- Email: [email protected]
HER2 copy number as predictor of disease-free survival in HER2-positive resectable gastric cancer
abstracts Funding: EMD Serono, Research Institute of McGill University Health Centre. Disclosure: T. Alcindor: Research grant / Funding (self): EMD Serono; Advisory / Consultancy: Astellas; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Taiho; Advisory / Consultancy: Shire; Advisory / Consultancy: BMS. All other authors have declared no conflicts of interest.
Annals of Oncology 4-courses). The 3-year OS was 58.1% in 2-courses CS, 58.1% in 4-courses CS, 48.5% in 2-courses DCS, and 71.9% in 4-courses DCS. Subgroup analyses were summarized in the table.
Table: 778P 777P
Evaluation of the introduction of primary G-CSF prophylaxis to the FLOT chemotherapy regimen
K-M. Crampton, J. Wood, H. Wong, M. McKay, A. Madi Pharmacy, The Clatterbridge Cancer Centre, Wirral, UK
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Subgroup analyses of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with 2 and 4 courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer
T. Hayashi1, T. Yoshikawa1, K. Sakamaki2, K. Nishikawa3, K. Fujitani4, K. Tanabe5, Y. Ito6, T. Matsui7, A. Miki8, T. Fukunaga9, H. Nemoto10, Y. Kimura11, N. Hirabayashi12 1 Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan, 2Graduate School of Medicine, Tokyo University, Tokyo, Japan, 3Gastrointestinal Surgery, Natinal Hospital Organization Osaka National Hospital, Osaka, Japan, 4Gastrointestinal Surgery, Osaka General Medical Center, Osaka, Japan, 5Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan, 6Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Japan, 7Surgery, Aichi Cancer Center Aichi Hospital, Okazaki, Japan, 8 Surgery, Kobe City Medical Center General Hospital, Kobe, Japan, 9Gastrointestinal Surgery, St Marianna University School of Medicine, Kawasaki, Japan, 10Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan, 11Gastrointestinal Surgery, Sakai City Medical Center, Sakai, Japan, 12Surgery, Hiroshima City Asa Citizens Hospital, Asa, Japan Background: Neoadjuvant chemotherapy is promising to improve the survival of locally advanced gastric cancer. However, optimal regimen and duration of treatment have not been established. We previously reported the primary results of COMPASS-D trial (ASCO-GI 2019). Herein, we report the results of subgroup analyses of efficacy by baseline disease characteristics and demographics. Methods: Patients with M0 and either T4 or T3 in case of junctional cancer or schirrhous type received 2 or 4 courses of cisplatin (60 mg/m2 at day 8) / S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1) / cisplatin (60 mg/m2 at day 1) / S-1 (80 mg/m2 for 14 days with 2 weeks rest) as neoadjuvant chemotherapy. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. Subgroup analysis was performed in each regimen (CS vs DCS) and duration (2 vs 4 courses), stratified by age, gender, esophageal invasion, macroscopic type, histological type, cT, and cN. Results: Between Oct 2011 and Sep 2014, 132 patients were assigned to CS (n ¼ 66; 33 in 2-courses and 33 in 4-courses) and DCS (n ¼ 66; 33 in 2-courses and 33 in
v300 | Gastrointestinal Tumours, Non-Colorectal
HR of 4-sourses (95%CI)
HR of DCS (95%CI)
Overall Age < 70 y.o. Age ¼ > 70 y.o. Male Female Esophageal invasionEsophageal invasionþ Schirrhous or large Type3 Non schirrous or large Type3 Differentiated Undiffirentiated cT3 or T4a cT4b cN0 cN þ
0.77 (0.43-1.22) 0.82 (0.45-1.52) 0.49 (0.17-1.39) 0.53 (0.27-1.05) 1.22 (0.51-2.90) 0.72 (0.40-1.31) 0.73 (0.24-2.17) 0.47 (0.22-1.00) 0.74 (0.23-2.41) 0.37 (0.08-1.66) 0.66 (0.32-1.36) 0.66 (0.38-1.17) N/A 0.77 (0.32-1.86) 0.66 (0.34-1.27)
0.80 (0.48-1.34) 0.88 (0.48-1.62) 0.68 (0.26-1.76) 0.81 (0.42-1.54) 0.79 (0.33-1.87) 0.71 (0.39-1.27) 1.06 (0.36-3.16) 0.82 (0.41-1.63) 0.50 (0.13-1.87) 0.38 (0.09-1.71) 1.24 (0.63-2.43) 0.76 (0.44-1.32) 2.33 (0.26-21.4) 0.74 (0.31-1.80) 0.87 (0.46-1.66)
Conclusions: The DCS regimen and duration 4-courses showed a beneficial tendency as a neoadjuvant setting regardless of disease characteristics and demographics. The 4courses DCS is widely applicable to future phase III study to confirm of neoadjuvant chemotherapy for locally advanced gastric cancer. Clinical trial identification: UMIN000006378. Legal entity responsible for the study: The authors. Funding: The Nongovermental Organization, Kanagawa Standard Anti-cancer Therapy Support System. Disclosure: All authors have declared no conflicts of interest.
