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5024 Background: The OSPREY clinical trial was a phase 2/3 prospective study of prostate specific membrane antigen (PSMA) PET/CT using piflufolastat F 18. Piflufolastat F 18 (aka 18F-DCFPyL or PyL) is a novel PSMA-targeting radiopharmaceutical approved for imaging of PCa pts both at initial staging and for disease recurrence. Here we describe SUV results by biopsy status, baseline PSA levels, and Gleason score (GS). Methods: Piflufolastat F 18-PET/CT was evaluated in men with NCCN high-risk PCa scheduled to undergo radical prostatectomy with pelvic lymphadenectomy (RP-PLND) (Cohort A) and men with radiologically suspected recurrent/metastatic PCa (Cohort B). A single IV dose of 9 mCi (333 MBq) of piflufolastat F 18 was administered followed by PET/CT acquisition 1-2 hours later. Piflufolastat F 18 uptake in various lesion locations as defined by maximum and peak SUV (SUVmax, SUVpeak) were determined by three blinded, independent central readers for each tissue (e.g., bone, lymph nodes (LN), soft tissue). To measure SUVs, the reader placed a volume of interest (VOI) on each identified lesion. SUVmax was defined as the maximum single-voxel SUV within the VOI. SUVpeak within the VOI was defined as the average SUV within a fixed-sized VOI (1 cm diameter sphere), representing the cluster with the highest average SUV. Results: 345 men underwent piflufolastat F 18-PET/CT. Cohort B (n = 93evaluable) SUVmax and SUVpeak were significantly higher for biopsy positive (+)(one biopsy lesion/pt) when compared to biopsy negative (-) lesions from bone and LN. SUVpeak for biopsied bone and LN (Cohort B) appeared to increase with rising baseline PSA. In high-risk PCa pts, SUVpeak for prostate (Cohort A; n = 252 evaluable) increased with baseline PSA and were highest for GS 9-10 (Table). Conclusions: Piflufolastat F 18-PET/CT uptake was significantly higher in biopsy + lesions and increased with baseline PSA. Prostate SUVpeak was highest for GS 9-10. Clinical trial information: NCT02981368. [Table: see text]

35 Background: The OSPREY clinical trial was a phase 2/3 prospective study of prostate specific membrane antigen (PSMA) PET/CT using piflufolastat F 18. Piflufolastat F 18 (aka 18F-DCFPyL or PyL) is a novel PSMA-targeting radiopharmaceutical approved for imaging of PCa pts both at initial staging and for disease recurrence. Here we describe SUV results by biopsy status, baseline PSA levels, and Gleason score (GS). Methods: Piflufolastat F 18 -PET/CT was evaluated in men with NCCN high-risk PCa scheduled to undergo radical prostatectomy with pelvic lymphadenectomy (RP-PLND) (Cohort A) and men with radiologically suspected recurrent/metastatic PCa (Cohort B). A single IV dose of 9 mCi (333 MBq) of piflufolastat F 18 was administered followed by PET/CT acquisition 1-2 hours later. Piflufolastat F 18 uptake in various lesion locations as defined by maximum and peak SUV (SUVmax, SUVpeak) were determined by three blinded, independent central readers for each tissue (e.g., bone, lymph nodes (LN), soft tissue). To measure SUVs, the reader placed a volume of interest (VOI) on each identified lesion. SUVmax was defined as the maximum single-voxel SUV within the VOI. SUVpeak within the VOI was defined as the average SUV within a fixed-sized VOI (1 cm diameter sphere), representing the cluster with the highest average SUV. Results: 345 men underwent piflufolastat F 18-PET/CT. Cohort B (n = 93 evaluable) SUVmax and SUVpeak were significantly higher for biopsy positive (+) (one biopsy lesion/pt) when compared to biopsy negative (-) lesions from bone and LN. SUVpeak for biopsied bone and LN (Cohort B) appeared to increase with rising baseline PSA. In high-risk PCa pts, SUVpeak for prostate (Cohort A; n = 252 evaluable) increased with baseline PSA and were highest for GS 9-10 (Table). Conclusions: Piflufolastat F 18-PET/CT uptake was significantly higher in biopsy + lesions and increased with baseline PSA. Prostate SUVpeak was highest for GS 9-10. Clinical trial information: NCT02981368. [Table: see text]

