Metastatic Advanced Gastric Cancer Research Articles

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06)

BackgroundImmune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC.MethodsWe retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan).ResultsA total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy.ConclusionsNo significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.Trial registrationThis study was registered in the Clinical Trial Registry of Korea (https://cris.nih.go.kr: KCT 0007732).

Efficacy of bevacizumab combined with apatinib in the treatment of advanced metastatic gastric cancer.

To evaluate the clinical efficacy and safety of bevacizumab combined with apatinib in the treatment of advanced metastatic gastric cancer, providing insights for treatment decisions. We conducted a single-center retrospective study involving patients with metastatic gastric cancer treated with apatinib, with or without bevacizumab, between August 2018 and April 2021 at Nanchang Medical College. Data on efficacy, adverse events, response rates, and quality of life were collected and compared. No significant differences were observed in complete remission, partial response, stable disease, disease progression, objective response rate, or disease control rate between the groups (all P>0.05). The median progression-free survival was 9.23 months in the control group and 9.94 months in the observation group (P=0.587). Median overall survival (OS) was 19.64 months in the control group and 26.44 months in the observation group (P=0.187). Univariate and multivariate analyses identified combination therapy with apatinib and bevacizumab, primary lesion resection, and number of metastatic organs as independent prognostic factors for OS. Scores for role, emotional, somatic, cognitive, and social functions were significantly higher in the observation group post-intervention (all P<0.05). In patients with advanced metastatic gastric cancer, combined therapy with bevacizumab and apatinib significantly improved OS, enhanced response rates, and increased rates of early and maximal tumor shrinkage.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

The Role of Angiogenesis Targeted Therapies in Metastatic Advanced Gastric Cancer: A Narrative Review.

Since bevacizumab was first approved by the U.S. Food and Drug Administration as an anti-angiogenic therapy in 2004, angiogenesis-targeted therapy has been developed for various types of solid tumors. To date, ramucirumab and apatinib are clinically available as treatments for metastatic advanced gastric cancer (AGC). Ramucirumab demonstrated prolonged survival as second-line therapy of metastatic AGC in the RAINBOW and REGARD trials. However, neither ramucirumab extended survival in treatment-naïve patients with AGC in the RAINFALL or RAINSTORM trials nor bevacizumab in the AVAGAST and AVATAR trials. Apatinib demonstrated superior efficacy over the best supportive care in a Chinese phase III trial but not in an international phase III (ANGEL) trial. Currently, combination therapy of ramucirumab with irinotecan or FTD/TPI is being evaluated in the third-line setting, assessing the efficacy of continuous angiogenesis inhibition from second- to third-line therapy. Recently, the role of angiogenesis inhibition via immunomodulators is attractive to clinicians. Emerging results of several early-phase clinical trials indicated the promising antitumor activity of angiogenesis inhibition in combination with immune therapy. This review offers an overview of the history of clinical trials focused on anti-angiogenic for patients with AGC and presents future perspectives in this area.

Oncoguía de cáncer gástrico 2023

Gastric cancer ranks fifth in incidence worldwide, and Mexico is the sixth most frequent malignant neoplasm. Risk factors associated with gastric cancer are age (&gt; 65 years), being male, a diet high in salt and nitrates, smoked and processed meats, vitamin C deficiency, smoking, heavy alcohol consumption, and infection by H. pylori and Bar Epstein virus. In Western countries, gastric cancer is associated with obesity and gastroesophageal reflux disease, predominantly proximal or in the cardia. The clinical picture is nonspecific in the early stages. Endoscopy allows biopsy for histopathological confirmation. Endoscopic treatment is the best option in tumors confined to the mucosa due to the high resectability rate, the organ´s appearance, and low recurrence. Surgical treatment is the best alternative for locoregional oncological control in the locally advanced stage. Likewise, the benefit of perioperative chemotherapy has been demonstrated. Adjuvant chemotherapy is recommended for patients without previous treatment and who initially underwent a total gastrectomy. Unresectable or metastatic advanced gastric cancer has a poor prognosis, although it has recently improved. This oncoguía included recommendations for diagnosis, staging, and treatment based on our Instituto Nacional de Cancerología´s experience and the most recently published evidence.

Effect of Severe Renal Dysfunction on the Plasma Levels of DNA-Reactive Platinum after Oxaliplatin Administration.