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HER2 copy number as predictor of disease-free survival in HER2positive resectable gastric cancer
Z. Liu1, M. Shi1, S. Song1, J. Gao1, H. Li2, H. Han-Zhang2, J. Ye3 Oncology Department, The Affiliated Hospital of Qingdao University, Qingdao, China, 2 Medicine, Burning Rock Biotech, Guangzhou, China, 3Bioinformatics, Burning Rock Biotech, Guangzhou, China
1
Background: The identification of HER2 overexpression in a subset of gastric cancer (GC) patients represents a significant step forward in unveiling the molecular complexity of this disease. The predictive and prognostic value of HER2 amplification in advanced HER2 inhibitor-treated GC patients has been investigated. However, its predictive value in early stage resectable patients remains unclear. In this study we interrogated the correlation between HER2 copy number (CN) and disease-free survival (DFS). Methods: We enrolled 98 treatment-naı¨ve resectable (stage I-III) Chinese GC patients with HER2 overexpression assessed using IHC. Capture-based targeted sequencing using a panel consisting of 41 gastrointestinal cancer -related genes was performed on FFPE samples. Furthermore, we also investigated the correlation between HER2 CN and DFS. This cohort had 81 males and 17 females, with a median age of 64. 12, 62 and 24 patients had diffuse, intestinal and mixed GC respectively. Results: Of the 98 HER2-overexpressed patients assessed using IHC, 91 had HER2 CN amplification assessed using next-generation sequencing, achieving 93% concordance. In addition, 10 had concurrent HER2 missense mutations, including 4 with S310X. All patients except for two had at least one concurrent mutation. The most commonly seen concurrent mutations were TP53, EGFR and PIK3CA, occurring in 85%, 13% and 12% patients, respectively. Furthermore, 23 patients had mutations in EGFR, MET, PDGFRA or KIT, which may participate in the activation of bypass pathways. We also revealed that patients with concurrent TP53 (p ¼ 0.05) or PI3KCA (p ¼ 0.02) mutations were significantly older than patients without. Next, dichotomous analysis was performed to investigate the association between HER2 CN and DFS. Stage I patients did not undergo adjuvant chemotherapy and all stage II-III patients underwent adjuvant chemotherapy. Our study revealed that patients with high HER2 CN had a significantly shorter DFS than patients with low HER2 CN (p ¼ 0.002). Conclusions: We elucidated the mutation spectrum of HER2-amplified resectable Chinese GC patients and the association between HER2 CN and DFS. Our study revealed the predictive value of HER2 CN and allowed us to further stratify HER2-positive patients.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz247.105/5577130 by guest on 26 October 2019
Background: FLOT chemotherapy is a standard of care for patients with early gastric & gastroesophageal junction adenocarcinoma: 4 cycles pre- and 4 post-surgery. It was introduced at the Clatterbridge Cancer Centre in October 2017 following the presentation of FLOT4 trial data. Primary prophylaxis with GCSF was not part of the trial protocol but was allowed as per investigator’s discretion. As such GCSF was not included in the FLOT regimen initially in our centre. However, a significant number of patients could not proceed with their second cycle on time due to prolonged grade 3-4 neutropenia or neutropenic infection. Therefore, primary GCSF prophylaxis was introduced from day 5 of each cycle for 5 days at doses of 300 & 480 micrograms for patients with weight <70 and >70 kg, respectively. Methods: Patients were identified from chemotherapy-prescribing records and data was collected from their electronic notes. As a primary objective we compared rates of dose delay because of neutropenia before and after introducing primary GCSF prophylaxis. We also looked at other reasons for dose delay & reduction. Results: 47 patients started FLOT between October 2017 & July 2018; 41 were men and median age was 63.7 years (36-79). 2 patients had FLOT only in the adjuvant setting. In patients who started neoadjuvant FLOT, 27 patients (57.4%) went on to receive FLOT adjuvantly. 19 patients (40.4%) completed 8 cycles and the median number of cycles received was 5.6 (1-8 cycles). 13 patients had FLOT without primary GCSF prophylaxis, 61.6% of them had dose delays because of neutropenia. After the addition of primary GCSF prophylaxis, the rate of neutropenia resulting in dose delay fell to 2.9% (p ¼ 0.00). 46.8% of patients had their treatment delayed for reasons other than neutropenia with the highest rates of deferral seen for non-neutropenic infection (10.6%) and nausea & vomiting (10.6%). 31.9% of patients had their treatment dose reduced; this was most commonly for diarrhoea (10.6%) and peripheral neuropathies (8.5%). Conclusions: 61.6% of patients receiving the FLOT regimen had treatment delays because of neutropenia. Primary GCSF prophylaxis almost eliminated this problem and reduced the overall rate of dose delays. Therefore, primary GCSF prophylaxis should routinely be used with FLOT. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Subgroup
abstracts