TPS187 Background: PSMA is a transmembrane glycoprotein overexpressed in prostate cancer (PC) and further upregulated in castrate resistant disease. 1095 is a novel PSMA-targeted small molecule radioligand therapeutic that binds to the extracellular domain of PSMA selectively with high affinity, internalized, and delivers a targeted lethal radiation dose to PC cells. 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown robust diagnostic performance for detecting recurrent and metastatic PC. In the ARROW study, pts must demonstrate 18F-DCFPyL avidity prior to 1095 treatment. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at multiple sites in the US and Canada. Eligible male pts must have metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional doses administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Due to the COVID-19 pandemic, enrollment was halted in April 2020 but is reopening in October 2020. Clinical trial information: NCT03939689.

32 Background: Conventional imaging and bone scintigraphy are suboptimal modalities for identifying PCa. PSMA-based imaging is highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of PCa. The diagnostic performance, detection rate, and potential impact of 18F-DCFPyL on staging of pts with high- risk PCa have been previously reported. Here we report on the impact of 18F-DCFPyL on staging of pts with PCa recurrence or metastases on conventional imaging. Methods: 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging (CT, MRI) or whole-body bone scintigraphy and in whom at least one lesion was deemed amenable to biopsy. A single dose of 9 mCi (333 MBq) of 18F-DCFPyL was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. Based on TNM staging: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) and other visceral organs/soft tissue (M1c), 18F-DCFPyL-PET/CT detection rates including lesion counts were systematically analyzed. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: In this study, 82 (70%) patients had baseline radiographic M1 stage disease (14 patients with M1a, 50 patients with M1b, 18 patients with M1c) and 33 (28%) patients were M0 stage at baseline by central conventional imaging review; two patients were unevaluable. 18F-DCFPyL-PET/CT up-staged 58% (19/33) of pts from M0 to M1, of whom 91% (10/11) who underwent an extra-pelvic biopsy were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a. Of the patients who were staged M1 at baseline, 18F-DCFPyL-PET/CT upstaged 16% (10/64; M1a to M1b or M1c: n = 4; M1b to M1c: n = 6) of pts to a higher M1 sub-stage and down-staged 22% (18/82) to M0. Conclusions: 18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease. These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging. Clinical trial information: NCT02981368.

TPS5596 Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689 .

4514 Background: Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. These pts may benefit more from another, non-cross resistant chemotherapy backbone regimen. This trial evaluates the addition of Ram to FOLFIRI as second line treatment. Methods: This is a multicenter, randomized, investigator initiated, phase II trial. Pts with GEA who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomized 2:1 to either FOLFIRI plus Ram every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus Ram every two weeks (Arm B). Major endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and toxicity. Results: 111 pts (median age 61 years, 65% of pts had prior docetaxel therapy) were enrolled and 110 analyzed within intention to treat population (ITT, Arm A, 72; Arm B, 38). In the ITT, there was no significant difference in median OS (A, 6.8 vs. B, 7.6 months, HR 0.94, p = 0.77) and median PFS (A, 4.6 vs. B, 3.6 months, HR 0.72, p = 0.12). For pts with prior docetaxel use (71/110), median PFS was A, 4.3 vs. B, 2.0 months, HR 0.49, p = 0.008 and median OS was A, 7.5 vs. B, 6.4 months, HR 0.71, p = 0.25. In 101 pts with tumor assessment and included in the response analysis, ORR and DCR was 23% and 65% in Arm A and 11% and 60% in Arm B, respectively. 67 pts assessable for response were pre-treated with docetaxel. In these pts, ORR was 24% in Arm A and 9% in Arm B. Disease control rate (DCR) was 67% and 41% for Arm A and B respectively. Both therapies were similarly tolerable, final safety results will be shown. Conclusions: The RAMIRIS trial demonstrated feasibility of the combination of FOLFIRI and Ram. With a response rate of 24% and a median PFS of 4.3 months, docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial, which is currently ongoing. Clinical trial information: NCT03081143 .

