The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer

Abstract Omentectomy is conducted for advanced gastric cancer (AGC) patients as radical surgery without an adequate discussion of the effect. This study was conducted to reveal the impact of omentum-preserving gastrectomy on postoperative outcomes. AGC patients with cT3 and 4 disease who underwent total or distal gastrectomy with R0 resection were identified retrospectively. They were divided into the omentum-preserved group (OPG) and the omentum-resected group (ORG) and matched with propensity score matching with multiple imputation for missing values. Three-year overall survival (OS) and 3-year relapse-free survival (RFS) were compared, and the first recurrence site and complications were analysed. The numbers of eligible patients were 94 in the OPG and 144 in the ORG, and after matching, the number was 73 in each group. No significant difference was found in the 3-year OS rate (OPG: 78.9 vs. ORG: 78.9, P = 0.54) or the 3-year RFS rate (OPG: 77.8 vs. ORG: 68.2, P = 0.24). The proportions of peritoneal carcinomatosis and peritoneal dissemination as the first recurrence site and the rate and severity of complications were similar in the two groups. Omentectomy is not required for radical gastrectomy for AGC.

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The Chinese subgroup from a randomized phase III study of lapatinib in combination with weekly paclitaxel versus weekly paclitaxel alone as second-line treatment of HER2-amplified advanced gastric cancer (AGC) in Asian countries.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4109 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4109-4109 ◽

Cited By ~ 1

Author(s):

Guo-ping Sun ◽

Yan Sun ◽

Rui-hua Xu ◽

Jian-Ming Xu ◽

Jin Li ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Regional Differences ◽

Mainland China ◽

Progression Free Survival ◽

Phase Iii ◽

Weekly Paclitaxel ◽

Phase Iii Study ◽

The Impact ◽

Chinese Subjects

4109 Background: TyTAN is a randomized phase III study to evaluate lapatinib (L) plus paclitaxel (P) in pretreated HER2 amplified (HER2+) advanced gastric cancer (AGC). The disease characteristics and GC treatment pattern differed in Japan and in China, so a subgroup analysis was done for subjects recruited in mainland China. Methods: AGC subjects with prior 5-FU and/or cisplatin and HER2 amplification by fluorescence in situ hybridization (FISH) in tumor tissue were randomized 1:1 to L (1500mg QD) and P (80mg/m2, Day 1, 8, 15 q4w) or P alone (80mg/m2, Day 1, 8, 15 q4w). 1st endpoint was overall survival (OS). 2nd endpoints included progression free survival (PFS), overall response rate (ORR) and safety. A total of 95 subjects recruited from mainland China. Results: TyTAN was not significant in OS (HR0.84), but 2 months OS improvement was observed in L+P arm. The results from Chinese subgroup are shown in the Table. The most common adverse events in Chinese subjects were similar as in whole population (neutropenia, diarrhea, rash, leukopenia, anemia, fatigue). Compare to the overall results, less Chinese subjects reported nausea and vomiting. Conclusions: This analysis showed that there were clear regional differences as observed between subjects in China and Japan. The addition of L to P was associated with a clinically meaningful benefit in subjects recruited from mainland China. These data warrants further prospective evaluations on the impact of regional differences in the outcome of HER+ GC in East Asian patients. Clinical trial information: NCT00486954. [Table: see text]

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The impact of the preoperative hand grip strength on the long-term outcomes after gastrectomy for advanced gastric cancer

Surgery Today ◽

10.1007/s00595-021-02256-y ◽

2021 ◽

Author(s):

Ryota Matsui ◽

Noriyuki Inaki ◽

Toshikatsu Tsuji

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Grip Strength ◽

Hand Grip Strength ◽

Long Term Outcomes ◽

Hand Grip ◽

The Impact

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Reply to the Letter to the Editor: The impact of preoperative hand grip strength on the long-term outcomes after gastrectomy for advanced gastric cancer

Surgery Today ◽

10.1007/s00595-021-02301-w ◽

2021 ◽

Author(s):

Ryota Matsui ◽

Noriyuki Inaki ◽

Toshikatsu Tsuji

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Grip Strength ◽

Hand Grip Strength ◽

Long Term Outcomes ◽

Hand Grip ◽

Letter To The Editor ◽

The Impact

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Baseline lesion number as an efficacy predictive and independent prognostic factor and its joint utility with TMB for PD-1 inhibitor treatment in advanced gastric cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835921988996 ◽