Higher amounts of circulating ultrafilterable platinum (fPt) are found in patients with renal dysfunction receiving a constant dose of oxaliplatin. However, the increased systemic fPt levels do not increase oxaliplatin-induced toxicities. We hypothesized that renal dysfunction has minimal effect on the elimination rate of reactive fPt, and that the DNA-binding capacity is one of the properties of reactive Pt species. This study aimed to quantify DNA-reactive fPt in plasma and to evaluate the impact of severe renal dysfunction on its pharmacokinetics. The pharmacokinetics of oxaliplatin was assessed in rats with bilateral nephrectomy (BNx) and in a hemodialysis patient who received mFOLFOX7 therapy for advanced metastatic gastric cancer. The platinum concentrations were determined using inductively coupled plasma-mass spectrometry. The amount of DNA-reactive fPt in the plasma was evaluated by the reaction between plasma and calf thymus DNA. Compared to the sham group in rats, the BNx group had significantly higher plasma total fPt concentrations at 24 h after drug administration. However, there was no significant difference in the plasma levels of DNA-reactive fPt between the two groups. In a hemodialysis patient, the plasma levels of total fPt decreased to 35.9 and 7.3% at 2 and 14 d after treatment, respectively. The plasma level of DNA-reactive fPt also decreased to 1.9 and 0.6%, respectively, on these days. This study showed that severe renal dysfunction has a limited effect on the plasma levels of DNA-reactive fPt after oxaliplatin administration.

P73-4 Experience with nivolumab in advanced metastatic gastric cancer

Nivolumab has been shown to be effective and safe for advanced metastatic gastric cancer (mGC). It is recommended as an option after the second-line treatment for advanced mGC in Japan. The present study has investigated the effectiveness and safety of nivolumab in our facility with advanced mGC.

Frequency and prognostic impact of cachexia during drug treatment for unresectable advanced gastric cancer patients.

Patients with unresectable advanced metastatic gastric cancer have a poor prognosis. This study examined the incidence and prognostic impact of cachexia during systemic drug treatment in such patients. We enrolled patients with unresectable advanced gastric cancer who were treated with chemotherapy at Kochi Medical School from 2007 to 2020. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20kg/m2 within the past 6months. Associations between clinicopathological parameters, cancer cachexia, and the overall survival were analyzed. Cancer cachexia occurred in 55.2% of 134 enrolled patients 6months after chemotherapy. The incidence of cancer cachexia in initial unresectable gastric cancer was significantly higher than that in patients with recurrent cancer after curative resection. The median overall survival was significantly lower in the patients with cancer cachexia than in those without cancer cachexia at 6months after starting systemic chemotherapy (13.7months vs. 21.6months, P = 0.032). Cancer cachexia at 6months of starting treatment and CRP > 0.14 were identified as significantly associated with poor outcomes in a multivariate analysis (hazard ratio [HR] 1.339, 95% confidence interval [CI] 1.160-2.085, P = 0.019; HR 1.885, 95% CI 1.124-3.161, P = 0.016); respectively). Cancer cachexia was frequently observed in unresectable advanced gastric cancer patients who received chemotherapy and was useful as a prognostic factor for the overall survival.

Elemene-containing hyperthermic intraperitoneal chemotherapy combined with chemotherapy for elderly patients with peritoneal metastatic advanced gastric cancer.

BACKGROUNDAlmost all elderly patients with peritoneal metastatic gastric cancer (PGC) are unlikely to tolerate cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and adjuvant chemotherapy. However, determining how to optimize the treatment strategy for such patients has always been a clinical problem. Both HIPEC and palliative adjuvant chemotherapy can benefit patients with PGC. Therefore, optimizing HIPEC and chemotherapy regimens has potential clinical value in reducing side effects, and improving treatment tolerance and clinical effectiveness.AIMTo explore the effect of HIPEC containing elemene, which is an anti-cancer component extracted in traditional Chinese herbal medicine, combined with reduced capecitabine and oxaliplatin (CapeOx) chemotherapy regimens, in elderly patients with PGC.METHODSIn the present study, 39 of 52 elderly PGC patients were included and assigned to different HIPEC treatment groups [lobaplatin group (group L) and mixed group (group M)] for analysis. Lobaplatin was used for all three HIPECs in group L. In group M, lobaplatin was used in the middle of the three HIPECs, and elemene was used for the first and third HIPEC. After HIPEC, patients received CapeOx chemotherapy. The incidence of complications (abdominal infection, lung infection, and urinary tract infection), myelosuppression, immune function (CD4/CD8 ratio), average length of hospital stay, and prognosis were compared between these two groups.RESULTSThere was no significant difference in the incidence of complications between the two groups during hospitalization (P > 0.05). Compared to patients in group M, patients in group L exhibited severe myelosuppression (P = 0.027) and increased length of hospital stay (P = 0.045). However, no overall survival benefit was observed in group M. Furthermore, the immune function of patients in group M was less affected (P < 0.001), when compared to that of patients in group L. The multivariate analysis suggested that the cycles of chemotherapy after perfusion significantly affected the prognosis of patients in both groups.CONCLUSIONCompared to the lobaplatin-based HIPEC regimen, the administration of elemene reduced the myelosuppression incidence in elderly PGC patients. The present study sheds light on the implementation of this therapeutic strategy for this set of patients.

