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PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

4039 Background: Despite potentially curative surgery, long-term survival from OGC remains poor due to high relapse rate. Neoadjuvant (naFLOT) and adjuvant (aFLOT) FLOT is currently standard treatment for resectable OGC based on data from the FLOT-4 trial. We explored whether TRG was associated with FLOT-outcome using RWD. Methods: Pts with OGC treated with naFLOT +/- aFLOT at a tertiary UK centre were identified following institutional board approval. Clinical and laboratory data were extracted from the patient record. TRG was evaluated by a histopathologist. Median overall survival (OS) and median progression-free survival (PFS) were evaluated using Kaplan-Meier and Log-rank tests; time taken from start of naFLOT, and associations between factors with Fisher’s exact (FE) test. Results: 171 pts were identified, median FU 30 mths. 144 (84%) male; median age 66 (32-84); oesophagus 66 (38%), junctional (GOJ) 73 (43%), gastric 32 (19%); stage IB 3 (2%), stage IIB 26 (15%), stage III 91 (53%), stage IVA 47 (28%) and unknown 4 (2%). Pts had median of 2 comorbidities (range 0-6); performance status (PS) 0: 95 (56%), PS 1: 71 (41%), PS 2: 3 (2%) and PS unknown 2 (1%). 132/171 pts completed 4 cycles of naFLOT and this was significantly associated with undergoing surgery (p = 0.02). Those who had surgery (140/171) had significantly improved PFS (not reached (NR) vs. 6 mths; 95% CI 2-10; p < 0.001) and OS (NR vs. 12 mths; 95% CI 6-18; p < 0.001). TRG was reported for 126/140 patients who underwent surgery. TRG 1/2 (42/126) vs. TRG ≥3 was significantly associated with improved PFS (NR vs. 35 mths; 95% CI NR; p < 0.001) and OS (median NR either group; p < 0.001). Pts with TRG 1/2 who commenced aFLOT (≥1 cycle; n = 31/42) or completed 4 cycles of aFLOT (17/31) did not have improved PFS or OS vs. those who did not. Those with TRG ≥3 who commenced aFLOT (≥1 cycle; n = 62/85) had improved PFS (median NR vs. 22 mths; 95% CI 13-31 p = 0.006) and OS (median NR vs. 25 mths; 95% CI 18-32 p = 0.019). Those with TRG ≥3 who completed 4 cycles of aFLOT (n = 38/62) had significantly improved PFS (median NR vs. 25 mths; 95% CI 14-36 p = 0.016) and OS (median NR vs. 36 mths; 95% CI 16-55 p = 0.012). There was no difference in PFS or OS in pts with TRG ≥3 who had a dose reduction at any time during aFLOT. Conclusions: TRG is a predictor of outcome following naFLOT + surgery with superior outcomes in those with TRG 1/2. Our analyses suggest that only pts with TRG >3 following naFLOT + surgery benefit from adjuvant FLOT. Prospective randomised studies are required to confirm whether pts with TRG 1/2 require treatment with aFLOT.

349 Background: In a real-world scenario, Fluorouracil-based triplet combination chemotherapies have limited feasibility with regards to toxicity, need for central venous access, and hospitalization. The primary objective of this study was to assess pathological tumor regression to Capecitabine-based triplet regimes, with the additional possible benefit of overcoming the aforementioned barriers. Methods: This Single-Arm, Prospective study investigated the primary outcome of histopathologic regression to perioperative Docetaxel, Oxaliplatin, and Capecitabine (DOX) combination regime in histologically confirmed resectable Esophageal, Esophagogastric Junction, and Gastric Adenocarcinomas. Three preoperative and 3 postoperative cycles of Docetaxel 60mg/m2 plus Oxaliplatin 100mg/m2 on Day 1, with Capecitabine 500mg/m2 twice daily from Day 1 to Day 21 were administered, with cycles repeating every 21 days. Histopathologic regression was assessed by Modified Ryan’s Schema on surgical specimen. The study had an 80% power (two-sided significance of 0.05) to detect a 20% pathological complete response. Secondary endpoints were Overall Survival, Progression-Free Survival, and Toxicity analysis. Results: Between June 2017 to May 2019, 28 patients (median age 54.5 years [Range 33 – 82]; Male 78.6%; ECOG PS 1/2 = 42.9%/57.1%) were enrolled in the study of which 92.9% completed preoperative chemotherapy. Of the 20 patients operated upon, 100% were R0 resections. Pathological complete response was observed in 20% (4/20). Ninety percent of the operated patients completed the postoperative treatment. The most common grade ≥3 toxicities were Palmar-Plantar Erythrodysesthesia (10.7%), Fatigue (10.7%), and Diarrhoea (7.1%). Conclusions: Perioperative DOX met its primary endpoint of 20% pathologic complete regression with a favourable toxicity profile and was feasible to administer in resectable Esophageal, Esophagogastric Junction, and Gastric Adenocarcinomas. This regimen deserves further evaluation in larger phase III trials.