2021 ◽

Vol 13 ◽

pp. 175883592198899

Author(s):

Xiao-Li Wei ◽

Jian-Ying Xu ◽

De-Shen Wang ◽

Dong-Liang Chen ◽

Chao Ren ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Advanced Gastric Cancer ◽

Tumor Size ◽

Univariate Analysis ◽

Objective Response ◽

Multivariable Analysis ◽

Tumor Burden ◽

Lesion Number ◽

The Impact

Background: We previously reported tumor mutation burden (TMB) as a potential prognostic factor for patients with advanced gastric cancer (AGC) receiving immunotherapy. We aimed to comprehensively understand the impact of tumor burden and TMB on efficacy and prognosis in immunotherapy-treated AGC patients. Methods: A total of 58 patients with refractory AGC receiving PD-1 inhibitor monotherapy from a phase Ib/II clinical trial (ClinicalTrials.gov identifier: NCT02915432) were retrospectively included. Univariate and multivariate logistical regression analyses and the Cox proportional hazards model were performed for prognostic value of baseline factors. Factors reflecting baseline tumor burden, including baseline lesion number (BLN), the maximum tumor size (MTS) and the sum of target lesion size (SLS) were analyzed. The objective response rate (ORR) and disease control rate (DCR) were compared by Chi-square test. Results: In univariate analysis, high BLN was associated with poor median progression-free survival (mPFS) [1.7 months versus 3.4 months; hazard ratio (HR), 2.696, p < 0.05] and median overall survival (mOS) (3.2 months versus 7.6 months; HR, 1.997, p < 0.05), while high TMB was a positive prognostic factor. In multivariable analysis, both BLN and TMB were independent prognostic factors for mOS (BLN: HR, 2.782, p < 0.05; TMB: HR, 0.288, p < 0.05), while MTS or SLS had no association with survival. Better ORR and DCR were observed in the low BLN group (15.4% versus 5.3%, p > 0.05; 86.96% versus 54.29%, p < 0.05). When combining BLN and TMB, the best efficacy and survival were observed in the BLNlowTMBhigh group (ORR: 37.5%, DCR: 62.5%, mPFS and mOS: not reached). The worst efficacy and survival were shown in the BNLhighTMBlow group [ORR: 0% (0/15); DCR: 13.3%; mPFS: 1.7 months; mOS: 2.7 months (all p < 0.05)]. Conclusions: BLN, rather than factors regarding baseline tumor size, is perhaps a potential predictor for benefit from immunotherapy and its combination with TMB could further risk-stratify patients with AGC receiving immunotherapy.

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Advanced Gastric Cancer: Current Treatment Landscape and a Future Outlook for Sequential and Personalized Guide: Swiss Expert Statement Article

Oncology Research and Treatment ◽

10.1159/000518107 ◽

2021 ◽

pp. 1-10

Author(s):

Alexander R. Siebenhüner ◽

Sara De Dosso ◽

Daniel Helbling ◽

Christoforos Astaras ◽

Petr Szturz ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Systemic Treatment ◽

Treatment Options ◽

Current Treatment ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Her 2 ◽

The Impact

Background: Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. Summary: Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, Epstein-Barr virus expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and <70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. Key Message: In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.

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Analysis of weight loss as a prognostic factor in patients (pts) with advanced gastric cancer from REGARD, RAINBOW and RAINFALL phase III studies.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.348 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 348-348

Author(s):

Wasat Mansoor ◽

Eric Roeland ◽

Aafia Chaudhry ◽

Ran Wei ◽

Anindya Chatterjee ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Advanced Gastric Cancer ◽