The prognostic value of baseline hematological parameters of peripheral blood in metastatic gastric cancer treated with apatinib.

Background: There is strong evidence that apatinib is effective in the treatment of third- or later-line advanced metastatic gastric cancer (mGC). Hematology prediction index is a convenient and cheap method to predict the prognosis of disease. However, the prognosis of baseline hematological parameters of peripheral blood, such as neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen 125 (CA125) and albumin (ALB) on mGC treated with apatinib have not been identified.Methods: We retrospectively analyzed mGC received apatinib between 1 January 2014 and 30 June 2021. Survival analyses were performed using the Kaplan-Meier method and Cox-proportional hazards model.Results: A total of 117 patients were included in this study. The cutoff value of NLR, CA125 and ALB was 2.25, 19.24 U/ml and 37.60 g/L, respectively. The disease control rates (DCR) in the high and low NLR groups were 52.94% and 73.47% (P=0.024); 48.28% and 74.58% (P=0.003) in high and low CA125 groups; 72.97% and 41.86% (P=0.001) in high and low ALB groups. By survival analysis, increasing NLR (P=0.003), CA125 (P<0.001) and decreasing ALB (P<0.001) predicted a shorter PFS after apatinib. NLR (P=0.015), CA125 (P=0.004) and ALB (P=0.005) were significantly predictors for PFS in mGC treated with aptinib.Conclusion: Increasing NLR, CA125 and decreasing ALB were associated with poorer clinical efficiency and prognosis after apatinib treatment.

In vitro and in vivo Evaluation of a Novel Estrogen-Targeted PEGylated Oxaliplatin Liposome for Gastric Cancer.

BackgroundChemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin.MethodsFour kinds of oxaliplatin (OXA) liposomes were prepared by film hydration method. The obtained formulations were characterized in terms of entrapment efficiency (EE), particle size, and so on by HPLC and DLS (dynamic light scanning). The morphology of ES-SSL-OXA was detected by transmission electron microscope (TEM). The in vitro and in vivo targeting effect of ES-SSL-OXA was verified by fluorescence microscopy and in vivo imaging system in gastric cancer cells (SGC-7901) and tumor-bearing athymic mice. The in vitro and in vivo antitumor efficacies of ES-SSL-OXA were investigated on SGC-7901 cells and athymic tumor-bearing mice. Pharmacokinetic, biodistribution, and acute toxicity tests of ES-SSL-OXA were performed on ICR mice.ResultsThe ES-SSL-OXA exhibited an average particle size of about 153.37 nm with an encapsulation efficiency of 46.20% and low leakage rates at 4°C and 25°C. In vivo and in vitro targeting study confirmed that ES-SSL-OXA could effectively target the tumor site. The antitumor activity demonstrated the strongest inhibition in tumor growth of ES-SSL-OXA. Pharmacokinetics and acute toxicity study showed that ES-SSL-OXA could significantly improve the metabolic behavior and toxicity profile of oxaliplatin.ConclusionIn this study, a novel estrogen-targeted long-acting liposomal formulation of OXA was successfully prepared. ES fragment effectively targeted the delivery system to tumor tissues which highly express estrogen receptor, providing a promising therapeutic method for gastric cancer in clinic.