178 Background: Triplet chemotherapies, with fluoropyrimidines, platin derivates and Docetaxel, represent an option for first line treatment of metastatic Gastro-Esophageal Adenocarcinoma (mGEA). To increase tolerability and dose intensity (DI), we previously developed an alternative way of administration of 5Fluorouracil (5FU), with nocturnal “timed-flat infusion” (TFI) (from 10:00 PM to 10:00 AM), without 5FU bolus and Folinic Acid, in several combination-schedules in breast and colorectal cancers. Methods: We report a retrospective analysis of 27 mGEA patients (pts) treated with FD/FOx regimen, a schedule of weekly TFI/5FU for two nights at 1000 or 900 mg/m2/night, associated to alternating Docetaxel at 50 mg/m2 on days 1 and 15, and Oxaliplatin at 80 mg/m2 on days 8 and 22, cycles repeated every 4 weeks. Results: From June 2007 to July 2017, 17 pts (62.9%) were treated with standard FD/FOx and 10 pts (37.1%) with modified FD/FOx (defined by any projected dose reduction compared to standard) due to age, PS and comorbidities. Median age was 60 years (range 41-80), male/female ratio 19/8, ECOG-PS 0, 7 (26%), 1, 16 (59%), 2, 4 (15%); 17 pts (62.9%) had a Cumulative Illness Rating Scale Intermediate stage, 1 patient (3.7%) a Secondary one. Thirteen pts (48%) had unresected primary tumor. ORR, median PFS and median OS were 73.9% (α0.05, CI±18), 13 and 16 months, respectively. The only G4 toxicity was neutropenia (11.1%); G3 were: neutropenia (29.6%), asthenia (22.2%), diarrhea (22.2%); most relevant G2 toxicities were: nausea (33.3%), anorexia (40.7%), neuropathy (37.0%) and anemia (40.7%). No febrile neutropenia was observed. The received (r)DI were 80% of standard full dose of each drug: Docetaxel 20 mg/m2/week, Oxaliplatin 32 mg/m2/week and 5FU 1440 mg/m2/week. Out of 21 pts who progressed to FD/FOx, 13 pts (48.1%) underwent a second line therapy (6 rechallenges with taxanes). Conclusions: Even if requires a careful management, FD/FOx is a feasible option for first line treatment of mGEA pts, particularly in needing of tumor shrinkage, with significant activity, high rDIs, and acceptable safety profile when compared to literature.

174 Background: Although the triplet regimen of docetaxel/cisplatin/S-1 (DCS) has shown promising activity and conversion rate in patients with unresectable metastatic gastric cancer (UMGC) in Japan, it was accompanied by severe adverse events. Recent studies suggested that oxaliplatin was almost as active, and relatively less toxic, than cisplatin in combination regimens for UMGC and can therefore replace cisplatin. The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), recommended dose (RD), and preliminary efficacy of docetaxel/oxaliplatin/S-1 (DOS) instead of DCS in patients with UMGC. Methods: Previously untreated 16 patients with histologically proven UMGC were enrolled. Docetaxel and oxaliplatin were administered intravenously on day 8. S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 3 weeks. DLTs were evaluated during the first cycle of treatment. Three dose-escalations of DOS were used in this study namely, level 1 (50/100/80 mg/m2), level 2 (50/130/80 mg/m2), and level 3 (60/130/80 mg/m2). Results: Among the six patients, one patient each experienced DLTs (febrile neutropenia and diarrhea) at level 1 and 2 doses, respectively. While two more patients experienced DLTs (febrile neutropenia and diarrhea) after administration of level 3 doses. Therefore, two additional patients were enrolled into the study at level 2. However, both these patients subsequently exhibited DLTs (febrile neutropenia and diarrhea). Therefore, we concluded that the MTD and RD with this regimen were level 2 and level 1, respectively, and that the DLT were grade 3 diarrhea and febrile neutropenia. The overall response rate was 78% (7/9) of the patients with measurable lesions, consisting of two complete response and five partial responses. Five patients underwent conversion surgery. Conclusions: The RD of the 3-weekly DOS regimen in patients with UMGC was docetaxel at 50 mg/m2 and oxaliplatin at 100 mg/m2 on day 8 and S-1 at 80 mg/m2 on days 1-14. The efficacy and ease of administration make the regimen a promising alternative to DCS. A phase II study using this RD regimen is currently underway. Clinical trial information: 000015849.