Meta Analysis ◽

Phase Iii ◽

Phase 3 ◽

Nutritional Interventions ◽

Negative Prognostic Factor ◽

Three Phase ◽

The Impact

348 Background: Maintaining weight (wt) and adequate nutrition during systemic treatment in advanced gastric cancer (G/GEJ) therapy remains a challenge. We investigated the impact of early wt-loss on survival in three phase 3 studies of ramucirumab (R); REGARD (RG), RAINBOW (RB), and RAINFALL (RF) in G/GEJ. Methods: ITT pts were categorized into 2 groups based on their body wt change from start to end of cycle 1 (C1; C = 28 days in RG, RB; C = 21 days in RF): wt-loss < 3% vs ≥3%. Univariate Cox PH models were performed in each individual study to evaluate the effects of body wt change from the start to end of C1 on OS. A pooled meta-analysis stratified by study and a sensitivity analysis of the subgroup of responders was also performed. Results: A total of 311 (RG: 212 in R+BSC; 99 in Placebo (PB)+BSC), 591 (RB: 306 in the R+Paclitaxel (P); 285 PB+P), and 562 (RF: 279 in R+Cape/Cis (CC); 283 in PB+CC) pts with body wt data during C1 were evaluated. The number of pts with wt-loss of ≥3% and < 3% are shown in Table. Pts with wt-loss < 3% during C1 experienced longer OS compared to those with wt-loss ≥3%, irrespective of treatment arms across studies (Table). In pooled treatment arms within each study, the HR for wt-loss group ( < 3% vs ≥3%) was 0.359 (95% CI = 0.254, 0.507), 0.632 (0.497, 0.804), 0.752 (0.608, 0.930) in RG, RB, RF, respectively. In the meta-analysis that combined the 3-studies, univariate Cox PH model stratified by study showed consistent effect of early wt-loss on OS regardless of treatment arm, HR ( < 3% vs ≥3%) = 0.632 (0.546, 0.732). Conclusions: Analysis from three phase 3 studies demonstrates early wt-loss ≥3% during C1 is an important negative prognostic factor for survival in gastric/GEJ cancer. Prospective studies of the relationship of weight preserving nutritional interventions on OS are warranted. Clinical trial information: NCT00917384, NCT01170663, NCT02314117. [Table: see text]

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P-171 The impact on survival of CPT-11 as third-line or later treatment in advanced gastric cancer

Annals of Oncology ◽

10.1093/annonc/mdw199.165 ◽

2016 ◽

Vol 27 ◽

pp. ii51

Author(s):

A. Makiyama ◽

K. Arimizu ◽

G. Hirano ◽

C. Makiyama ◽

Y. Matsushita ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Impact On Survival ◽

Third Line ◽

The Impact

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S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer: a cost-effectiveness analysis

10.21203/rs.3.rs-87467/v1 ◽

2020 ◽

Author(s):

Mingyang Feng ◽

Weiting Liao ◽

Yang Yang ◽

Qiu Li

Keyword(s):

Gastric Cancer ◽

Cost Effectiveness ◽

Incremental Cost ◽

Advanced Gastric Cancer ◽

Cost Effective ◽

Chinese Society ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

The Impact

Abstract Background: A multicenter, open-label, randomized, phase 3 trial (SOLAR) conducted in 62 centers across Japan and South Korea showed that S-1 plus leucovorin and oxaliplatin showed improved overall response rate, progression-free survival (PFS), and overall survival (OS) compared with S-1 plus cisplatin. This study aimed to investigate whether S-1 plus leucovorin and oxaliplatin is cost-effective compared with S-1 plus cisplatin as the first-line therapy of advanced gastric cancer from the perspective of Chinese society.Materials and methods: The clinical data for this model was derived from the SOLAR trial. Costs and utility were either derived from the standard fee database or extracted from previously published literature. A Markov model was developed to simulate the disease process of patients with advanced gastric cancer. One-way sensitivity analyses were conducted to investigate the impact of variables on the analysis model. A second-order probabilistic sensitivity analysis was performed based on 1,000 Monte-Carlo simulations.Results: S-1 plus leucovorin and oxaliplatin cohort provided an incremental 0.02 QALYs with an incremental cost of $1,527.31, compared with the S-1 plus cisplatin cohort, resulting in the incremental cost-effectiveness ratio (ICER) of $61,331.63/QALY, which beyond the willingness to pay threshold. Costs of drugs in the PFS state in both cohorts and utility of PFS state were the most influential factors in this study.Conclusion: S-1 plus leucovorin and oxaliplatin is not cost-effective compared with S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer from the Chinese society perspective.

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