9 Background: Current imaging modalities are suboptimal for the initial staging of men at risk of harboring occult metastatic prostate cancer (PCa). PSMA-based imaging is considered highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of pts with high risk PCa. The diagnostic performance of 18F-DCFPyL regarding regional and distant metastases has been previously reported. Here we report on detection rates and the resulting impact 18F-DCFPyL may have on staging of pts with high risk PCa. Methods: 18F-DCFPyL PET/CT was evaluated in 252 men with high-risk PCa who were planned for radical prostatectomy with lymphadenectomy (RP-PLND). 9 mCi (333 MBq) of 18F-DCFPyL was administered 1-2 hours prior to PET/CT. Based on TNM staging, 18F-DCFPyL PET/CT detection rates including lesion counts were systematically analyzed: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) & other visceral organs/soft tissue (M1c). Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: At study entry, 97% and 99% of all evaluable pts had no known nodal or metastatic disease, respectively, based on standard cross-sectional imaging. Of these, 18F-DCFPyL PET/CT staged 37 (14.7%) pts with N1 disease and 27 (10.7%) pts with M1 disease (1 [0.4%] M1a, 23 [9.1%] M1b, and 3 [1.2%] M1c). In total, 56 (22%) of patients were upstaged to N1 or M1 disease by 18F-DCFPyL. The positive predictive value of 18F-DCFPyL based on histopathologic validation for pelvic LNs was 86.7% (95% CI: 70, 95). Only one patient in Cohort A underwent a biopsy of their 18F-DCFPyL detected M1 finding; histopathology confirmed the metastatic lesion in the spine to be a true positive. Conclusions: A total of 22% of pts with high-risk PCa planned for RP-PLND had regional or distant metastatic lesions detected on 18F-DCFPyL PET/CT. These results suggest the potential utility of 18F-DCFPyL PET/CT in the staging of men with newly diagnosed high risk PCa to develop optimized treatment paradigms. Clinical trial information: NCT02981368.

TPS260 Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689.

4023 Background: Ramucirumab as monotherapy and in combination with paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. For those pts, the benefit of a combination of ramucirumab and paclitaxel is unclear, and physicians would choose an irinotecan-based regimen as second line treatment. This provides a rationale for the evaluation of FOLFIRI + ramucirumab. Methods: This is a multicenter, randomized, investigator initiated, phase II trial, planned to include 111 pts with advanced GEA to receive 2:1 either FOLFIRI plus ramucirumab every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus ramucirumab every two weeks (Arm B). Primary endpoint is 6-months OS rate. This abstract displays interim results of safety and overall objective response (ORR) in docetaxel pre-treated group from up to 65 randomized pts. The results were needed to decide on conducting a subsequent phase III study. Results: 58 (A, 36; B, 22) pts were included in the safety analysis and 50 pts with tumor assessment in the response analysis. Main ≥ grade 3 adverse events were respectively in arms A/B: neutropenia (20%/22%), fatigue (6%/0%), diarrhea (8%/3%), and related SAEs (14% v 23%). Twenty-nine of 50 pts (58%) were pre-treated with docetaxel. In these pts, ORR was 30% in Arm A (5/17) and 8% (1/12) in Arm B. Disease control rate (DCR) was 65% and 50% for Arm A and B respectively. Conclusions: The interim safety analysis of the RAMIRIS trial has demonstrated feasibility of the combination of FOLFIRI and ramucirumab. Docetaxel pre-treated pts had higher ORR and DCR when ramucirumab is combined with FOLFIRI, instead of paclitaxel. EudraCT: 2015-005171-24. Clinical trial information: NCT03081143.

TPS5092Background: Accurate localization of sites of disease is essential for delivering optimal care to patients with prostate cancer. This is especially true for patients who may have distant dis...

Purpose This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. Patients and Methods Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 (FLO) every 2 weeks or fluorouracil 2,000 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2 weekly, and cisplatin 50 mg/m2 every 2 weeks (FLP). The primary end point was progression-free survival (PFS). Results Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively. Conclusion FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.