Annals of Oncology Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Effect of neoadjuvant chemotherapy on the programmed death-1 pathway in esophageal and gastric cancer
Background: Esophageal and gastric (EG) cancers stand for a considerable amount of cancer cases and deaths worldwide. Although addition of neoadjuvant and/or adjuvant therapy has led to an improved survival in patients with resectable tumours, there is still a great unmet need for novel treatment strategies and complementary biomarkers. This study examined the effect of neoadjuvant chemotherapy on the expression of programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) in EG adenocarcinoma, as well as the associations of PD-1 and PD-L1 expression with histopathological response and clinical outcome. Methods: Immunohistochemical expression of PD-1 on tumour-infiltrating immune cells (TIC) and of PD-L1 on tumour cells (TC) and TIC was assessed on paired pretreatment biopsies, post-treatment resected primary tumours and a subset of paired lymph node metastases from a consecutive cohort of 148 patients with neoadjuvant þ/- adjuvant treated EG adenocarcinoma. Results: PD-1 expression was significantly higher in resected tumours and in lymph node metastases compared to biopsies, but the expression of PD-L1 TC and PD-L1 TIC was similar before and after neoadjuvant therapy. PD-1 expression was not associated with histopathological response or with survival. Positive PD-L1 TC expression in biopsies was significantly associated with histopathological response but not with survival, whereas positive PD-L1 TC expression in resected tumours signified a reduced overall survival. High PD-L1 TIC expression in biopsies, but not in resected tumours, was significantly associated with a prolonged overall survival. Conclusions: Expression of PD-1, but not of PD-L1, is augmented after neoadjuvant treatment. Chemotherapy may however evoke more resistant subsets of PD-L1 positive TC, thus indicating a need for alternative treatment strategies in the adjuvant setting. Legal entity responsible for the study: Lund University. Funding: SUS Stiftelse och Donationer Fru Berta Kamprads Stiftelse Vetenskapliga ra˚det, Projektmedel fo¨r forsknings- och Utvecklingsarbete. Disclosure: All authors have declared no conflicts of interest.
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A user-friendly nomogram to predict relapse-free survival (RFS) in western patients with resected gastric cancer (GC)
M. Salati1, S. Pipitone2, M. Rimini1, F. Gelsomino1, A. Casadei-Gardini1, K. Andrikou1, F.M. Schipilliti1, G. Cortesi3, L. Cassanelli1, E. Caffari1, F. Serra4, A. Ricciardolo4, N. De Ruvo4, R. Gelmini4, S. Cascinu3, A. Spallanzani3 1 Medical Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy, 2Oncologia Medica, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy, 3Department of Oncology and Hematology, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena, Italy, 4Surgical Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy Background: Despite multimodality treatment, in the Western world > 50% of GC patients relapse following curative-intent surgery and succumb to their disease. The absolute survival benefit of perioperative or adjuvant chemotherapy ranges from 6 to 15% at 5 years and must be balanced against treatment-related toxicities. Reliable tools to risk-stratify patients are lacking. The aim of this study was to build a practical tool to guide daily decision-making and clinical trial design. Methods: Data of patients undergoing curative-intent surgery for T2-4 and N-positive GC between 2008 and 2018 at the Modena Cancer Centre were retrieved. Clinicopathologic and biochemical parameters deemed of potential interest were collected. The cut-off value for continuos variables was assessed at 75 percentile. Univariate and multivariate Cox proportional-hazard models were used to assess the prognostic value of covariates. Based on the multivariate model, a nomogram to predict 2- and 3-year RFS was developed with a corresponding number of points assigned to a given magnitude of the variable. Results: A total of 157 patients were eligible for the analysis. 51% (n ¼ 80) were female and 88% (n ¼ 139) had an ECOG PS of 0-1. Only 6% of cases were gastroesophageal junction cancers. 13% (n ¼ 20), 25% (n ¼ 40), 62% (n ¼ 97) presented at diagnosis with stage I, II and III, respectively. Adjuvant chemotherapy was administered to 49% of patients. Out of 15 covariates tested, the following were independent predictors of outcome in the multivariate analysis and therefore included in the nomogram: ECOG PS (HR 2.51; p ¼ 0.006), nodal status (HR 3.04; p ¼ 0.078), angioinvasion (HR 2.62; p ¼ 0.005) and logNeutrophil/Lymphocyte ratio (HR 3.50; p < 0.001). Conclusions: We built an easy-to-use nomogram to estimate 2- and 3-year individual RFS probability in resected GC. Interestingly, this tool incorporates variables reflecting
Volume 30 | Supplement 5 | October 2019
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Efficacy and toxicity of weekly carboplatin and paclitaxel as induction or palliative treatment in advanced esophageal cancer patients
