Cycles Of FLOT Research Articles

Effect of chemotherapy/targeted therapy alone vs. chemotherapy/targeted therapy followed by radical surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction: The IKF-575/RENAISSANCE phase III trial.

LBA4001 Background: The IKF-575 trial investigates the long-standing question about the role of surgical intervention in limited-metastatic gastric / esophagogastric junction cancer after systemic induction therapy. Methods: Previously untreated patients (pts) with limited metastatic disease (retroperitoneal lymph node (RPLN) metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) received 4 cycles of FLOT, + trastuzumab if Her2+ or + nivolumab if PD-L1 positive. Pts without progression after 4 cycles were randomized to receive additional FLOT (Arm B) or radical complete surgical resection of primary and metastases followed by the same treatment (Arm A). It was planned to randomize 176 pts for which 271 pts had to enrolled. The primary endpoint was overall survival in the ITT population using Kaplan-Meier estimates. Recruitment was stopped after enrollment of 183 patients (141 patients randomized) with minimal impact on statistical power, due to a slow enrollment rate. Results: The ITT comprised 139 pts (A, 67; B, 72): 20% had RPLN metastases only, 58% organ metastases only, and 22% had both. Surgery in Arm A (ITT) was performed in 91% of pts and R0-resection rate (primary) was 82%. 30-d and 90-d mortalities in the surgery population were 3% and 8%. At least 4 additional cycles of post-op or post-randomization chemotherapy were achieved in 42% of pts in Arm A vs. 71% of pts in Arm B. The primary endpoint ovrall survival was not met due to increased early mortality in the surgery Arm leading to crossing survival curves with OS 25%- and 75%-Quantiles being 10 vs. 14 months and 65 vs. 41 months for Arms A vs. B, respectively. Pts with RPLN metastases only seemed to benefit most from the surgical approach (mOS, 30 vs. 17 months; 5y OS 38% vs. 19%; still having increased early mortality), while pts showing no response to chemo (mOS, 13 vs. 22 months) or pts with peritoneal disease (mOS, 12 vs. 19 months) derived a detrimental effect. Conclusions: The IKF-575/RENAISSANCE trial is negative but informs future research. Future protocols should focus on pts with RPLN only disease and exclude non-responding pts or those with peritoneal disease. There is a need for strategies against the early mortality caused by chemotherapy interruption. Clinical trial information: NCT02578368 .

Long-term survival comparison of adjuvant FLOT versus XELOX chemotherapy for locally advanced gastric cancer in a large real-world cohort.

4080 Background: Recent Attraction-5 study has shown that logically advanced gastric cancer (LAGC) patients can't benefit from postoperative immunochemotherapy. The preferred adjuvant regimen for LAGC remains two-drug based chemotherapy as XELOX protocol, though three-drug based adjuvant FLOT regimen has not been well studied yet. This studyaimsto explore 10-year survival advantages of adjuvant FLOT versus XELOX regimen for LAGC. Methods: We retrospectively collected and analyzed data from 248 LAGC patients mainly composed of pathological T (pT) 3-4 stage, who received at least 4 cycles of FLOT or XELOX adjuvant chemotherapy at Lanzhou University Second Hospital from 2013 to 2018. To eliminate interference of confounding factors, we conducted a propensity score matching (PSM). The median follow-up time for all patients was 90.90 months. Results: After PSM, the median overall survival (OS) was 44.80 months in FLOT group and 34.87 months in XELOX group, with 5-year OS rate of 41.4% versus 25.3% and 10-year OS rate of 31.9% versus 11.8%. Subgroup analysis showed that patients with ECOG performance status 0 or pT3-4 stage attained significant survival benefits from adjuvant FLOT regimen. Grade 3-4 treatment-related adverse events occurred in 57.9% patients of FLOT group and 33.6% patients of XELOX group, while most of them were manageable. Conclusions: This study demonstrates that adjuvant FLOT regimen exhibits significantly long-term survival advantages for LAGC patients with good performance status and late disease stage compared with XELOX regimen, facilitating adjuvant FLOT regimen as a prospectively alternative option for LAGC.