4 Background: There is a need for effective treatments in the second- or further line setting in advanced gastric cancer, especially for new agents. In the current trial we evaluated paclitaxel with RAD001 (everolimus) in patients with gastric carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Methods: This is a randomized, double-blind, multi-center phase III study. Patients with gastric carcinoma or adenocarcinoma of the esophagogastric junction which has progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomly assigned to receive Paclitaxel (80 mg/m2) on day 1, 8 and 15 plus placebo (arm A) or RAD001 (10mg daily, arm B) d1-d28, repeated every 28 days as 2nd, 3rd or 4thline therapy. Primary end point was overall survival (OS), secondary endpoints were best overall response, disease control rate, progression free survival (PFS) and toxicity. Results: 300 patients (median age: 62 years; median lines prior therapy: 2) were randomly assigned (Arm A, 150, Arm B, 150). Response rate (complete and partial response) was 8.0% (95%CI: 4.2%-13.6%) in the paclitaxel/RAD001 arm and 7.3% (95% CI: 3.7%-12.7%) in the paclitaxel/placebo arm (p = 0.4).There was no significant difference in median PFS (placebo, 2.07 vs. RAD001, 2.2 months, HR 0.88, p = 0.3) and median OS (placebo, 5.1 vs. RAD001, 6.1 months, HR 0.92, p = 0.48). Combination of paclitaxel and RAD001 was tolerable, but the placebo arm was associated with significantly less (any grade) mucositis (15.8% vs. 37.2%), fever (10.3% vs 20.7%), leukopenia (11.6% vs. 21.4%), neutropenia (13.0% vs. 27.6%) and thrombocytopenia (2.1% vs 14.5%). Conclusions: The addition of RAD001 to paclitaxel/RAD001 did not significantly improve outcomes in pretreated metastatic gastric or esophagogastric junction adenocarcinoma. Additional biomarker studies are planned to look for subgroups that may have a benefit. Clinical trial information: NCT01248403.

4016 Background: Pathological response can be a potent surrogate factor for efficacy of neoadjuvant chemotherapy. Data from our phase II/III study comparing perioperative FLOT with ECF(X) in resect...

4079 Background: Perioperative ECF is a standard treatment for localized gastric/OGJ adenocarcinoma. However, 5-year survival rate remains below 40%. The FLOT regimen is an effective combination with pathologic response rates in the 15% range. This phase III study compares both regimens in resectable stages. Methods: Pts are stratified by different baseline criteria and randomized to either 3 + 3 perioperative cycles of ECF (epirubicin 50 mg/m2, d1; cisplatin 60 mg/m², d1; 5-FU 200 mg/m², d1-d21, qd21) or 4 + 4 cycles of perioperative FLOT (docetaxel 50mg/m2, d1; 5-FU 2600 mg/m², d1; leucovorin 200 mg/m², d1; oxaliplatin 85 mg/m², d1, qd14). 5-FU can be replaced by capecitabine in the ECF-arm (ECX). Central pathology is performed. This is a preplanned safety analysis after 300 patients. Results: The ongoing studyhas enrolled 380 of planned 590 pts, so far. 305 pts were included in this analysis. Median age is 62 yrs; 78% of pts are male. The primaries were gastric in 44.9%, OGJ in 50.4% and not evaluable/documented in 4.7% of pts. 281 pts were eligible for safety analyses. Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT, respectively, 35.9% vs. 44.6% of pts (ECF/ECX vs. FLOT) started postoperative chemotherapy (ct) and 22.5% vs 33.1% received all planned cycles. Grade 3/4 neutropenia was observed in 28.0% of ECF/ECX and 45.3% of FLOT pts (p=.0026). Thromboembolic events occurred in 14.1% vs. 5.8% in pts with ECF/ECX vs. FLOT (p=.027). Serious adverse events occurred in 52.1% vs. 47.5% of pts with ECF/ECX vs. FLOT (p=.48). Preoperative delay/interruptions of ct were observed in 71.1% vs. 56.8% of pts with ECF/ECX vs. FLOT (p=.013). Dose modifications of preoperative ct were performed in 27.5% vs. 20.1% of treatment cycles with ECF/ECX vs. FLOT, respectively. 197 pts have undergone surgery so far. Severe surgical morbidity was similar in both arms (ECF/ECX, 19.8%; FLOT, 16.8%). Surgical mortality was observed in 4 and 2 pts with ECF/ECX and FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative FLOT is feasible and safe. Clinical trial information: NCT01216644.