F.M. de Man, R.A.G. Van Eerden, E. Oomen-de Hoop, J.N. Veraart, N. van Doorn, L. van Doorn, A. van der Gaast, R.H.J. Mathijssen Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Background: Half of all patients with esophageal cancer present with advanced disease at diagnosis. The most optimal treatment for this group has not been identified yet. Therefore, we evaluated a weekly regimen of carboplatin for 6 cycles (area under the curve (AUC) of 4) þ paclitaxel 100mg/m2 as induction (iCT) or palliative treatment (pCT). Methods: All patients with advanced (gastro-) esophageal cancer treated with this regimen between 2002-2018 at the Erasmus MC Rotterdam were included. Patients who received radiotherapy or were treated elsewhere were excluded. Data on toxicity, response, and survival were collected from patient records. Analyses were performed in 2 groups: iCT or pCT. Median progression free survival (PFS) and median overall survival (OS) were estimated with the Kaplan-Meier method. Results: A total of 291 patients was included (iCT:122; pCT:169). Most patients had T3 carcinoma (iCT:54%; pCT:66%), and stage IV disease (iCT:42%; pCT:91%). The majority of the tumors were adenocarcinomas (iCT:50%; pCT:70%) and located at the distal esophagus (iCT:47%; pCT:73%). Incidence of severe grade 3 gastrointestinal toxicity was low (iCT:3%; pCT:5%). Grade 3 toxicity occurred mainly as hematological toxicity (iCT:71%; pCT:73%) with grade 3 neutropenia of 43% and grade 4 of 25% in both groups. Nonetheless, only 3% of patients experienced febrile neutropenia. Premature termination of the planned cycles due to toxicity occurred in 12% of the iCT group and 17% of the pCT group. Cycle delay due to toxicity occurred in 42% (iCT) and 43% (pCT) of the patients. Sensory neuropathy was low-graded and seen in 25% (iCT) and 26% (pCT) of the patients. Overall response rates were 48% (iCT) and 44% (pCT). Esophagectomy or definitive chemoradiotherapy followed in 42% of iCT, resulting in a PFS of 22.1 months (interquartile range (IQR): 12.4-114.2) and OS of 26.8 months (IQR: 15.4-91.7). For pCT, PFS was 8.2 months (IQR: 5.1-14.5) and OS 10.9 months (IQR: 6.5-18.3). Conclusions: Weekly carboplatin (AUC4) and paclitaxel (100mg/m2) as an outpatient regimen is well-tolerated and an effective induction or palliative treatment regimen for patients with locally advanced or metastatic disease. Legal entity responsible for the study: A.H.J. Mathijssen. Funding: Has not received any funding. Disclosure: R.H.J. Mathijssen: Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Cristal Therapeutics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Honoraria (institution): Servier; Honoraria (institution): Novartis; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Astellas. All other authors have declared no conflicts of interest.
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Perioperative chemotherapy with docetaxel, oxaliplatin, fluorouracil and leucovorin (FLOT) versus epirubicin, platinum and capecitabine or flourouracil (EOX/ECF) in resectable gastric or gastroesophageal junction adenocarcinoma: Safety and response data from India
T. Chawla1, R. Thambudorai2, A. Ashok3, B. Roy2, J. Ghosh4, S. Ganguly4, P. Roy5, M. Mallath4 1 Clinical Pharmacology, Tata Medical Center, Kolkata, India, 2GI-HPB Surgery, Tata Medical Center, Kolkata, India, 3Thoracic Surgery, Tata Memorial Hospital, Mumbai, India, 4Medical Oncology, Tata Medical Center, Kolkata, India, 5Pathology, Tata Medical Center, Kolkata, India Background: Gastric and GEJ cancers are one of the top four cancers in India with poor 5-year survival. Post ASCO 2017, we switched to docetaxel-based peri-operative chemotherapy (FLOT) which is the new standard of care. In this audit, we report the pathological response and toxicity of FLOT compared to our older standard (EOX/ ECF). Methods: We analysed our database of 118 patients with gastric or GEJ adenocarcinoma treated at our center from May 2011 to April 2019. 85 patients (72%) received perioperative chemotherapy with three pre-operative and three post-operative 3-week cycles of either EOX (50mg/m2 Epirubicin and 130mg/m2 Oxaliplatin on Day 1 plus 1250mg/m2 Capecitabine for 21 days) or ECF (50mg/m2 Epirubicin and 60mg/m2 Cisplatin on Day 1 plus 800mg/m2/day Fluorouracil as continuous intravenous infusion for 5 days). 33 patients (28%) received four pre-operative and four post-operative
doi:10.1093/annonc/mdz247 | v301
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M.C. Svensson1, A. Linde´n1, J. Nygaard1, C. Hedner1, B. Nodin1, D. Borg1, K. Leandersson2, K. Jirstro¨m1 1 Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden, 2Cancer Immunology, Department of Translational Medicine, Lund University, Malmo¨, Sweden, Lund University, Lund, Sweden
patients characteristics (ECOG PS), tumour aggressiveness (nodal status and angioinvasion) and immune-inflammation status (NLR). This nomogram could assist clinicians in discussing with patients prognosis and the risk-to-benefit ratio of systemic treatment as well as the design of future trials. Legal entity responsible for the study: Massimiliano Salati. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology 4-courses). The 3-year OS was 58.1% in 2-courses CS, 58.1% in 4-courses CS, 48.5% in 2-courses DCS, and 71.9% in 4-courses DCS. Subgroup analyses were summarized in the table.
