P-354 Association between tumor regression with tumor location and inflammatory biomarkers in patients with resectable gastric cancer and gastroesophageal junction cancer who underwent perioperative chemotherapy: Multicentric data from Peru

4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.

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Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): Results of nivolumab plus chemotherapy (NIVO+chemo) versus chemo from CheckMate 649.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.167 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 167-167

Author(s):

Elena Elimova ◽

Lucjan Wyrwicz ◽

Steven I. Blum ◽

Hong Xiao ◽

Mingshun Li ◽

...

Keyword(s):

Gastric Cancer ◽

Gastroesophageal Junction ◽

Well Being ◽

Primary Analysis ◽

Open Label ◽

Cox Models ◽

Study Objective ◽

Gastroesophageal Junction Cancer ◽

Patient Reported ◽

Mean Differences

167 Background: CheckMate 649 (NCT02872116) is a randomized, open label phase 3 study in first line (1L) treatment of pts with advanced GC/GEJC/EAC. Primary analysis results showed statistically significant improvement in overall survival (OS) for NIVO+chemo vs. chemo in all randomized pts. We present HRQOL results for these pts, included as an exploratory study objective. Methods: HRQOL was assessed using EQ-5D-3L (EQ-5D) and Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga). Assessments were performed at baseline (BL), every 6 weeks during treatment and during follow-up. Change from BL EQ-5D Visual Analog Scale (VAS), Utility Index (UI) and FACT-Ga scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement was based on prespecified meaningful change thresholds. Results: 1581 pts were randomized to NIVO+chemo (n = 789) or chemo (n = 792). Among 1359 pts with BL and post-BL patient-reported outcomes (NIVO+chemo, n = 693; chemo, n = 666), BL scores for FACT-Ga total were similar between treatment groups. Least squares mean differences from BL favored NIVO+chemo at most visits for EQ-5D, FACT-Ga total, and Gastric Cancer Subscale (GaCS), and were comparable for other subscales (not shown). TTI generally favored NIVO+chemo (most HR > 1) but was not significantly different between arms. TTSD was longer in NIVO+chemo arm compared with chemo alone (all HRs < 1), except for Emotional Well-Being (WB); only GaCS and FACT-Ga total were significantly different between arms. TuDD showed statistically significant delays in deterioration (HR with CI < 1) for all scores expect Social WB. Conclusions: Compared with chemo alone, the addition of NIVO to chemo maintained HRQoL with a decreased risk of symptom deterioration in patients with previously untreated advanced or metastatic GC/GEJC/EAC. Together with improved OS, these data support NIVO+chemo as a new 1L standard treatment for GC/GEJC/EAC. Clinical trial information: NCT02872116. [Table: see text]

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Efficacy and Safety of FLOT regimen vs. DCF, FOLFOX, and ECF regimens as Perioperative Chemotherapy Treatments for Resectable Gastric Cancer Patients

10.1101/2021.01.26.21250550 ◽

2021 ◽

Author(s):

Pegah Farrokhi ◽

Alireza Sadeghi ◽

Mehran sharifi ◽

Payam Dadvand ◽

Rachel Riechelmann ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

Progression Free Survival ◽

R0 Resection ◽

P Value ◽

Perioperative Chemotherapy ◽

Resectable Gastric Cancer ◽

Gastric Cancer Patients

AbstractAimThis study aimed to evaluate and compare the efficacy and toxicity of common regimens used as perioperative chemotherapy including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.Material and MethodsThis retrospective cohort study was based on 152 eligible gastric cancer patients recruited in a tertiary oncology hospital in Isfahan, Iran (2014-2019). All resectable gastric cancer patients who had received one of the four chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least one year (up to five years) were included. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint. Cox -regression models were used applied to estimate OS and PFS time, controlled for relevant covariates.ResultsOf included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 25 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 052). The median OS of the FLOT regimen was not reachable in Kaplan-Meier analysis and the median OS was 28, 26, and 23 months for DCF, FOLOFX, and ECF regimens, respectively. On the other hand, a median PFS of 25, 17, 15, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank = 0. 021). FLOT regimen showed 84. 4% ORR which was notably higher than other groups (p-value<0. 01).ConclusionsFor resectable gastric cancer patients, the perioperative FLOT regimen seemed to lead to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered as the optimal option for managing resectable gastric cancer patients.

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Poor compliance with perioperative chemotherapy for resectable gastric cancer and its impact on survival

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2019.03.040 ◽

2019 ◽

Vol 45 (10) ◽

pp. 1926-1933 ◽

Cited By ~ 1

Author(s):

Margreet van Putten ◽

Valery E.P.P. Lemmens ◽

Hanneke W.M. van Laarhoven ◽

Hans F.M. Pruijt ◽

Grard A.P. Nieuwenhuijzen ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Compliance ◽

Perioperative Chemotherapy ◽

Impact On Survival ◽

Resectable Gastric Cancer

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Correction to: Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer

Gastric Cancer ◽

10.1007/s10120-019-01021-y ◽

2019 ◽

Vol 23 (1) ◽

pp. 142-142

Author(s):

Ian Chau ◽

Dung T. Le ◽

Patrick A. Ott ◽

Beata Korytowsky ◽

Hannah Le ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

Real World ◽

Gastroesophageal Junction ◽

Gastroesophageal Junction Cancer

ping real-world comparators for

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Towards Personalization in the Curative Treatment of Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.614907 ◽

2020 ◽

Vol 10 ◽

Author(s):

Astrid E. Slagter ◽

Marieke A. Vollebergh ◽

Edwin P. M. Jansen ◽

Johanna W. van Sandick ◽

Annemieke Cats ◽

...