Aggressive HER2-Positive Gastric Cancer in a Young Patient, Refractory in Trastuzumab and Progressive with Trastuzumab-Emtansine Treatment

Gastric cancer remains a major global health problem. Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related deaths in the world. The prognosis of the disease is poor because it is often diagnosed at later stages, especially at HER2-positive. Most patients diagnosed with gastric cancer present with advanced, incurable disease. This report details the case of a 30-year-old male patient diagnosed with metastatic gastric adenocarcinoma. Stage T3 N3 M1, PD-L1 0%, and HER2+.The patient was administered neoadjuvant palliative chemotherapy, eight cycles of FLOT, and the last two cycles of HER-FLOT. The patient constantly had elevated levels of liver enzymes, and therefore, endoscopic retrograde cholangiopancreatography with biliary stenting was performed. After chemotherapy followed by restaging, the tumor board, based on the findings, decided to remove the primary tumor from this young patient. The operation was performed as a palliative da Vinci-assisted total gastrectomy with lymphadenectomy. Then, trastuzumab monotherapy was prescribed. At that time, the patient's follow-up with PET-CT showed progression with hypermetabolic lymph nodes in the paraaortic and aortocaval regions, as well as left hydronephrosis. As a result, we started the second-line therapy with T-DM1, an antibody-drug conjugate trastuzumab-emtansine (KADCYLA), for five cycles. At the time of receiving the sixth cycle, the patient's condition changed dramatically due to liver and heart problems, pleural effusion, and bleeding. After two years of treatment, all oncological-specific therapies have been ended, and the patient has been put in palliative care to relieve suffering and to support the best possible quality of life. This case underlines the importance of identifying potential therapeutic targets and developing therapies to improve the outcomes of systemic treatment beyond those currently achieved with conventional chemotherapy and targets.

FLOT plus nivolumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: Results from the randomized phase 2 IKF-S628/AIO-STO-0417 (Moonlight) trial of the AIO.

4045 Background: FOLFOX plus nivolumab (nivo) has become standard of care for first-line therapy of patients (pts) with esophagogastric adenocarcinomas. FLOT is a well-established standard of care triplet regime. Some physicians may consider a triplet in patients with aggressive disease. The aim of this Arm C part of the Moonlight trial was to evaluate the safety and efficacy of the combination of FLOT plus nivo. Methods: Moonlight is a multi-cohort phase-II trial. The results for Arm C evaluating FLOT + nivo (240 mg) q2w as first-line therapy in all-comers are presented here. Primary endpoint was progression-free survival at 6 months (PFS@6), main secondary endpoints were safety, OS, and overall response rate (ORR). Results: Fifty-two patients were enrolled. Baseline characteristics were: median age 61y, GEJ 65%. Sixty-five percent had centrally assessed PD-L1 CPS≥1 (available in 96% of pts). Pts. received a median number of 8 cycles of FLOT and nivo and 42% received further line treatment. FLOT plus nivo was well tolerated and feasible with the most frequent adverse events of ≥ grade 3 being decreased neutrophils (40.4%), anemia (5.8%) and thromboembolic events (7.7%). After a median follow-up of 9.4 months, 3- and 6-month progression-free survival rates were 85% and 42%, respectively. Median PFS was 6.6 months and median OS 10.8 months. ORR and disease control rate (DCR) were 54% and 87%, respectively. Compared to the pooled study cohorts A and A1 (n = 90 pts) utilizing mFOLFOX plus nivo and ipilimumab (non-randomized comparison), FLOT plus nivo was associated with greater DCR (87% vs. 78%) and 3-months PFS (85% vs. 72%). Conclusions: FLOT and nivo is feasible and seems to be associated with improved disease control in the early course of therapy. FLOT plus nivo may represent an option for select patients with aggressive, rapidly progressive disease. Clinical trial information: NCT03647969 .