Table: 778P 777P
Evaluation of the introduction of primary G-CSF prophylaxis to the FLOT chemotherapy regimen
K-M. Crampton, J. Wood, H. Wong, M. McKay, A. Madi Pharmacy, The Clatterbridge Cancer Centre, Wirral, UK
778P
Subgroup analyses of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with 2 and 4 courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer
T. Hayashi1, T. Yoshikawa1, K. Sakamaki2, K. Nishikawa3, K. Fujitani4, K. Tanabe5, Y. Ito6, T. Matsui7, A. Miki8, T. Fukunaga9, H. Nemoto10, Y. Kimura11, N. Hirabayashi12 1 Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan, 2Graduate School of Medicine, Tokyo University, Tokyo, Japan, 3Gastrointestinal Surgery, Natinal Hospital Organization Osaka National Hospital, Osaka, Japan, 4Gastrointestinal Surgery, Osaka General Medical Center, Osaka, Japan, 5Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan, 6Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Japan, 7Surgery, Aichi Cancer Center Aichi Hospital, Okazaki, Japan, 8 Surgery, Kobe City Medical Center General Hospital, Kobe, Japan, 9Gastrointestinal Surgery, St Marianna University School of Medicine, Kawasaki, Japan, 10Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan, 11Gastrointestinal Surgery, Sakai City Medical Center, Sakai, Japan, 12Surgery, Hiroshima City Asa Citizens Hospital, Asa, Japan Background: Neoadjuvant chemotherapy is promising to improve the survival of locally advanced gastric cancer. However, optimal regimen and duration of treatment have not been established. We previously reported the primary results of COMPASS-D trial (ASCO-GI 2019). Herein, we report the results of subgroup analyses of efficacy by baseline disease characteristics and demographics. Methods: Patients with M0 and either T4 or T3 in case of junctional cancer or schirrhous type received 2 or 4 courses of cisplatin (60 mg/m2 at day 8) / S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1) / cisplatin (60 mg/m2 at day 1) / S-1 (80 mg/m2 for 14 days with 2 weeks rest) as neoadjuvant chemotherapy. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. Subgroup analysis was performed in each regimen (CS vs DCS) and duration (2 vs 4 courses), stratified by age, gender, esophageal invasion, macroscopic type, histological type, cT, and cN. Results: Between Oct 2011 and Sep 2014, 132 patients were assigned to CS (n ¼ 66; 33 in 2-courses and 33 in 4-courses) and DCS (n ¼ 66; 33 in 2-courses and 33 in
v300 | Gastrointestinal Tumours, Non-Colorectal
HR of 4-sourses (95%CI)
HR of DCS (95%CI)
Overall Age < 70 y.o. Age ¼ > 70 y.o. Male Female Esophageal invasionEsophageal invasionþ Schirrhous or large Type3 Non schirrous or large Type3 Differentiated Undiffirentiated cT3 or T4a cT4b cN0 cN þ
0.77 (0.43-1.22) 0.82 (0.45-1.52) 0.49 (0.17-1.39) 0.53 (0.27-1.05) 1.22 (0.51-2.90) 0.72 (0.40-1.31) 0.73 (0.24-2.17) 0.47 (0.22-1.00) 0.74 (0.23-2.41) 0.37 (0.08-1.66) 0.66 (0.32-1.36) 0.66 (0.38-1.17) N/A 0.77 (0.32-1.86) 0.66 (0.34-1.27)
0.80 (0.48-1.34) 0.88 (0.48-1.62) 0.68 (0.26-1.76) 0.81 (0.42-1.54) 0.79 (0.33-1.87) 0.71 (0.39-1.27) 1.06 (0.36-3.16) 0.82 (0.41-1.63) 0.50 (0.13-1.87) 0.38 (0.09-1.71) 1.24 (0.63-2.43) 0.76 (0.44-1.32) 2.33 (0.26-21.4) 0.74 (0.31-1.80) 0.87 (0.46-1.66)
Conclusions: The DCS regimen and duration 4-courses showed a beneficial tendency as a neoadjuvant setting regardless of disease characteristics and demographics. The 4courses DCS is widely applicable to future phase III study to confirm of neoadjuvant chemotherapy for locally advanced gastric cancer. Clinical trial identification: UMIN000006378. Legal entity responsible for the study: The authors. Funding: The Nongovermental Organization, Kanagawa Standard Anti-cancer Therapy Support System. Disclosure: All authors have declared no conflicts of interest.