e15065 Background: So far, the prognosis of advanced gastric cancer is dismal. Combination chemotherapy of docetaxel (D), cisplatin (C) and fluorouracil (F) showed activity in metastatic gastric cancer, but this regimen was complicated by a high incidence of myelotoxicity. We performed a multicenter phase II trial substituting C with oxaliplatin (O) and F with capecitabine (X) in chemotherapy-naive patients (pts) with gastric or GEJ adenocarcinoma. Methods: Pts with measurable distant metastases received D 60 mg/mq iv, O 100 mg/mq iv on day 1 and X 500 mg/mq orally twice daily continuously, with cycles repeated every 3 weeks for a maximum of 8. G-CSF was used only as secondary prophylaxis. The primary endpoint was overall response rate (RR) according to RECIST. Toxicity was reported according to NCI-CTC v 3.0. Optimal Simon's two-stage design was employed with 6/15 responses required in the first stage to allow continuation to 46 pts. Results: 46 pts were enrolled: M/F 28/18; median age 66 years (32-75); median ECOG PS 1 (0-2); primary tumor resected/ unresected 16/30; disease location was gastric in 34 and GEJ in 12 pts; sites of disease were liver in 27, nodes in 25, peritoneum in 20, lung in 8 and bone in 5 pts. At the time of analysis all pts were evaluable for response and toxicity. In 46 pts, 3 CR and 21 PR were observed, for an overall RR of 52.1% (95% CI, 37.7%-66.5%). Responses were obtained in 15/27 pts (55%) with liver metastases. Disease remained stable in 14 pts (30.5 %). Median TTP was 6.8 months and median OS was 12.6 months. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 41%, 4% and 9% of the pts, respectively. Febrile neutropenia was observed in 2 pts (4%). Other grade 3 toxicities included mucositis in 2 pts (4%), vomiting in 3 pts (6.5%) and diarrhea in 2 pt (4%). There were no severe neurotoxicity, nor treatment-related deaths. Conclusions: The DOX combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomized trials and, hopefully, in neoadjuvant setting.

4099 Background: Three drug regimen of docetaxel with cisplatin and 5-FU is an established first line treatment for metastatic or locally advanced GC, improving overall survival and response rates,...

e15541^ Background: We previously reported results of a phase I study of oxaliplatin, docetaxel, and capecitabine for advanced esophagogastric cancer (Evans et al, Am J C Onc 2007). In this phase II component we describe response rates, toxicity, and survival data. Methods: Patients with histologically confirmed metastatic esophagogastric squamous or adenocarcinoma were eligible. Patients received oxaliplatin 50mg/m2 and docetaxel 35mg/m2 on days 1 and 8 as well as capecitabine 750 mg/m2 twice daily on days 1–10 in each 21 day cycle. Results: 21 patients were enrolled and were evaluable. Median age was 65, range 46–83. All had adenocarcinoma histology. Three patients received prior adjuvant or neoadjuvant therapy. A total of 91 cycles were delivered, median of 4, range of 1–11. Median follow-up was 2 years; all patients have been followed for at least 1 year. Median overall survival was 11 months. The overall response rate was 43%. Three patients achieved a complete response. Two of these patients remain without evidence of disease at 38 and 12 months. Three patients experienced confirmed pulmonary emboli, and one patient expired at home with possible pulmonary embolism (exact cause unknown).Other Grade 3/4 toxicities were: nausea (3/21), fatigue (2/21), diarrhea (4/21), hand/foot (1/21), dehydration (3/21), esophagitis (2/21), infection (1/21), Electrolyte (3/21), neutropenic fever (2/21), neutropenia (4/21), anemia (1/21). Conclusions: DOC is an active and easily administered regimen for metastatic esophagogastric cancer. Consideration should be given for prophylactic anticoagulation for patients with metastatic esophagogastric cancer. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

e19010 Background: No combination regimen has proven superior to single agent chemotherapy as 2nd-line treatment for NSCLC. The absence of cross-resistance with cisplatin/carboplatin, favorable toxicity profile, along with both pre-clinical and clinical evidence of activity make O a good candidate for combination with D as 2nd-line therapy of NSCLC. We evaluated the activity of DO in this setting using a novel phase II trial design. Methods: This multicenter, non-comparative randomized phase II trial evaluated the activity of D (75 mg/m2 d1) and O (70 mg/m2 d2) every 3 weeks in previously treated NSCLC pts; the comparator arm was D (75 mg/m2 d1 every 3 weeks). This one-stage, three-outcome phase II trial design (Sargent, Control Clin Trials 2001) had 21 evaluable pts/arm. All had histologically confirmed NSCLC that progressed during/after platinum-based chemotherapy. Primary endpoint was response rate; secondary endpoints were toxicity, time to progression (TTP), 1-yr survival. Results: Fifty pts were enrolled. Pts characteristics: M/F, 76/24%; median age 62 yrs (range 43–69); ECOG PS 0/1, 36/64%; adenocarcinoma/other, 36/64%. With 48 pts evaluable, partial response was seen in 20% and 8% of pts; stable disease in 52% and 32% and progressive disease in 24% and 56% for DO and D, respectively; 1 pt was inevaluable due to early death (D arm). Main grade 3–4 toxicities were: neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhea 12% and 4% for DO and D, respectively. Median TTP was 4.9 and 1.8 months, median survival 10.9 and 6.9 months, and 1-yr survival 41% and 16% for DO and D, respectively. Conclusions: This study shows how novel phase II trial designs enrolling a limited number of pts may help identify promising regimens for subsequent study in phase III trials. The level of activity for DO we observed satisfied the pre-defined study primary endpoint and warrants further evaluation of this combination as 2nd-line therapy for NSCLC. Protocol developed at the 6th FECS/AACR/ASCO Workshop on Methods in Clinical Cancer Research, Flims 2004, with Professors Marc Buyse and Chris Twelves. [Table: see text]