P-OGC24 Comparison of the histopathological regression after neoadjuvant FLOT versus ECX in resectable gastroesophageal adenocarcinoma

Abstract Background Neoadjuvant chemotherapy is a key component in the treatment of resectable oesophagogastric cancer (OGC). Histopathological tumour regression is associated with a prognostic benefit in OGC. There is increased usage of the FLOT regimen as part of neoadjuvant chemotherapy (NAC) for these tumours. The initial phase 2 trial demonstrated complete pathological response (pCR) in 15% for FLOT versus 6% for ECX but there is no data outside a trial setting. The aim of this study was to evaluate the differences in pCR and the extent of downstaging between patients receiving FLOT versus ECX in the neoadjuvant setting. Methods Consecutive patients treated for OGC in a single, high-volume UK centre between 2018 and 2021 were identified from a contemporaneously maintained database. Patients underwent 3 cycles of ECX or 4 cycles of FLOT as part of NAC. Histopathological tumour regression was assessed by the Mandard classification. A comparison of T- and N stage migration between FLOT and ECX was performed. Major pCR was defined as TRG 1-2 based on the Mandard classification. Results The study included 162 patients. 6/84 (7.1%) patients receiving ECX and 5/78 (6.4%) patients receiving FLOT achieved a pCR (p = 0.853). 11/84 (13.1%) patients in the ECX group and 12/78 (15.4%) patients in the FLOT group achieved a major pCR (p = 0.677). With regards to stage migration by T-stage, 36 (42.9%) patients were downstaged and 6 patients (7.1%) were upstaged with ECX. Amongst FLOT patients, 42 (53.8%) were downstaged and 8 (10.3%) upstaged (p = 0.189). When comparing N-stage, 29 (34.5%) patients achieved downstaging and 28 (33.3%) were upstaged with ECX. 30 (38.5%) patients were downstaged and 20 (25.6%) were upstaged with FLOT (0.563). Conclusions There was no significant difference in pCR and stage migration rates between patients receiving neoadjuvant ECX and FLOT. pCR rates were lower than previously reported, and it is unclear if the difference in prognosis will translate comparable outcomes between patients receiving ECX versus FLOT.

RACE-trial: neoadjuvant radiochemotherapy versus chemotherapy for patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction - a randomized phase III joint study of the AIO, ARO and DGAV

BackgroundDespite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted.MethodsThe RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life.DiscussionThe RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone.Trial registrationClinicalTrials.gov; NCT04375605; Registered 4th May 2020;

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

FLOT perioperative chemotherapy is the standard treatment in patients with resectable gastric and gastroesophageal junction (GEJ) cancer. There is a lack of information if tumor location or inflammatory biomarkers are associated with tumor regression after chemotherapy treatment. The aim of this study is to determine associated factors with tumor regression after FLOT therapy. This is a retrospective observational study of a single patient cohort. Clinical records of patients with clinical stage II and III gastric and GEJ cancer were recollected, since January 2018 to December 2019, in ALIADA cancer center and Rebagliati Hospital, in Peru. Clinical stage was determinate using AJCC 8th edition and was evaluated before therapy and after surgery to determine tumor regression. Tumor location was evaluated in endoscopy reports; meanwhile NLR and PLR were calculated from blood counts before the beginning of chemotherapy. Clinical records with incomplete data were excluded. The bivariate statistical analysis was performed with Chi-squared test, Odds ratio and logistical regression was performed with a confident level of 95% (p< 0.05). 52 clinical records were evaluated and finally 41 were included. 63% were male and the mean age was 58 years. All patients had adenocarcinoma type histology, 65% of them had diffuse subtype and the rest intestinal subtype. The 63% of patients had gastric cancer distributed as follows: 50% in corpus, 35% in antrum, 10% in cardia and 5% fundus. 37% of patients had GEJ cancer; the 53% of them were siewert II and 47% siewert III. The 90% of patients had clinical stage III and 10% clinical stage II. All patients received four cycles of FLOT and the 82% were operated. 78% of patients had tumor regression after chemotherapy; 12% of them achieved pathological complete response. The 17% of patients had stable disease and 24% had progression of disease, 71% of them progressed to peritoneum. Diarrhea (27%) and emesis (20%) were the most frequent adverse events presented in our population meanwhile neutropenia (8%) and anemia (5%) were the most frequent grade III-IV adverse events. There was no statistic difference between patients who had tumor regression compared to patients who did not have response to chemotherapy with respect to mean NLR (2.61 ± 0.27 vs 2.84 ± 0.31, p>0.05) and mean PLR (2.61 ± 0.27 vs 2.84 ± 0.31, p>0.05). Tumor regression was more frequent in patients with gastric cancer (69% vs 63%, p=0.02). There was no statistic difference in the multivariate analysis (OR = 148, IC95% = 0.34-6.40). Tumor regression was associated with tumor location in bivariate analysis, being more frequent in patients with gastric cancer; however there was no statistic difference in multivariate analysis. Studies with bigger amount of patients are needed to validate this association.