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HER2 copy number as predictor of disease-free survival in HER2positive resectable gastric cancer
Z. Liu1, M. Shi1, S. Song1, J. Gao1, H. Li2, H. Han-Zhang2, J. Ye3 Oncology Department, The Affiliated Hospital of Qingdao University, Qingdao, China, 2 Medicine, Burning Rock Biotech, Guangzhou, China, 3Bioinformatics, Burning Rock Biotech, Guangzhou, China
1
Background: The identification of HER2 overexpression in a subset of gastric cancer (GC) patients represents a significant step forward in unveiling the molecular complexity of this disease. The predictive and prognostic value of HER2 amplification in advanced HER2 inhibitor-treated GC patients has been investigated. However, its predictive value in early stage resectable patients remains unclear. In this study we interrogated the correlation between HER2 copy number (CN) and disease-free survival (DFS). Methods: We enrolled 98 treatment-naı¨ve resectable (stage I-III) Chinese GC patients with HER2 overexpression assessed using IHC. Capture-based targeted sequencing using a panel consisting of 41 gastrointestinal cancer -related genes was performed on FFPE samples. Furthermore, we also investigated the correlation between HER2 CN and DFS. This cohort had 81 males and 17 females, with a median age of 64. 12, 62 and 24 patients had diffuse, intestinal and mixed GC respectively. Results: Of the 98 HER2-overexpressed patients assessed using IHC, 91 had HER2 CN amplification assessed using next-generation sequencing, achieving 93% concordance. In addition, 10 had concurrent HER2 missense mutations, including 4 with S310X. All patients except for two had at least one concurrent mutation. The most commonly seen concurrent mutations were TP53, EGFR and PIK3CA, occurring in 85%, 13% and 12% patients, respectively. Furthermore, 23 patients had mutations in EGFR, MET, PDGFRA or KIT, which may participate in the activation of bypass pathways. We also revealed that patients with concurrent TP53 (p ¼ 0.05) or PI3KCA (p ¼ 0.02) mutations were significantly older than patients without. Next, dichotomous analysis was performed to investigate the association between HER2 CN and DFS. Stage I patients did not undergo adjuvant chemotherapy and all stage II-III patients underwent adjuvant chemotherapy. Our study revealed that patients with high HER2 CN had a significantly shorter DFS than patients with low HER2 CN (p ¼ 0.002). Conclusions: We elucidated the mutation spectrum of HER2-amplified resectable Chinese GC patients and the association between HER2 CN and DFS. Our study revealed the predictive value of HER2 CN and allowed us to further stratify HER2-positive patients.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz247.105/5577130 by guest on 26 October 2019
Background: FLOT chemotherapy is a standard of care for patients with early gastric & gastroesophageal junction adenocarcinoma: 4 cycles pre- and 4 post-surgery. It was introduced at the Clatterbridge Cancer Centre in October 2017 following the presentation of FLOT4 trial data. Primary prophylaxis with GCSF was not part of the trial protocol but was allowed as per investigator’s discretion. As such GCSF was not included in the FLOT regimen initially in our centre. However, a significant number of patients could not proceed with their second cycle on time due to prolonged grade 3-4 neutropenia or neutropenic infection. Therefore, primary GCSF prophylaxis was introduced from day 5 of each cycle for 5 days at doses of 300 & 480 micrograms for patients with weight <70 and >70 kg, respectively. Methods: Patients were identified from chemotherapy-prescribing records and data was collected from their electronic notes. As a primary objective we compared rates of dose delay because of neutropenia before and after introducing primary GCSF prophylaxis. We also looked at other reasons for dose delay & reduction. Results: 47 patients started FLOT between October 2017 & July 2018; 41 were men and median age was 63.7 years (36-79). 2 patients had FLOT only in the adjuvant setting. In patients who started neoadjuvant FLOT, 27 patients (57.4%) went on to receive FLOT adjuvantly. 19 patients (40.4%) completed 8 cycles and the median number of cycles received was 5.6 (1-8 cycles). 13 patients had FLOT without primary GCSF prophylaxis, 61.6% of them had dose delays because of neutropenia. After the addition of primary GCSF prophylaxis, the rate of neutropenia resulting in dose delay fell to 2.9% (p ¼ 0.00). 46.8% of patients had their treatment delayed for reasons other than neutropenia with the highest rates of deferral seen for non-neutropenic infection (10.6%) and nausea & vomiting (10.6%). 31.9% of patients had their treatment dose reduced; this was most commonly for diarrhoea (10.6%) and peripheral neuropathies (8.5%). Conclusions: 61.6% of patients receiving the FLOT regimen had treatment delays because of neutropenia. Primary GCSF prophylaxis almost eliminated this problem and reduced the overall rate of dose delays. Therefore, primary GCSF prophylaxis should routinely be used with FLOT. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Subgroup
abstracts
