TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): An analysis of the TAGS study

abstracts Oba: Honoraria (self): Eisai Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Daiichi-Sankyo Pharmaceutical Co., Ltd.; Honoraria (self): Asahi Kasei Pharma Corp.; Advisory / Consultancy: Takeda Pharmaceuticals, Co., Ltd.; Advisory / Consultancy: Ono Pharmaceutical Co., Ltd. Y. Yamada: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Nippon Kayaku; Honoraria (self): Eli Lilly; Honoraria (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi-Sankyo. Y. Sakata: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Advisory / Consultancy: Yakult Honsha. M. Takeuchi: Advisory / Consultancy: Hisamitsu Pharmaceutical; Advisory / Consultancy: Kowa; Advisory / Consultancy: Shionogi; Advisory / Consultancy: AbbVie. M. Fujii: Travel / Accommodation / Expenses: Taiho Pharmaceutical Co. Ltd.; Travel / Accommodation / Expenses: Japan Clinical Cancer Research Organization. All other authors have declared no conflicts of interest.

A phase Ib study of oraxol in combination with ramucirumab in patients with gastric or esophageal cancers who failed previous chemotherapy

M.H. Chen1, Y. Chao1, L. Tenner2, N.A. Hung3, D. Cutler4, D. Kramer4, M-F.R. Kwan4, C-T. Hung5 1 Deparment of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, 2Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA, 3University of Otago, University of Otago, Dunedin, New Zealand, 4 Athenex Inc, Buffalo, NY, USA, 5Zenith Technology Corporation Limited, Zenith Technology Corporation Limited, Dunedin, New Zealand Background: Oraxol consists of oral paclitaxel administered with the novel P-glycoprotein inhibitor HM30181A which enables the oral absorption of paclitaxel. Ramucirumab (RAM) þ intravenous paclitaxel is FDA approved 2nd line treatment of gastric cancer. Oraxol 200mg/m2 days 1-3, weekly has similar exposure to weekly paclitaxel 80/m2 intravenously. This study was to determine the maximum tolerated dose (MTD) of Oraxol þ RAM. Methods: 17 patients with gastric or esophageal cancers who failed prior fluoropyrimidine or platinum containing chemotherapies were studied. Dose escalation followed the standard 3 þ 3 design: Cohort 1: Oraxol 200mg/m2 days 1-3, weekly. Cohort 2: Oraxol 250mg/m2 days 1-3, weekly. Cohort 3: Oraxol 300mg/m2 days 1-3, weekly. RAM 8 mg/kg IV every 2 weeks was co-administered in all patients. Dose limiting toxicity (DLT) were assessed by week 4. Adverse events (AEs) were assessed per CTCAE v4.03 and response by RECIST v1.1. Results: Cohort 1: One febrile neutropenia (DLT) occurred in 6 patients. Partial response (PR)¼2/6, stable disease (SD)¼1/6 and progressive disease (PD)¼3/6. Cohort 2: One grade-3 neutropenia with treatment delay (DLT) occurred in 7 pts. PR ¼ 3/6 and PD ¼ 3/6 in 6 evaluable patients. Cohort 3: Two DLT (febrile neutropenia and grade-3 gastric hemorrhage) occurred in 3 patients. The MTD of Oraxol was 300mg/m2 days 1-3, weekly in combination with RAM. All patients in this study had complete recovery of their DLT. Oraxol PK did not increase significantly in Cohort-2 and Cohort-3. Conclusions: Based on the lack of significant increase in exposure to Oraxol at higher doses, with similar efficacy and DLT in Cohorts 1 and 2, an extension study using Oraxol 200mg/m2 Days 1-3, weekly þ Ramucirumab 8 mg/kg every 2 weeks as in Cohort-1 is initiated. Clinical trial identification: NCT02970539. Legal entity responsible for the study: Athenex Inc. Funding: Athenex Inc. Disclosure: All authors have declared no conflicts of interest.