Operative Results and Perioperative Morbidity After Intensified Neoadjuvant Chemotherapy with FLOT for Gastroesophageal Adenocarcinoma Impact of Intensified Neoadjuvant Treatment

BackgroundPerioperative treatment is the standard of care in Western Europe for locally advanced gastric cancer (GC) and adenocarcinoma of the gastroesophageal junction (GEJ). Intensified neoadjuvant treatment within the NeoFLOT trial proved to be safe and effective. Yet, the influence of such intensification with 6 cycles of FLOT in the neoadjuvant setting has not been analyzed regarding its possible impact on perioperative results. Materials and MethodsA total of 537 patients were enrolled in this study; of whom, 132 had followed a standard neoadjuvant protocol (CTx), 356 had not received any neoadjuvant treatment (NoCTx), and 49 patients had undergone an intensified chemotherapy within the NeoFLOT trial (IntCTx) with 6 cycles of FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) every 2 weeks. ResultsOur results reveal no significant difference in perioperative morbidity or mortality with regard to the neoadjuvant treatment. Postoperative bleeding and hematoma occurred less frequently in the IntCTx group compared to the NoCTx and the CTx groups (2.0% vs. 5.33% vs. 5.1%). Postoperative lymph fistulas were slightly more frequent in the IntCTx group (4.1% vs. 0.3% vs. 1.6%). Patients treated within the NeoFLOT trial had a higher risk for blood transfusions (OR 5.5; 95%-KI, 2.49–12.19), whereas patients without neoadjuvant therapy had the longest ICU stay (mean 8.3 vs. CTx 4.5 vs. IntCTx 6.7 days). ConclusionThe results of the current study indicate that also an intensification of neoadjuvant chemotherapy with 6 preoperative cycles of FLOT does not significantly increase perioperative complications. Thus, prolonged neoadjuvant chemotherapy with FLOT is safe for patients with locally advanced GC or GEJ tumors.

Perioperative chemotherapy alone versus preoperative chemoradiotherapy for locally advanced distal esophageal and gastroesophageal junction cancer: A 10-year review of the British Columbia (BC) Cancer Registry.

4028 Background: The optimal treatment strategy for resectable cancer of the distal esophagus (ESOPH) and gastroesophageal junction (GEJ) remains controversial. This study evaluates patterns of practice in BC, rates of complete surgical resection, and survival outcomes of patients treated with perioperative chemotherapy alone (CA), per MAGIC or FLOT4 protocol, versus preoperative chemoradiotherapy (CRT), per CROSS protocol. Methods: We undertook a provincial analysis of initially resectable, locally advanced, cancer of the ESOPH and/or GEJ who underwent surgery in BC, from 2008 to 2018. Baseline patient, tumor, treatment, and clinical outcome data were collected from the BC Cancer Registry. Kaplan-Meier survival and multivariate regression analyses were conducted. Results: Among 575 patients, 468 underwent surgery and were included (Table). More surgeries were aborted intraoperatively in the CA cohort compared to CRT (12% vs 2%, p&lt;0.001). There was no difference in age, sex, or ECOG performance status among the cohorts, and 83% were adenocarcinoma. While 82% of ESOPH involving GEJ (N = 251, 54%) is treated with CRT, only 53% of GEJ alone (N=217, 46%) is treated with CRT (p&lt;0.001). CRT is associated with a higher rate of complete or partial pathologic response compared to CA (59% vs 39%, p=0.002). R0 resection rate was 90% and 94% in the CA and CRT cohort, respectively (p=0.383). There is no statistically significant difference in overall survival, with medians of 29.6 and 26.0 months for patients treated with CA and CRT, respectively (p=0.723). Cancer-specific survival is also not significantly different (p=0.565). In the CA cohort, 37% of patients complete all 8 cycles of FLOT and 52% of patients complete all 6 cycles of MAGIC (p=0.396). Conclusions: Patients treated with CRT have higher rates of complete resection and pathologic response, but their survival is not significantly different compared to those treated with CA. [Table: see text]