Annals of Oncology Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Effect of neoadjuvant chemotherapy on the programmed death-1 pathway in esophageal and gastric cancer
Background: Esophageal and gastric (EG) cancers stand for a considerable amount of cancer cases and deaths worldwide. Although addition of neoadjuvant and/or adjuvant therapy has led to an improved survival in patients with resectable tumours, there is still a great unmet need for novel treatment strategies and complementary biomarkers. This study examined the effect of neoadjuvant chemotherapy on the expression of programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) in EG adenocarcinoma, as well as the associations of PD-1 and PD-L1 expression with histopathological response and clinical outcome. Methods: Immunohistochemical expression of PD-1 on tumour-infiltrating immune cells (TIC) and of PD-L1 on tumour cells (TC) and TIC was assessed on paired pretreatment biopsies, post-treatment resected primary tumours and a subset of paired lymph node metastases from a consecutive cohort of 148 patients with neoadjuvant þ/- adjuvant treated EG adenocarcinoma. Results: PD-1 expression was significantly higher in resected tumours and in lymph node metastases compared to biopsies, but the expression of PD-L1 TC and PD-L1 TIC was similar before and after neoadjuvant therapy. PD-1 expression was not associated with histopathological response or with survival. Positive PD-L1 TC expression in biopsies was significantly associated with histopathological response but not with survival, whereas positive PD-L1 TC expression in resected tumours signified a reduced overall survival. High PD-L1 TIC expression in biopsies, but not in resected tumours, was significantly associated with a prolonged overall survival. Conclusions: Expression of PD-1, but not of PD-L1, is augmented after neoadjuvant treatment. Chemotherapy may however evoke more resistant subsets of PD-L1 positive TC, thus indicating a need for alternative treatment strategies in the adjuvant setting. Legal entity responsible for the study: Lund University. Funding: SUS Stiftelse och Donationer Fru Berta Kamprads Stiftelse Vetenskapliga ra˚det, Projektmedel fo¨r forsknings- och Utvecklingsarbete. Disclosure: All authors have declared no conflicts of interest.
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A user-friendly nomogram to predict relapse-free survival (RFS) in western patients with resected gastric cancer (GC)
M. Salati1, S. Pipitone2, M. Rimini1, F. Gelsomino1, A. Casadei-Gardini1, K. Andrikou1, F.M. Schipilliti1, G. Cortesi3, L. Cassanelli1, E. Caffari1, F. Serra4, A. Ricciardolo4, N. De Ruvo4, R. Gelmini4, S. Cascinu3, A. Spallanzani3 1 Medical Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy, 2Oncologia Medica, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy, 3Department of Oncology and Hematology, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena, Italy, 4Surgical Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy Background: Despite multimodality treatment, in the Western world > 50% of GC patients relapse following curative-intent surgery and succumb to their disease. The absolute survival benefit of perioperative or adjuvant chemotherapy ranges from 6 to 15% at 5 years and must be balanced against treatment-related toxicities. Reliable tools to risk-stratify patients are lacking. The aim of this study was to build a practical tool to guide daily decision-making and clinical trial design. Methods: Data of patients undergoing curative-intent surgery for T2-4 and N-positive GC between 2008 and 2018 at the Modena Cancer Centre were retrieved. Clinicopathologic and biochemical parameters deemed of potential interest were collected. The cut-off value for continuos variables was assessed at 75 percentile. Univariate and multivariate Cox proportional-hazard models were used to assess the prognostic value of covariates. Based on the multivariate model, a nomogram to predict 2- and 3-year RFS was developed with a corresponding number of points assigned to a given magnitude of the variable. Results: A total of 157 patients were eligible for the analysis. 51% (n ¼ 80) were female and 88% (n ¼ 139) had an ECOG PS of 0-1. Only 6% of cases were gastroesophageal junction cancers. 13% (n ¼ 20), 25% (n ¼ 40), 62% (n ¼ 97) presented at diagnosis with stage I, II and III, respectively. Adjuvant chemotherapy was administered to 49% of patients. Out of 15 covariates tested, the following were independent predictors of outcome in the multivariate analysis and therefore included in the nomogram: ECOG PS (HR 2.51; p ¼ 0.006), nodal status (HR 3.04; p ¼ 0.078), angioinvasion (HR 2.62; p ¼ 0.005) and logNeutrophil/Lymphocyte ratio (HR 3.50; p < 0.001). Conclusions: We built an easy-to-use nomogram to estimate 2- and 3-year individual RFS probability in resected GC. Interestingly, this tool incorporates variables reflecting
Volume 30 | Supplement 5 | October 2019
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Efficacy and toxicity of weekly carboplatin and paclitaxel as induction or palliative treatment in advanced esophageal cancer patients