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Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): An analysis of the TAGS study

M. Alsina1, J. Tabernero2, H-T. Arkenau3, M. Squadroni4, T. Doi5, C. Faustino6, M. Ghidini7, W. Mansoor8, K. Shitara9, E. Van Cutsem10, N. Causse-Amellal11, C. Leger12, D. Skanji13, D. Ilson14 1 Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain, 2 Oncology, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, 3SCRI, Sarah Cannon Research Institute SCRI UK, London, UK, 4 Oncologia Medica, Humanitas Gavazzeni, Bergamo, Italy, 5Department of Experimental Therapeutics, National Cancer Center Hospital East, Chiba, Japan, 6 Oncologia Medica, Instituto Portugues de Oncologia Centro do Porto(IPO-Porto), Porto, Portugal, 7Oncology, Istituti Ospitalieri di Cremona, Cremona, Italy, 8Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK, 9Experimental Therapeutics (and Gastrointestinal Oncology), National Cancer Center Hospital, Kashiwa, Japan, 10Internal Medicine, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium, 11Centre for Therapeutic Innovation, Servier, Suresnes, France, 12 Centre for Therapeutic Innovation, Servier, Suresnes, France, 13Statistics Department, Servier, Suresnes, France, 14Medical Oncology, Memorial Sloan Kettering, New York City, NY, USA Background: TAGS, a randomised, double-blind, phase III study, showed that FTD/ TPI significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo in heavily pretreated mGC patients (pts) receiving best

v308 | Gastrointestinal Tumours, Non-Colorectal

supportive care. The aim of this analysis was to evaluate the effects of FTP/TPI in the European subpopulation of TAGS. Methods: TAGS enrolled pts with histologically confirmed, non-resectable mGC, Eastern Cooperative Oncology Group (ECOG) performance status 0/1, and 2 prior chemotherapy regimens. Pts were randomised 2:1 to FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 every 28 days) or placebo. Primary endpoint was OS. Secondary endpoints included PFS, time to deterioration (TTD) of ECOG and safety; 507 pts were randomised to FTD/TPI (n ¼ 337) or placebo (n ¼ 170). Median follow-up was 10.7 months. Results: 277 pts (mean age 63.0 years; 75% male) were enrolled from 64 sites in Europe. Baseline characteristics were balanced between groups; 120 (67%) and 63 (65%) of pts in FTD/TPI and placebo groups had received 3 regimens of prior systemic therapy. FTP/TPI significantly prolonged OS (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.44-0.78), PFS (HR 0.46, 95% CI 0.35–0.61) and TTD to ECOG (HR 0.59, 95% CI 0.45–0.78; Table) compared with placebo. FTD/TPI had a predictable and manageable safety profile. Treatment-emergent adverse events (TEAEs) were reported in 172/ 180 (96%) FTD/TPI-treated and 92/97 (96%) placebo-treated pts. Efficacy and safety in European population of TAGS.

Table: 801P

Efficacy outcomes, median (95% CI) OS PFS TTD of ECOG TEAEs, n (%) Any Serious Grade 3 Treatment-related Leading to dose modification Leading to treatment discontinuation Leading to death

FTD/TPI (n ¼ 180)

Placebo (n ¼ 97)

HR (95% CI)

P-value (2-sided)

5.45 (4.34– 6.21) 1.94 (1.91– 2.50) 3.84 (2.89– 4.50)

3.15 (2.43– 3.58) 1.77 (1.74– 1.87) 2.10 (1.87– 2.53)

0.59 (0.44– 0.78) 0.46 (0.35– 0.61) 0.59 (0.45– 0.78)

0.0002

172 (96.1) 79 (44.1) 143 (79.9) 140 (78.2) 107 (59.8)

92 (95.8) 49 (51.0) 62 (64.6) 55 (57.3) 26 (27.1)

24 (13.4)

19 (19.8)

19 (10.6)

14 (14.6)

<0.0001 0.0001

Conclusions: FTD/TPI was effective and well tolerated in European patients, consistent with the overall population of TAGS. Clinical trial identification: NCT02500043. Editorial acknowledgement: Simone Tait of Springer Healthcare Communications, funded by Institut de Recherches Internationales Servier. Legal entity responsible for the study: Taiho Oncology and Taiho Pharmaceutical. Funding: Taiho Oncology and Taiho Pharmaceutical. Disclosure: M. Alsina: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Laboratoire Servier; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Merck. J. Tabernero: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Chugai Pharma; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Taiho pharmaceutical; Advisory / Consultancy: Takeda; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Array Biopharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Servier. M. Squadroni: Research grant / Funding (self): Taiho Pharmaceutical; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Ipsen. T. Doi: Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Chugai Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Kyowa Hakko Kirin; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Daiichi Sankyo; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sumitomo Dainippon; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho Pharmaceutical; Research grant / Funding (self): Novartis; Research grant / Funding (self): Merck Serono; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): MSD; Research grant / Funding (self): Janssen; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Takeda; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Lilly; Research grant / Funding (self): Celgene; Research grant / Funding (self): BMS; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Quintiles. C. Faustino:

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Annals of Oncology

abstracts

Annals of Oncology

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 ¼ 0.030). Conclusions: Apatinib 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 identification: AHEAD-G202 (NCT02668380). Editorial acknowledgement: Elsevier Language Editing Services. Legal entity responsible for the study: The author. Funding: Jiangsu HengRui Medcine Co., Ltd.; 2016 PUMCH Science Fund for Junior Faculty (Pumch-2016-1.13); Chinese Anti-cancer Association (CORP-143-09). Disclosure: The author has declared no conflicts of interest.

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Clinical experience: Ramucirumab with FOLFIRI/XELIRI as a second-line for patients with metastatic gastric cancer

Apatinib in combination with docetaxol and S1 chemotherapy in the first-line treatment of metastatic gastric cancer

L. Xia1, F. Zhou1, J. Dai1, H. Jiang1, L. Yang1, W. Wang1, J. Peng1, J. Gong2 Medical Oncology and Radiation Oncology, Zhongnan Hospital Wuhan University, Wuhan, China, 2GI oncology, Huangshi Central Hospital, Huangshi, China

1

T. Titova1, N. Besova1, E. Artamonova2, E. Perminova3 Chemotherapy, N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation, 2Chemotherapy, FSBI-N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation, 3Chemotherapy, 62 City Oncology Hospital, Moscow, Russian Federation

1

Background: Previous studies demonstrated that the combination of chemotherapy with ramucirumab allows to improve the treatment results in advanced gastric cancer (GC). The one of the available options for the second line chemotherapy is combination of irinotecan with fluoropyrimidines. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of irinotecan and fluoropyrimidines with ramucirumab in metastatic GC. Methods: Eligible patients had advancedmorphologicallyverifiedGC and disease progression during or within 4 months following first-line therapy. They received FOLFIRI plus ramucirumab(8 mg/kg on day 1) or XELIRI in combination with ramucirumab(8 mg/kg on days 1 and 8). The primary end point was progression-free survival (PFS). Secondary end-points were overall survival (OS), disease control rate (DCR) and safety. Results: Between September 2015 and October 2018, 23 patients were enrolled. Median number of cycles was 9 (2-20). Six patients achieved a partial response (PR) for an objective response rate of 26.1%. A total of 15 (65.2%) patients had stable disease (SD) for a DCR of 91.3%. With a median follow up 8,2 months, median PFS was 7.6 months (95% CI 5.9-9.2) and the median OS was 9.5 months (95% Cl 6.74 – 12.3). Median duration of PR response was 4,5 months (2,7-5,2 þ) and median duration of SD was 4,2 months (2,1-10,1þ ).The main treatment-related grade 3 or 4 adverse events were decreased neutrophil count (1/23; 4.3%), anemia (1/23; 4.3%) and diarrhea (1/23; 4.3).The most frequent adverse events of special interest (AESIs) any grade were hypertension (10/23; 43.4%), bleeding/hemorrhage (5/23; 21.7%), proteinuria (5/23; 21.7%) and venous thromboembolic events (6/23; 26%). Gastrointestinal perforationdeveloped in two patients (2/23; 8.7%). No treatment-related deaths occurred. Conclusions: In our research ramucirumab with irinotecan and fluoropyrimidinesdemonstrate the high activity and a manageable safety profile in patients with pre-treated metastatic GC. Legal entity responsible for the study: Besova N.S. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

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

N. Li Oncology, PUMCH-Peking Union Medical College Hospital (West), Beijing, China Background: Alpha-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. Methods: Three 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. Results: We 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