PS02.102: RESULTS FROM MULTICENTER, RANDOMIZED PHASE 3 FLOT4-AIO-TRIAL

Abstract Background The MAGIC trial established perioperative (periop) epirubicin, cisplatin, and 5-FU (ECF) as a standard treatment for patients (pts) with operable esophagogastric cancer, but survival continues to remain poor. FLOT4 (NCT01216644) is a multicenter, randomized, investigator-initiated, phase 3 trial (AIO-trial). It compares the docetaxel-based triplet FLOT with the anthracycline-based triplet ECF/ECX as a periop treatment for pts with resectable gastric or GEJ adenocarcinoma. Methods Eligible pts of stage ≥ cT2 and/or cN + were randomized to either 3 preoperative and 3 post-operative 3-week cycles of ECF/ECX (epirubicin 50 mg/m2, cisplatin 60 mg/m², both d1, and 5-FU 200 mg/m² as continuous infusion or capecitabine 1250 mg/m2 orally d1–21) or 4 pre-operative and 4 post-operative 2-week cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m², leucovorin 200 mg/m², and 5-FU 2600 mg/m² as 24-hour infusion, all d1). The primary endpoint was overall survival (OS; 80% power; HR of 0.76; 2-sided log-rank test at 5% type I error). Results Between Aug 2010 and Feb 2015, 716 pts (360 ECF/ECX; 356 FLOT) were randomly allocated. Baseline characteristics were similar between arms (overall, male 74%; median age 62; cT3/T4 81%; cN + 80%; GEJ 56%). 91% and 37% of pts with ECF/ECX and 90% and 50% with FLOT completed planned pre-operative and post-operative cycles, respectively. Median follow-up was 43 mon. 369 pts died (203 ECF/ECX; 166 FLOT). FLOT improved OS (mOS, 35 mon with ECX/ECF vs. 50 mon with FLOT; HR 0.77 [0.63 - 0.94]; P = 0.012). 3y OS rate was 48% with ECF/ECX and 57% with FLOT. FLOT also improved PFS (mPFS, 18 mon with ECX/ECF vs. 30 mon with FLOT; HR 0.75 [0.62 - 0.91]; P = 0.004). Periop complications were 50% with ECF/ECX and 51% with FLOT. 30- and 90-day mortality was 3% and 8% with ECF/ECX and 2% and 5% with FLOT. There was more G3/4 nausea and vomiting with ECF/ECX and more G3/4 neutropenia with FLOT. Conclusion Periop FLOT improved outcome in patients with resectable gastric and GEJ cancer compared to periop ECF/ECX. Disclosure All authors have declared no conflicts of interest.

Intraperitoneal immunotherapy with the bispecific anti-EpCAM x anti-CD3 directed antibody catumaxomab for patients with peritoneal carcinomatosis from gastric cancer: Final results of a randomized phase II AIO trial.