P44-6 Twelve cases with metastatic gastric cancer were treated with chemo-immunotherapy

Metastatic gastric cancer has a poor prognosis, despite the development of chemotherapeutic and biological agents. The recent SOLAR study demonstrated better efficacy of S-1, oxaliplatin, plus leucovorin (SOL), compared to S-1 plus cisplatin, in advanced gastric cancer. We have conducted a preliminary study of SOL in combination with lentinan, purified β-glucan from Shiitake mushroom, during these 4 years. The clinical study was approved by ethics committee of Nagoya Memorial Hospital in 2016. After explaining the protocol of this study, patients with recurrent or unresectable gastric cancer were enrolled, if they have intention to participate. Medical records were retrospectively reviewed to determine the objective response rate (ORR), disease control rate, overall survival (OS), and adverse effects. Twelve patients with metastatic gastric cancer (liver 3, lung 2, peritoneal 11, ascites 9) (age; 59-81) (gender; male 9, female 3) were treated with SOL in combination with lentinan at a first-line regimen. The cycles ranged from 4 to 14. ORR and disease control rate were 50% (CR 1, PR 5) and 92%, respectively. One CR case survives for more than 18 months without any recurrence, who is maintained by S-1 plus leucovorin combined with lentinan. As for the adverse events, peripheral neuropathy was the most common, which was observed in all patients. However, there were no severe degree of side effects such as febrile neutropenia and diarrhea. SOL in combination with lentinan can be a promising option for the treatment of far advanced metastatic gastric cancer, due mainly to its safety.

Clinical effectiveness of apatinib at different doses in patients with advanced gastric cancer as the third-line or further treatment: Results from a post-marketing phase IV study.

e16037 Background: Apatinib, a highly selective VEGFR2 inhibitor, has shown a clinical benefit as third-line or further-line treatment in patients with gastric cancer in a randomized phase III study with the initial dose of 850mg. However, the study was conducted in a small scale (n = 267) under standardized conditions. Here, we assessed exposure and effectiveness of apatinib at different doses using data collected from a post-marketing phase IV study that included a broader patient population with a larger sample size. Methods: Patients with advanced or metastatic advanced gastric cancer or gastroesophageal junction adenocarcinoma who were aged 18-75 with ECOG performance status of 0-2 and failed at least two lines of chemotherapy were enrolled. Apatinib was recommended with an initial dose of 850 mg q.d orally, while the initial dose was determined at the discretion of the investigators. Administration of apatinib regarding the initial dose, duration of treatment, dose modification, average daily exposure dose (ADED) and its effect on progression-free survival (PFS) and overall survival (OS) were analyzed. Results: A total of 2004 patients were included in the intention-to-treat population. The median age was 59 (range, 19-85) years, 71.8% of patients were male, 84.2% had ECOG performance status of 0-1; 96.4% had stage IV disease, and 98.8% had metastases, among which 34.2% with more than 2 metastases. Five patients did not receive therapy. Compared to 5.5% of patients with the initial dose &gt; 500mg, 94.1% was given at the initial dose≤500mg; 8.6% had ADED &gt; 500mg and 91.1% had ADED ≤500mg. The median duration of treatment was 56 days. Treatment interruption and discontinuation, and dose reduction occurred in 34.4%, 24.5%, and 13.7% of patients due to adverse events, respectively. Survival analyses in the initial dose ≤500mg/ &gt; 500mg subgroups showed median PFS of 2.6 months (95%CI 2.20-2.79) vs 2.7 months (95% CI 1.91-3.32), median OS of 5.6 months (95% CI 5.26-5.95) vs 5.9 months (95% CI 4.40-6.87). In the ADED ≤500mg/ &gt; 500mg subgroups, the median PFS was 2.6 months (95% CI 2.14-2.76) vs 3.0 months (95% CI 2.27-3.61), and median OS was 5.7 months (95% CI 5.32-6.08) vs 6.1 months (95% CI 5.36-7.72). Conclusions: In conclusion, more than 90% of the patients received a lower dose regimen, which indicate dosage of 500mg or lower is a tolerated exposure. Furthermore, dose at 500mg or lower produced similar efficacy to that more than 500mg. Clinical trial information: NCT02426034.

