therapeutic efficacy, quality of life (QoL), and adverse events were extracted and evaluated. Data from 8 trials including 393 patients with advanced GC were included. The results indicated that, compared with S-1 alone, the combination of apatinib with S-1 significantly improved patient partial response rate (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.21-3.02, P = .005), overall response rate (ORR, OR = 2.40, 95% CI = 1.51-3.82, P = .0002), and disease control rate (DCR, OR = 2.78, 95% CI = 1.51-5.10, P = .0010), whereas the rates of complete response (CR, OR = 2.38, 95% CI = 0.93-6.12, P = .07) and stable disease (SD, OR = 0.99, 95% CI = 0.64-1.54, P = .97) and QoL (OR = 1.22, 95% CI = 0.51-2.92, P = .66) did not differ significantly. Moreover, the group receiving the combined therapy had higher rates of hand-foot syndrome (OR = 2.23, 95% CI = 1.19-4.17, P = .01), hypertension (OR = 8.85, 95% CI = 4.07-19.26, P < .00001), albuminuria (OR = 11.25, 95% CI = 3.32-38.06, P = .0001), and hemoglobin reduction (OR = 3.19, 95% CI = 1.32-7.67, P = .010), whereas analysis of other adverse events did not show significant differences (P > .05). The combination of apatinib and S-1 is more effective for GC treatment than S-1 alone. However, this combined treatment could lead to increased hand-foot syndrome, hypertension, albuminuria, and hemoglobin reduction. Therefore, the benefits and risks should be considered before treatment.

Therapeutic arrangement and strategies in perioperative treatment of locally advanced gastric cancer from the view of whole-process management

The incidence of gastric cancer is high in China. Most patients are advanced incurable and by surgery at diagnosis. At present, the treatment of advanced gastric cancer in China has been mainly based on multidisciplinary treatment including surgery, chemotherapy, radiotherapy, molecular targeted therapy, as well as immunotherapy. In the pursuit of the ultimate goal of prolonging survival, from the perspective of management throughout the patient journey, we should further optimize and arrange the strategies, methods, techniques and timing in perioperative treatment. There are still many unsolved problems to promote gastric cancer surgery from simple technical resection to biological resection. Treatment procedure based on evidence-based medicine and efficacy evaluation criteria may result in correct decision. In addition molecular markers based on gene sequencing may help select oppropriate agents and predict efficacy and prognosis. In clinical practice, how to achieve individualized treatment based on precise staging and goal orientation is the aim of continuous efforts to prolong the survival of advanced gastric cancer patients.

Effect of ECOG PS on outcome of advanced or metastatic gastric patients treated with apatinib: Analysis from a post-marketing phase IV study.

e16026Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. The real benefits of apatinib for different patients (pts) with ECOG ...

Effects of apatinib dose interruptions on safety and efficacy in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting.

142 Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. Due to toxicity, many pts underwent temporary interruptions during treatment. We analyzed the data from a phase IV clinical trial of Ahead-G201 to evaluate the relationship between dose interruption, drug safety and efficacy. Methods: At the cutoff date of Jul 10, 2017, Ahead-G201 study enrolled 1037 pts. The adverse events (AEs) and clinical efficacy were evaluated for pts with no, 1, 2 and ≥3 dose interruptions. Results: 336 of 1037 pts underwent dose interruptions during apatinib treatment: 1 interruption in 183 pts; 2 interruptions in 67 pts; and ≥3 interruptions in 86 pts. The toxicity and efficacy for them were listed in Table. For safety, pts with no interruption had the lowest incidence of all AEs (59.3%) and grade 3-4 AEs (30.0%). Pts with ≥3 interruptions had the highest objective response rate (ORR, 20.3%) and disease control rate (DCR, 82.6%). Moreover, these pts got median progression-free survival (mPFS) of 6.6 mos and median overall survival (mOS) of 9.4 mos, which were the longest among 4 groups. Furthermore, multivariate analysis revealed that ≥3 interruptions of apatinib bring much more efficacy benefit both in mPFS (6.6 vs 3.8 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.7) and mOS (9.4 vs 6.6 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.8) for pts, than those with no interruption. Conclusions: Current results indicated that dose interruptions are required to manage toxicity and it is necessary to explore an optimal dosing pattern of apatinib in advanced gastric cancer. Clinical trial information: NCT02426034. [Table: see text]

S-1 combined with cisplatin versus cisplatin alone for the treatment of advanced gastric cancer

We aimed to assess the efficacy and safety of S-1 combined with cisplatin (SC) over cisplatin alone (C) for the treatment of advanced gastric cancer in China. Between July 2009 and June 2011, 72 eligible patients with advanced gastric cancer were selected and divided randomly into two groups. Thirty-six patients received SC, with S-1 on days 1 through 14 of a 21-day cycle and cisplatin (60 mg/m on day 1) every 4 weeks for two cycles. The other 36 patients were administered only cisplatin (in the same manner as SC). The primary outcome was overall survival. The secondary outcomes were progression-free survival and adverse events. The 2-year overall response rate was 51.5 and 42.3% for the SC and C groups, respectively, and the difference was statistically significant, whereas the median overall survival was 9.4 months (range, 1.9-24.4 months) and 7.6 months (range, 1.7-21.4 months), respectively (P=0.039). The median progression-free survival was 7.7 months for SC (range, 1.8-19.4 months), whereas it was 6.5 months (range, 1.5-16.4 months) for C (P=0.047). The toxicity profile was similar in both groups. In summary, we have shown that S-1 combined with cisplatin is more effective, with acceptable toxicity in comparison with cisplatin alone in Chinese patients with advanced gastric cancer. Chinese Clinical Trials Register: ChiCTR-TRC-13003993.

Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): Chinese subgroup analysis

To evaluate the efficacy and safety profile of XELOX (capecitabine/oxaliplatin) in patients with locally advanced gastric cancer who underwent curative D2 resection in China. This is a subgroup analysis of Chinese patients in the capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC study), which was a randomised, open-label, multicentre, parallel-group, phase III( study in the Asia-Pacific region. A total of 100 gastric cancer patients who received curative D2 gastrectomy were enrolled in this study and were randomly assigned to either XELOX group (oral capecitabine combined with intravenous oxaliplatin chemotherapy) or the control group (surgery alone). This study aims to compare the 3-year disease-free between the two groups. Subgroup analysis showed that 3-year DFS rate were 78% and 56% in XELOX and control group, respectively. The risk of relapse in XELOX group was reduced by 59% (HR=0.41, 95%CI:0.20-0.85, P=0.013), compared with the control group. The 3-year overall survival rate were 78% and 66% in XELOX and control group, with no statistically significant difference (HR=0.55, 95%CI:0.26-1.16, P=0.110). Adjuvant XELOX chemotherapy following D2 gastrectomy may improve the survival in patients with advanced gastric cancer in China.

Risk factors for No. 12p and No. 12b lymph node metastases in advanced gastric cancer in China

Background. The risk factors for No. 12p and No. 12b lymph node (LN) metastases in advanced gastric cancer (GC) remain controversial. The aim of this study was to investigate the risk factors for No. 12p and No. 12b LN metastases in advanced GC.Methods. From January 1999 to December 2005, a retrospective analysis of 163 patients with advanced GC who underwent D2 lymphadenectomy in addition to No. 12p and No. 12b LN dissections was conducted. Potential clinicopathological factors that could influence No. 12p and No. 12b LN metastases were statistically analyzed.Results. There were 15 cases (9.2%) with No. 12p LN metastases and 5 cases (3.1%) with synchronous No. 12b LN metastases. A logistic regression analysis revealed that the Borrmann type (III/IV versus I/II, P = 0.029), localization (lesser/circular versus greater, P = 0.025), and depth of invasion (pT4 versus pT2/pT3, P = 0.009) were associated with 11.1-, 3.8-, and 5.6-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. A logistic regression analysis also showed that No. 5 (P = 0.006) and No. 12a (P = 0.004) LN metastases were associated with 6.9- and 11.3-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. In addition, significant differences in 5-year survival of patients with and without No. 12p and No. 12b LN metastases were observed (13.3% versus 35.1%, P = 0.022).Conclusion. We conclude that Borrmann type, localization, and depth of invasion are significant variables for identifying patients with No. 12p and No. 12b LN metastases. Individuals with No. 5 or No. 12a LN metastases should be on high alert for the possibility of additional metastases to the No. 12p and No. 12b LNs.

Cost-effectiveness analysis of chemotherapy for advanced gastric cancer in China

To assess the economics of various chemotherapeutic regimens for advanced gastric cancer (AGC), and to select the best cost-effective regimen for the common Chinese patients. Data source used in this study was the Chinese Biomedical Disk Database. Patients were diagnosed as AGC and any regimen was eligible. Outcome measures included median survival time (MST) and percentage of complete and partial response (CR+PR). Economic statistics was per capita direct medical cost (DMC) of a single cycle. TreeAge Pro Healthcare 2007 software was used to carry out cost-effectiveness and incremental cost-effectiveness analysis. Sensitivity analyses were applied by altering willingness-to-pay and annual discount rate, and also re-analyzed by excluding the studies with apparent heterogeneity. Seven retrospective economics studies on 760 patients were included. 5-fluorouracil-based regimens were universal, and also some new agents were involved, such as docetaxel, paclitaxel, and oxaliplatin. By processing analysis, we could recommend etoposide, leucovorin and 5-fluorouracil (ELF) regimen as preference, with a DMC/MST ratio of 2543 RBM/11.7 mo and a DMC/CR+PR ratio of 2543 RMB/53.3%. Uracil-tegafur, etoposide and cisplatin (FEP) or 5-fluorouracil, adrimycin/epirubin and mitomycin (FAM) regimens could be regarded as optional first-line chemotherapy for AGC in common Chinese patients. With no regard for willingness-to-pay, the docetaxel, cisplatin and 5-fluorouracil (DCF) regimen could be chosen as either a first- or a second-line chemotherapy, with a DMC/CR+PR ratio of 9979 RMB/56.3%. 5-fluorouracial regimens are still considered the mainstream for AGC, while new agents such as taxanes are optional. More randomized clinical trials are required before any mandatory recommendation of certain regimens for patients with AGC in China is made.