4083 Background: Perioperative ECF is a standard treatment for localized gastric/OGJ adenocarcinoma. However, 5-year survival rate remain below 40%. The FLOT regime is an effective new combination with pathologic response rates in the 15% range. This phase II/III study compares both regimens in resectable stages. Methods: Pts are stratified by different baseline criteria and randomized to either 3 + 3 perioperative cycles of ECF (Epirubicin 50 mg/m2, d1 Cisplatin 60 mg/m², d1 5-FU 200 mg/m², d1-d21, qd21) or 4 + 4 cycles of perioperative FLOT (Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1, qd14). 5-FU can be replaced by Capecitabine in the ECF-arm (ECX). This is a preplanned toxicity analysis after 200 pts in order to decide whether to continue to a phase III trial. Results: 202 pts have been randomized so far. Median age is 62 yrs; 79% of pts are male. The Primaries were Gastric in 43.4%, OGJ in 53.2% and not evaluable/documented in 3.4% of pts. 190 pts were eligible for the safety analyses. Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT, respectively, and 68.7% vs. 66.0% of pts (ECF/ECX vs. FLOT) started postoperative chemotherapy (ct). Grade 3/4 side effects were observed in 52.1% of ECF/ECX and 59.6% of FLOT pts with no significant differences between arms regarding individual grade 3/4 toxicities. Thromboembolic events occurred in 14.5% vs. 8.5% in pts with ECF/ECX vs. FLOT (p=.25). Serious adverse events occurred in 60.3% vs. 39.7% of pts with ECF/ECX vs. FLOT. Preoperative delay/interruptions of ct were observed in 74.0% vs. 61.7% of pts with ECF/ECX vs. FLOT (p=.07). Dose modifications of preoperative ct were performed in 28.1% vs. 22.3% of treatment cycles with ECF/ECX vs. FLOT, respectively. 121 pts underwent surgery. Severe surgical morbidity was similar in both arms (ECF/ECX, 15.8%; FLOT, 14.1%). Surgical mortality was observed in 2 and 1 pts with ECF/ECX and FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative FLOT is feasible and safe. This supports the continuation of the trial as a phase III.

4090 Background: The utility of surgery for metastatic gastric cancer is debated. A prospective trial was performed to evaluate a prognostic model for selecting patients (pts) treated with systemic chemotherapy (ct) who may also be candidates for surgical intervention. Methods: Using a predefined algorithm pts with untreated gastric cancer were prospectively stratified into 3 groups: operable (OD), limited metastatic (LD), or extensive metastatic (ED) disease and treated with 5-FU, oxaliplatin, leucovorin and docetaxel (FLOT). LD was defined as: distant intra-abdominal lymph node metastases only or/and a maximum of 1 organ involved, normal serum alkaline phosphatase, < 5 liver lesions, no visible carcinomatosis (peritoneum or pleura), and ECOG ≤ 1. All other metastatic pts were ED. Pts with OD received 4 preoperative ct cycles followed by surgery and 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: 238 of 252 pts included were eligible (OD/LD/ED: 51/60/127). LD pts had distant lymph nodes only (41%), liver (22%), lung (17%), localized peritoneal involvement (7%), or others (13%). A median of 8 ct cycles was applied to all groups. Median OS was 22.9 vs. 10.7 months in pts with LD vs. ED, respectively (HR 0.37; 95% CI, 0.25 – 0.56; p

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. ...

4013 Background: Elderly patients (pts) with esophagogastric cancer often do not receive effective 3-drug combination therapies due to tolerability concerns. This study evaluates a 2- versus a 3-dr...

22033 Background: This study was conducted to assess the prognostic role of EGFR in metastatic gastric cancer (MGC), with a view towards the future introduction of anti-EGFR therapy for MGC. Method...

4544 Background: MMP-9 has been implicated in invasion and metastasis of cancer, but little is known about its prognostic role in patients (pts) with metastatic gastric cancer undergoing chemothera...