Impact of follow-up on generalized pairwise comparisons for estimating the irinotecan benefit in advanced/metastatic gastric cancer

Background and objectivesThe net treatment effect (∆) is a new method to assess the treatment benefit that combines multiple time-to-event, binary and continuous endpoints according to a pre-specified sequence. It represents the net probability for a random patient treated in the experimental arm to have a better overall outcome than a random patient from the control arm does. We aimed at characterizing the impact of follow-up on ∆ estimated from both time-to-event and binary toxicity endpoints, in randomized controlled trials (RCTs) of irinotecan-based regimen in advanced/metastatic gastric cancer (AGC). Study designThree RCTs are reanalysed. The net treatment effect using from one to three outcomes (i.e. overall survival, time to progression and toxicity in this order) and the hazard ratio (HR) were estimated after various cut-off dates and compared to the values obtained after complete follow-up were reported. ResultsIn all three RCTs (897 patients), the irinotecan-based regimen was superior to the non-irinotecan containing regimen in terms of HR and ∆. This superiority was lower when the net treatment effect also accounted for toxicity. The HR was slightly less influenced by an incomplete follow-up than ∆ was, but correction proposed by Péron to account for censored observations showed quite robust results. ConclusionsThe net treatment effect using Péron's correction can be used in case of interim analyses or high censoring rates. In addition to relative measures such as the hazard ratio, it provides a simple mean to evaluate the net treatment effect with and without toxicity outcomes.

Treatment options for oligometastatic gastric cancer

HintergrundZum Zeitpunkt der Diagnosestellung des Magenkarzinoms haben ca. zwei Drittel der Patienten bereits Metastasen. Wichtig ist es, die Oligometastasierung von der diffus metastasierten Situation abzugrenzen. Die S3-Leitlinie hat die Definition der Oligometastasierung erstmals in die Leitlinie aufgenommen.FragestellungKann das Überleben von Patienten mit Oligometastasierung mittels Resektion des Tumors und der Metastase kombiniert mit perioperativer Chemotherapie verbessert werden?Material und MethodenIn dieser Übersichtsarbeit wird die Datenlage der aktuellen Literatur dargestellt.ErgebnisseDie holländische Magenkarzinomstudie stellte ein verbessertes medianes Überleben für Patienten mit singulären Metastasen fest, wenn diese reseziert wurden. Aufgrund der Resultate der deutschen AIO-FLOT3-Studie, in der sich das mediane Überleben von Patienten mit Oligometastasen mit multimodaler Therapie verdoppelte, wurde die AIO-FLOT5(RENAISSANCE)-Studie initiiert. Diese randomisiert limitiert metastatische Patienten nach neoadjuvanter Chemotherapie entweder zu Resektion gefolgt von Chemotherapie oder zu definitiver Chemotherapie. Weitere randomisierende Studien untersuchen den Nutzen von Antikörpern und Immun-Checkpoint-Inhibitoren beim lokoregionalen und metastasierten Magenkarzinom mit vielversprechenden Resultaten.DiskussionDie Resultate der aktuellen Studien werden zeigen, ob Patienten mit Oligometastasierung von einer multimodalen Therapie mit Resektion profitieren. Die eindeutige Definition der Oligometastasierung, eine Beurteilung des Ansprechens nach neoadjuvanter Chemotherapie und eine realistische Einschätzung der R0-Resektion werden bei der entsprechenden Patientenselektion hilfreich sein.

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting. MethodsFrom September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR). ResultsTwenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34–4.66]. The median OS was 4.5 months (95%CI: 3.49–5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P = 0.030) and PFS (P = 0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%). ConclusionApatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer. Trial registrationAHEAD-G202 (NCT02668380).

Healthcare Utilization and Total Costs of Care Among Patients with Advanced Metastatic Gastric and Esophageal Cancer

Aim: Study first-line (1L) treatment patterns and economic outcomes among patients with advanced metastatic gastric cancer (GC) and esophageal cancer (EC). Materials & methods: Newly diagnosed patients with systemic GC and EC treatments were identified between 1January 2011 and 31 July2017; costs were presented as per patient per month (PPPM) basis. Results: Study included 392 GC and 436 EC patients. Most frequently used 1L regimens were: 5-fluorouracil (5-FU)+oxaliplatin (22.5%) and epirubicin + cisplatin + 5-FU (ECF)/ECF modifications (21.9%) in patients with GC; and carboplatin+paclitaxel (29.6%) and 5-FU+oxaliplatin (11.5%) in EC patients. Mean all-cause costs were US$16,242 PPPM for GC, and $18,384 PPPM for EC during 1L treatment. Conclusion: GC and EC were resourceintensive and costly. High costs and short treatment durations underscored a gap in care in 1L treatment.