Volume 30 | Supplement 5 | October 2019

Background: Anti-VEGF target therapy is proven to be effective both in second and third line treatment in metastatic gastric cancer. As for Apatinib, which is the tyrosine kinase inhibitor showed highly affinity for VEGFR2, could not only reverse paclitaxel resistance but also improve the R0 resection rate in previous unresected gastric cancer in conversional settings. However, the safety and efficacy of Apatinib in combination with docetaxel plus S1 in the first line treatment of metastatic gastric cancer is unknown and worthy of investigation. Methods: The study was expected to enroll 48 patients diagnosed with metastatic gastric cancer. Each participant was supposed to finish six cycles of chemotherapy plus apatinib (docetaxel 75mg/m2, d1, Q3W; S1 according to BSA: <1.25 40mg po bid; 1.251.5 50mg po bid; >1.5 60mg po bid; d1-14, Q3W; apatinib 500mg po qd). The toxicity was determined according to CTCAE 4.0. Efficacy assessed every two cycles (6 weeks) during the study and every 2 months after finish the study. The primary endpoint was progression free survival (PFS). The secondary endpoint was OS, the objective response rate (ORR), the disease control rate (DCR). The tumor response was determined according to RECIST 1.1 criteria. Results: From July 2017 to April 2019, 32 patients were enrolled. 11 female and 21 male, median age 54 years old, median matastasis organs are 3.5. 80% patients reported adverse events (AEs), most of them are 1-2 AEs. The incidence of grade 3-4 AEs was 35.7%, mainly oral mucositis (23.3%) and myelosuppression (21.5%). For ITT polulation, 24 patients were evaluable for response, 13 patients achieved PR, 4 patients achieved SD, 7 patients experienced PD. The ORR is 54.2%, the DCR is 70.8%. 8 out of 11 per protocol patients have reached primary endpoint, the median PFS is near 6.5 month. Conclusions: Combination therapy with docetaxel and S1 plus apatinib as the first line treatment could be well tolerant, the spectrum of toxicity were not exceeding expectation. This modality also exhibits promising efficacy,which might provide a new therapeutic strategy for metastatic gastric cancer. 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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Parameters of local cellular immunity in metastatic gastric cancer

A.B. Sagakyants1, O.I. Kit2, N.S. Samoylenko1, I.A. Novikova2, E.Y. Zlatnik1, E.M. Frantsiyants3, E.S. Bondarenko1, L.Y. Vladimirova4 1 Laboratory of Immunophenotyping of Tumours, Rostov Research Institute of Oncology, Rostov-on-Don, Russian Federation, 2Administration, Rostov Research Institute of Oncology, Rostov-on-Don, Russian Federation, 3Laboratory of Study of Malignant Tumour Pathogenesis, Rostov Research Institute of Oncology, Rostov-onDon, Russian Federation, 4Medical Department, Rostov Research Institute of Oncology, Rostov-on-Don, Russian Federation Background: A special role in the tumour progression is played by heterogeneous components of the microenvironment of tumours, premetastatic tumour niches, influencing which seems likely to change the disease course. Our purpose was to analyze some characteristics of the local cellular immunity in metastatic GC. Methods: 33 GC patients aged 30-80 years were divided into 2 groups: group 1 – M0, non-metastatic GC, n ¼ 17, mean age 61.768.9 years (G2 – 11, G3 – 6 patients); group 2 – M1, GC with peritoneal and omentum metastases, n ¼ 16, mean age 58.7611.5 years (G2 – 7, G3 – 5, G4 - 3 patients). Tumours (T), peritumoral tissues (PT), omentum (O) and peritoneum (P) tissues were studied. Lymphocytes were determined by flow cytometry using FACSCantoII (BD) and T-, B-, NK antibody panels; quantitative content of DN (CD3þCD4-CD8-), DP (CD3þCD4þCD8þ) T lymphocytes and regulatory (T-regs) T cells (CD4þCD25þCD127dim) was studied.

doi:10.1093/annonc/mdz247 | v309

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Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self): Astellas; Honoraria (self), Advisory / Consultancy: Servier. K. Shitara: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self): Yakult; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Chugai Pharma; Honoraria (self), Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution): Medi Science. E. Van Cutsem: Research grant / Funding (self): Amgen; Research grant / Funding (self): Bayer; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Celgene; Research grant / Funding (self): Ipsen; Research grant / Funding (self): Lilly; Research grant / Funding (self): Merck; Research grant / Funding (self): Merck KgA; Research grant / Funding (self): Novartis; Research grant / Funding (self): Roche; Research grant / Funding (self): Sanofi; Research grant / Funding (self): Servier. N. Causse-Amellal: Full / Part-time employment: Laboratoire Servier. C. LEGER: Full / Part-time employment: Laboratoire Servier. D. Skanji: Full / Part-time employment: Laboratoire Servier. All other authors have declared no conflicts of interest.