4545 Background: The combination of docetaxel, cisplatin, and fluorouracil (DCF) is clearly superior to CF in the treatment of patients (pts) with advanced gastric cancer (AGC). DCF is, however, associated with significant toxicity, including neutropenia, febrile neutropenia, diarrhea and mucositis. This study evaluated a biweekly, oxaliplatin-based modification of DCF. Methods: Pts with measurable, locally advanced or metastatic adenocarcinoma of the stomach or GE-junction and no prior chemotherapy received mFOLFOX (oxaliplatin 85 mg/sqm, leucovorin 200 mg/sqm, and fluorouracil 2.6 g/sqm via 24hr infusion) in combination with docetaxel 50 mg/sqm on day 1 every 2 weeks (FLOT-regimen). Prophylactic G-CSF was not administered. Overall response rate (RR) was the primary endpoint (power 80% to detect a RR of >40%) and toxicity profile the main secondary endpoint. The study was externally monitored according to GCP and data were reviewed by an independent safety board. Results: 59 pts (male, 41; female, 18) were enrolled. At the time of analysis, 53 pts were evaluable for toxicity and 51 pts for response. Median age was 60 (range, 29–76), median ECOG PS was 1, and almost all (93%) pts had metastatic disease. Of 51 pts, 2 had a CR and 25 pts attained a PR, adding to an overall RR of 53% (ITT-analysis). Stable disease was observed in 12 (23.5%) and progressive disease in 6 (11.8%) pts. Six (11.8%) pts were not evaluable for response. NCI-CTC grade 3 or 4 hematologic toxicity included leukopenia in 12 (22.6%), neutropenia in 23 (43%), and anemia in 2 (3.8%) pts. Febrile neutropenia was observed in 1 (1.9%) pt only. Other grade 3 or 4 toxicities included peripheral neuropathy in 4 (7.5%), nausea in 3 (5.7%), vomiting in 2 (3.8%) as well as diarrhea and fatigue in 5 (9.4%) pts each. No treatment related deaths were observed. Conclusions: FLOT is active and has a favorable toxicity profile in the treatment of pts with AGC. It may show activity also in perioperative treatment settings and may be considered as a useful treatment option for elderly pts. Survival data will be presented at the meeting. [Table: see text]

LBA4016 Background: Cisplatin-based chemotherapy is a standard option in advanced gastric cancer. However, treatment results have been unsatisfactory so far, with a time to progression (TTP) of 3 to 4 months and an overall survival (OS) of 6 to 9 months. In addition, treatment regimens are too intense and toxicity is considerable. The aim of this 2-arm randomized trial was to determine whether FLO prolongs TTP and reduces toxicity as compared to FLP. Methods: Patients (pts) were randomized to receive FLO: F 2600 mg/m2 24 h infusion, L 200 mg/m2, and oxaliplatin 85 mg/m2, every two weeks or FLP: F 2000 mg/m2 24 h infusion, L 200 mg/m2, weekly, and cisplatin 50 mg/m2, every two weeks. The primary end point was TTP. Main secondary endpoints included toxicity, time to treatment failure (TTF), and OS. Based on a planned sample size of 218 pts, the trial was designed to have an 80% power to detect an improvement in median TTP from 3.5 to 5.0 months (1-sided log-rank test; significance level 0.05). Results: 220 pts (FLO/FLP, 112/108) were randomized between Aug 2003 and Jan 2006. Median age was 64 yrs and median ECOG was 1. 162 pts (FLO, 80; FLP, 81) had disease progression and 25 pts (FLO, 18; FLP, 8) are still under treatment. Median TTP was 5.7 months for FLO and 3.8 months for FLP (log-rank p = 0.081, Wilcoxon p = 0.019). Median TTF was 5.3 months for FLO and 3.1 months for FLP (log-rank p = 0.028). Response to FLO (34%) was superior to FLP (27%), with 15% and 30% of pts having disease progression as best response to FLO and FLP, respectively (chi-square for trend p = 0.012). Median treatment duration was 4.3 months with FLO and 3 months with FLP. FLO was associated with significantly less NCI-CTC grade 1–4 leukopenia, nausea, alopecia, fatigue, and renal toxicity and FLP was associated with significantly less peripheral neuropathy (chi-square for trend p < 0.05). Severe adverse events related to treatment were less frequent with FLO (8.9%) as compared to FLP (18.6%; p = 0.046). Conclusions: FLO reduced toxicity and improved efficacy as compared to FLP. This leads us to consider FLO for future studies in combination with targeted drugs to further improve the outcome of pts with gastric cancer. No significant financial relationships to disclose.

4015 Background: To evaluate the potential role of oxaliplatin in the treatment of patients (pts) with advanced gastric cancer. Methods: Eligible patients had ECOG performance status (PS) 0–2, adeq...