14051 Background: Combination regimens of 3 active drugs have shown promising activity in treatment of metastatic gastric cancer (GC). Docetaxel (D) combined with cisplatin and 5-FU (CF) yielded superior overall survival and response rates when compared to standard CF. However, toxicity profile showed the need for development of less toxic modifications. In this phase I trial, D was combined with oxaliplatin (Ox) and capecitabine (Cape) in order to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients (pts) with metastatic GC. Methods: Pts had to have metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, no prior chemotherapy. Four dose levels were planned planned for the TEX regimen: D 35–40 mg/m2, Ox 70 mg/m2 d1 and d88, with Cape 800–1000 mg/m2 bid d1–14 q d22. Toxicity was assessed 3-weekly whereas CT scans were repeated 9-weekly. Results: 14 pts were enrolled: 9m/5f, age 64 (42–76) yrs, ECOG PS 1 [0–2]. All pts. had distant metastatis, 10 no gastrectomy. On dose level 1 (D 35 mg/m2, Ox 70 mg/m2, Cape 800 mg/m2) 3 pts were included initially. 1 pt. had grade 4 bleeding from primary tumor site after 2nd administration and therefore was excluded. For safety reasons, 6 more pts. were enrolled - without further DLT. On dose level 2 (D 40 mg/m2, Ox 70 mg/m2, Cape 800 mg/m2), diarrhea and mucositis grade 3 occurred as DLT in 2/2 patients. Level 1 was determined as MTD and 5 more pts were included to a total of 12 with toxicity displayed at the table. Out of 10 pts with measurable disease, 3 had a PR, 4 more had disease stabilization. Median PFS of all pts (5 censored) is 3.9+ (1–9.3+) mos. whereas median OS is not yet reached. Conclusion: TEX can safely be administered without higher graded toxicity in pts with GC. Preliminary efficacy results indicate promising activity that merits further testing in a phase II trial. [Table: see text] [Table: see text]

14076 Background: Chemotherapy remains the main treatment option for metastatic oesopagogastric cancer (MOC) patients (Pts). First-line regimens have proved a slight but significant increase in quality of life and survival, but a standard regimen has not been defined yet. Several new drugs, as Docetaxel (D), Oxaliplatin (O) and Capecitabine (C) have demostrated activity in MOC. They have shown synergy in preclinical models and activity in previous phase II trials. The purpose of our study is to asses activity and feasibility of the combination of D, O and C as first-line chemotherapy in MOC patients. Methods: MOC patients, with good ECOG performance status and chemonaive are eligible. Pts receive D 60 mg/m2 day 1, O 85 mg/m2 day 1 and oral C 650mg/m2 bid d1–14 every 3 weeks. Primary endpoints are response according to WHO criteria and toxiciy assesment according to NCI.CTCAE v3.0. Results: From November 2004 to December 2005, 17 Pts have been enrolled. Median ECOG PS is 1 (0–2) M/F:9/8. Median age is 57 years (38–68) Primary tumor are gastric carcinomas (82%) and lower oesofagus carcinomas (18%). Metastatic sites included peritoneum 58%, liver 23% and lung 23%. Median number of cycles is 5 (1–7) Treatment is well tolerated with no toxic deaths. NCI grade 3–4 toxicities include 2 Pts (11.8%) with grade 4 neutropenia and one of them developed septic shock; 2 Pts with grade 3 asthenia, 1 Pt with grade 3 vomiting and 1 patient with grade 3 neurotoxicity. Main NCI grade 2 toxicities are dhiarrea (35.3%) and neurotoxicity (23.5%). 13 Pts have been evaluated for response until now: 9 Pts have a confirmed Partial Response (69.2%) and 2 of them underwent salvage surgery; 3 Pts have Stabilized Disease and 1 Pt Progression Disease. Median time to progression and median overall survival have not been reached yet and the study is still ongoing. Conclusions: The combination of D, O and C at the dosses and schedule used in this trial is effective in MOC with a manageable toxicity profile No significant financial relationships to disclose.