F.M. de Man, R.A.G. Van Eerden, E. Oomen-de Hoop, J.N. Veraart, N. van Doorn, L. van Doorn, A. van der Gaast, R.H.J. Mathijssen Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Background: Half of all patients with esophageal cancer present with advanced disease at diagnosis. The most optimal treatment for this group has not been identified yet. Therefore, we evaluated a weekly regimen of carboplatin for 6 cycles (area under the curve (AUC) of 4) þ paclitaxel 100mg/m2 as induction (iCT) or palliative treatment (pCT). Methods: All patients with advanced (gastro-) esophageal cancer treated with this regimen between 2002-2018 at the Erasmus MC Rotterdam were included. Patients who received radiotherapy or were treated elsewhere were excluded. Data on toxicity, response, and survival were collected from patient records. Analyses were performed in 2 groups: iCT or pCT. Median progression free survival (PFS) and median overall survival (OS) were estimated with the Kaplan-Meier method. Results: A total of 291 patients was included (iCT:122; pCT:169). Most patients had T3 carcinoma (iCT:54%; pCT:66%), and stage IV disease (iCT:42%; pCT:91%). The majority of the tumors were adenocarcinomas (iCT:50%; pCT:70%) and located at the distal esophagus (iCT:47%; pCT:73%). Incidence of severe grade 3 gastrointestinal toxicity was low (iCT:3%; pCT:5%). Grade 3 toxicity occurred mainly as hematological toxicity (iCT:71%; pCT:73%) with grade 3 neutropenia of 43% and grade 4 of 25% in both groups. Nonetheless, only 3% of patients experienced febrile neutropenia. Premature termination of the planned cycles due to toxicity occurred in 12% of the iCT group and 17% of the pCT group. Cycle delay due to toxicity occurred in 42% (iCT) and 43% (pCT) of the patients. Sensory neuropathy was low-graded and seen in 25% (iCT) and 26% (pCT) of the patients. Overall response rates were 48% (iCT) and 44% (pCT). Esophagectomy or definitive chemoradiotherapy followed in 42% of iCT, resulting in a PFS of 22.1 months (interquartile range (IQR): 12.4-114.2) and OS of 26.8 months (IQR: 15.4-91.7). For pCT, PFS was 8.2 months (IQR: 5.1-14.5) and OS 10.9 months (IQR: 6.5-18.3). Conclusions: Weekly carboplatin (AUC4) and paclitaxel (100mg/m2) as an outpatient regimen is well-tolerated and an effective induction or palliative treatment regimen for patients with locally advanced or metastatic disease. Legal entity responsible for the study: A.H.J. Mathijssen. Funding: Has not received any funding. Disclosure: R.H.J. Mathijssen: Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Cristal Therapeutics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Honoraria (institution): Servier; Honoraria (institution): Novartis; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Astellas. All other authors have declared no conflicts of interest.
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Perioperative chemotherapy with docetaxel, oxaliplatin, fluorouracil and leucovorin (FLOT) versus epirubicin, platinum and capecitabine or flourouracil (EOX/ECF) in resectable gastric or gastroesophageal junction adenocarcinoma: Safety and response data from India
T. Chawla1, R. Thambudorai2, A. Ashok3, B. Roy2, J. Ghosh4, S. Ganguly4, P. Roy5, M. Mallath4 1 Clinical Pharmacology, Tata Medical Center, Kolkata, India, 2GI-HPB Surgery, Tata Medical Center, Kolkata, India, 3Thoracic Surgery, Tata Memorial Hospital, Mumbai, India, 4Medical Oncology, Tata Medical Center, Kolkata, India, 5Pathology, Tata Medical Center, Kolkata, India Background: Gastric and GEJ cancers are one of the top four cancers in India with poor 5-year survival. Post ASCO 2017, we switched to docetaxel-based peri-operative chemotherapy (FLOT) which is the new standard of care. In this audit, we report the pathological response and toxicity of FLOT compared to our older standard (EOX/ ECF). Methods: We analysed our database of 118 patients with gastric or GEJ adenocarcinoma treated at our center from May 2011 to April 2019. 85 patients (72%) received perioperative chemotherapy with three pre-operative and three post-operative 3-week cycles of either EOX (50mg/m2 Epirubicin and 130mg/m2 Oxaliplatin on Day 1 plus 1250mg/m2 Capecitabine for 21 days) or ECF (50mg/m2 Epirubicin and 60mg/m2 Cisplatin on Day 1 plus 800mg/m2/day Fluorouracil as continuous intravenous infusion for 5 days). 33 patients (28%) received four pre-operative and four post-operative
doi:10.1093/annonc/mdz247 | v301
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz247.105/5577130 by guest on 26 October 2019
M.C. Svensson1, A. Linde´n1, J. Nygaard1, C. Hedner1, B. Nodin1, D. Borg1, K. Leandersson2, K. Jirstro¨m1 1 Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden, 2Cancer Immunology, Department of Translational Medicine, Lund University, Malmo¨, Sweden, Lund University, Lund, Sweden
patients characteristics (ECOG PS), tumour aggressiveness (nodal status and angioinvasion) and immune-inflammation status (NLR). This nomogram could assist clinicians in discussing with patients prognosis and the risk-to-benefit ratio of systemic treatment as well as the design of future trials. Legal entity responsible for the study: Massimiliano Salati. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.