Keyword(s):

Gastric Cancer ◽

Treatment Options ◽

Treatment Strategies ◽

Standard Of Care ◽

Molecular Characteristics ◽

Perioperative Chemotherapy ◽

Current Standard ◽

Common Cancer ◽

Resectable Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide and has a high mortality rate. In the last decades, treatment strategy has shifted from an exclusive surgical approach to a multidisciplinary strategy. Treatment options for patients with resectable gastric cancer as recommended by different worldwide guidelines, include perioperative chemotherapy, pre- or postoperative chemoradiotherapy and postoperative chemotherapy. Although gastric cancer is a heterogeneous disease with respect to patient-, tumor-, and molecular characteristics, the current standard of care is still according to a one-size-fits-all approach. In this review, we discuss the background of the different treatment strategies in resectable gastric cancer including the current standard, the specific role of radiotherapy, and describe the current areas of research and potential strategies for personalization of therapy.

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1469P The humanistic burden reported by patients with unresectable locally advanced or metastatic (adv/met) gastric cancer (GC), gastroesophageal junction cancer (GEJC) and esophageal adenocarcinoma (EAC): An international real-world survey

Annals of Oncology ◽

10.1016/j.annonc.2020.08.1975 ◽

2020 ◽

Vol 31 ◽

pp. S918

Author(s):

J.P. Hall ◽

K. Khela ◽

R. Moon ◽

C. Middleton-Dalby ◽

D. Bertwistle ◽

...

Keyword(s):

Gastric Cancer ◽

Esophageal Adenocarcinoma ◽

Real World ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Gastroesophageal Junction Cancer ◽

World Survey ◽

Humanistic Burden

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The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis

Cancers ◽

10.3390/cancers11010080 ◽

2019 ◽

Vol 11 (1) ◽

pp. 80 ◽

Cited By ~ 8

Author(s):

Tom van den Ende ◽

Emil ter Veer ◽

Mélanie Machiels ◽

Rosa Mali ◽

Frank Abe Nijenhuis ◽

...

Keyword(s):

Gastric Cancer ◽

Curative Resection ◽

Meta Analysis ◽

Treatment Strategies ◽

Disease Free Survival ◽

Perioperative Chemotherapy ◽

Curative Intent ◽

Radio Therapy ◽

Credible Intervals ◽

Resectable Gastric Cancer

Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38–0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58–1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28–0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.

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Significance of accurate HER2 testing as a new biomarker in advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.106 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 106-106

Author(s):

Tetsuya Kusumoto ◽

Hajime Ohtsu ◽

Hiroyuki Kawano ◽

Koji Ando ◽

Satoshi Ida ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Gastroesophageal Junction ◽

Tumor Biology ◽

Japanese Patients ◽

Her2 Expression ◽

Her2 Positive ◽

Her2 Testing ◽

Gastroesophageal Junction Cancer ◽

Her2 Heterogeneity

106 Background: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2)-positive advanced or recurrent gastric or gastroesophageal junction cancer, which demonstrated that trastuzumab plus chemotherapy improved overall survival in the overall population (hazard ratio 0.74). HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity and incomplete membrane staining. The aim of the present study was to evaluate the frequency of HER2-positive cases by application of the standard criteria in Japanese patients with advanced gastric cancer (AGC) and to investigate the relationships between HER2 expression and therapeutic responses. Methods: A total of 199 tumor samples were assessed for HER2 expression both by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH). HER2-positive status was defined as IHC2+ and FISH-positive or IHC3+. Objective responses were evaluated in the patients with AGC who were treated with chemotherapy plus trastuzumab or chemotherapy alone based on the HER2 expression status. Results: HER2-positive tumors were identified in 12 patients (5.5%), less than 28.1% in the Japanese subgroup analyses of ToGA study. The positive rates varied with histological type; 14%, 5.3% and 0.95% in the well, moderately and poorly differentiated adenocarcinoma, respectively. Although high concordance between the results of IHC and FISH in all samples was found, IHC2+ samples retested here showed FISH-negative. Of all 10 patients with AGC, 3 patients with HER2-positive tumor were treated with capecitabine/cisplatin plus trastuzumab, and partial response was found in 2 cases; response rates were 67%. Conclusions: Specific consideration and scoring modification are required before embarking on HER2 testing in gastric cancer. Accurate and reliable HER2 testing and scoring will allow appropriate selection of patients eligible for treatment with trastuzumab.

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