S-1 Plus Leucovorin and Oxaliplatin in Combination with Lentinan as First-line Therapy in Patients with Metastatic Gastric Cancer

Background: Metastatic gastric cancer has a poor prognosis, despite recent therapeutic improvements. The phase 3 SOLAR study confirmed better efficacy of S-1, oxaliplatin, and leucovorin (SOL) than S-1 plus cisplatin in advanced gastric cancer. Lentinan, (1, 3)-glucan purified from Shiitake mushrooms, has been reported to improve the overall survival of cancer patients receiving chemotherapy. We conducted a preliminary study of SOL combined with lentinan during these 4 years. Methods: The clinical study was approved by the ethics committee of Nagoya Memorial Hospital in 2016. After explaining the protocol of this study, patients with recurrent or unresectable gastric cancer were enrolled, if they had the intention to participate. Medical records were retrospectively reviewed to determine the objective response rate (ORR), disease control rate, overall survival, and adverse effects. Results: Twelve patients (age: 59-81 years; sex: 9 men, 3 women) with metastatic gastric cancer (liver: 3, lung: 2, peritoneal: 12, ascites: 9) were treated with SOL in combination with lentinan as the first-line regimen. The cycles ranged from 4 to 15. The ORR and disease control rates were 58.3% (complete response [CR], 1; partial response, 6) and 91.7%, respectively. One patient with CR survived for &gt; 23 months after the initiation of chemotherapy. Concerning adverse events, peripheral neuropathy was the most common event observed in all patients. However, there were no severe side effects, such as febrile neutropenia and diarrhea. Conclusions: SOL combined with lentinan can be a promising option for the treatment of far advanced metastatic gastric cancer.

803P - Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to systematically evaluate the efficacy and safety of apatinib targeted therapy in advanced AFPGC and investigate the predictive factors of apatinib treatment. MethodsThree hundred thirty-seven patients were enrolled in the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer. Among them, we recruited all the patients identified with AFPGC for this study. The clinical features, efficacy, adverse events, and survival were assessed. ResultsWe enrolled 21 patients with AFPGC into this study. The objective response rate (ORR) of apatinib in patients with AFPGC was 10%, whereas the disease control rate (DCR) was 70%. The median progression-free survival (PFS) was 3.5 months [95%confidence interval (CI): 2.34-4.66]. The median overall survival (OS) was 4.5 months (95%CI: 3.49-5.51). The common grade adverse events (AEs) were hypertension (33.3%), fatigue (23.8%), and myelosuppression (19.0%). The most common grade 3 to 4 AEs were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%). Carcinoembryonic antigen (CEA) elevation was considered to be a potential independent predictive factor (P=0.030). ConclusionsApatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC. Clinical trial identificationAHEAD-G202 (NCT02668380). Editorial acknowledgementElsevier Language Editing Services. Legal entity responsible for the studyThe author. FundingJiangsu HengRui Medcine Co., Ltd.; 2016 PUMCH Science Fund for Junior Faculty (Pumch-2016-1.13); Chinese Anti-cancer Association (CORP-143-09). DisclosureThe author has declared no conflicts of interest.

Nab-paclitaxel plus ramucirumab combination therapy as second-line with advanced gastric cancer:Retrospective study

Abstract Background Metastatic advanced gastric cancer(AGC) is predominantly a disease in JAPAN. A Phase II trial show the efficacy and safety of nab-paclitaxel plus ramucirumab combination therapy for previously treated advanced gastric cancer but the benefits of second-line chemotherapy in real world including elderly patients remain uncertain. Methods We retrospectively examined pts with AGC who were treated in Saga-university hospital. The key inclusion criteria were ECOG PS 0-2 and refractory/intolerant to first line treatments. The objective was the efficacy of Ramucirumab plus nab-Paclitaxel as second-line therapy in real-world patients with AGC. Results A total of 14 patients underwent second-line chemotherapy for gastric cancer between 2017 and 2018 at our hospital. We evaluated the outcome in terms of median progressive free survival (PFS) and overall survival (OS) respectively. The ORR assessed was 40.0% and the DCR was 100%. The median PFS was 7.6 months (95% CI 2.1-17.5). The median OS was not reached at the data cutoff. The main treatment-related over grade 2 adverse events were decreased neutrophil count (60%),hypertension (26%) and proteinuria (0%). Conclusions Nab-paclitaxel plus ramucirumab combination therapy shows similar treatment results to the Phase II study and toxicities were safety manageable. This treatment regimen could be a useful second line treatment option for patients with previously treated AGC.