4 Background: The peritoneal surface is a common location for metastases in gastric cancer (GC). Intraperitoneal (i.p.) application of the bispecific (anti-EpCAM/CD3) monoclonal antibody catumaxomab (CATU) in addition to i.v. chemotherapy may improve elimination of peritoneal carcinomatosis (PC). Methods: This randomized open-label phase II study aimed to investigate the efficacy of i.p. CATU following i.v. chemotherapy in patients (pts) with GC and PC (Gilly stages P1-4). Pts were randomly allocated to receive four cycles of FLOT (5FU, LV, Oxaliplatin, Docetaxel) followed by i.p. CATU at escalating doses (10, 20, 50, 150µg) on days 0, 3, 7, 10 or FLOT alone. Secondary gastrectomy and peritonectomy were allowed to achieve complete resection of all malignant lesions. The primary endpoint was to show an increased rate of macroscopic complete remission of PC at second-look surgery. Secondary endpoints included toxicity, progression-free and overall survival (PFS/OS). Results: Of 35 pts screened, 31 were enrolled. Median follow-up time is 52 months. 15 pts were allocated to FLOT-CATU (arm A) and 16 to FLOT alone (arm B). Complete remission rate of PC was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects with i.p. CATU were nausea (15%), fever (23%), abdominal pain (31%), and elevated liver enzymes (gGT 31%, bilirubin 23%). Adverse events tended to be more common during FLOT-CATU compared to FLOT alone. Median PFS was not significantly different in both arms with 6.7 months in arm A compared to 5.4 months in arm B (p = 0.71). Median OS was 13.2 and 13.0 months. Conclusions: Addition of i.p. CATU as part of a multimodal treatment approach revealed feasible and tolerable in pts with GC and PC. Although the primary endpoint was not met, the results are promising for future trials investigating i.p. immunotherapy in this patient population. Clinical trial information: NCT01504256.

The “RENAISSANCE” Trial: Effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction—A phase III trial of the German AIO/CAO-V/CAOGI.

TPS4140 Background: Recent data indicates that surgical resection may bring a benefit for select patients with metastatic gastric / esophagogastric junction cancer. However, no data obtained in randomized trials is available up to now. The current RENAISSANCE trial investigates this long-lasting question about the role of surgical intervention in limited-metastatic gastric / esophagogastric junction cancer. Methods: This is a prospective, multicenter, randomized, investigator initiated phase III trial. In this study, previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) will receive 4 cycles of FLOT (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2,600 mg/m²), and if Her2+ with trastuzumab. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will be randomized. The primary endpoint is overall survival; main secondary endpoints are quality of life parameters as assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 21 patients have been enrolled. EudraCT: 2014-002665-30. Clinical trial information: NCT02578368.

Defining two prognostic groups of metastatic gastric cancer: FLOT3 trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

4070 Background: A prognostic model for metastatic gastric cancer has not been established yet. Methods: Pts with untreated gastric cancer were prospectively stratified into 3 groups: operable (OD), limited metastatic (LD), or extensive metastatic (ED) disease using a predefined algorithm and treated with 5-FU, oxaliplatin, leucovorin and docetaxel (FLOT). LD was defined as having all of the following: distant intra-abdominal lymph node metastases and/or a maximum of 1 organ involved in metastatic disease (distant extra-abdominal lymph node metastases were considered as 1 organ), normal serum alkaline phosphatase, < 5 liver lesions, no clinically apparent peritoneal carcinomatosis, no lymphangiosis carcinomatosa of the lung or malignant pleural effusion, and ECOG ≤ 1. All other metastatic pts were ED. Pts with OD received 4 preoperative cycles of FLOT and were operated (D2-resection) followed by 4 postoperative cycles. Pts with LD received 8 cycles with surgery allowed for complete macroscopic resection. Pts with ED received 8 cycles with surgery allowed for palliation only. The study had 80% power to detect a HR of 0.55 for overall survival in favor of the LD group (vs. ED group; 2-sided log-rank p=0.05). Results: A total of 252 pts (OD/LD/ED: 52/68/132) were included between Feb 2009 and Jan 2010 in 47 centers, of whom 239 pts were eligible. All 3 groups received a median of 8 cycles of FLOT. The primary endpoint of the study was met: median OS was 18.6 vs. 10.9 months in pts with LD vs. ED, respectively (HR 0.4; 95% CI, 0.28 – 0.63; p <0.001). Median OS in the OD group (not reached) was superior to LD and ED groups. There were also significant differences in the distribution of PFS according to group (p<0.001 for all comparisons). Surgical or local ablative treatment was conducted in 95.7%, 42.64%, and 5.4% in the OD, LD, and ED groups, respectively (p<0.001 for all comparisons). Grade 3/4 toxicities were similar among groups (70.6%, 72.1%, and 80.9%, respectively), but anemia, pain, and infection were significantly more frequent in ED pts. Conclusions: This simple clinical score was able to stratify pts with metastatic gastric cancer into different clinically relevant prognostic groups.