Gastric Gastroesophageal Junction Adenocarcinoma Research Articles

Biomarkers of response in patients with gastric/gastroesophageal junction adenocarcinoma (GEA) treated with telisotuzumab adizutecan.

490 Background: c-Met protein (MET protein) overexpression (OE) and MET amplification (amp) occur in several cancer types, including GEA, and are associated with poor prognosis. The c-Met–directed antibody-drug conjugate telisotuzumab adizutecan (ABBV-400) is being assessed in advanced solid tumors in an ongoing, first-in-human study (NCT05029882). Results showed promising antitumor activity and a tolerable safety profile in GEA (Strickler et al. ESMO 2024, 1439P). Here, we present our analysis on associations between c-Met OE, MET amp, and ctDNA-derived molecular response with clinical outcomes. Methods: c-Met expression was evaluated retrospectively in FFPE tissue (archival/fresh) collected at study screening using IHC (SP44 Ab clone) or whole transcriptomic RNA sequencing (Caris). Plasma ctDNA collected at baseline (BL) and cycle 3 day 1 (C3) was analyzed with the GuardantINFINITY assay. Molecular response (MR) was assessed using circulating tumor fraction (cTF), estimated on the basis of ctDNA variant allele frequencies in a 74-gene panel (Guardant360 CDx) and methylation signals (GuardantINFINITY methylome platform). MR was defined as a 50% decrease in cTF from BL. MET amp status was determined retrospectively by the Guardant Health algorithm. Radiographic response was assessed per RECIST v1.1. Results: Clinical data from 42 patients (pts) with advanced GEA were included in this biomarker analysis. There was a negative correlation between c-Met expression and tumor size change from BL (R=-0.59). Of 42 pts, 12 (29%) had tumors with MET amp per ctDNA analysis/local site reports, which was higher than the bioinformatic analysis of real-world data (Caris-ConcertAI linked RWD360 and PT360; ~3%). Concordance between c-Met expression per IHC and RNA was observed (R=0.75, p<10 -6 ). There were 12 responders; 7 (58%) had MET amp, and 5 (42%) did not. Responders had lower ctDNA percentage change from BL vs nonresponders (1.5-fold and 1.6-fold difference based on 74-gene and methylation panel, respectively). Pts with MR had a greater decrease in tumor size from BL vs those without MR. A positive correlation between change in ctDNA levels (BL to C3) and change in tumor size was observed using the 74-gene panel and methylation panel (R=0.73 and 0.69, respectively). Additional biomarker analyses focused on the association between MET and other key biomarkers relevant in GEA will be discussed. Conclusions: In pts with advanced GEA treated with telisotuzumab adizutecan, c-Met OE/ MET amp and ctDNA-based MR were associated with enhanced antitumor activity. Compared with real-world data, MET amp was enriched in this study population. Phase 2 studies will continue to explore c-Met OE and MET amp prevalence and their potential predictive value with other biomarkers in a clinically representative population. Clinical trial information: NCT05029882 .

FG-M108 plus capecitabine and oxaliplatin (CAPOX) for first-line treatment of CLDN18.2+/HER2- advanced gastric/gastroesophageal junction adenocarcinoma (GC): Update results of a phase I/II trial to determine RP2D.

431 Background: There exists unmet need for previously untreated pts with CLDN18.2+/HER2- advanced GC. FG-M108, an mAb specifically targeting CLDN18.2 and exhibiting enhanced ADCC activity, has the potential to benefit these pts. Methods: This phase I/II trial evaluated safety, pharmacokinetics and preliminary antitumor activity of FG-M108 plus CAPOX in previously untreated pts with CLDN18.2+/HER2- advanced GC, where FG-M108 was administered intravenously at 300 mg/m 2 or 600 mg/m 2 Q3W. Here we compare results of FG-M108 at 300mg/m 2 (Cohort A) with 600mg/m 2 (Cohort B) to establish RP2D. Results: As of August 28, 2024, 63 pts with CLDN18.2+ (IHC 1/2/3+≥10%) GC were treated, 70% of whom had CLDN18.2 Medium-High expression (CMH, IHC 2/3+≥40%). Baseline characteristics were comparable between Cohorts A & B. Increasing the FG-M108 dosage did not result in a higher incidence or severity of treatment-related adverse events (TRAE) overall. However, nausea and vomiting, identified as CLDN18.2 on-target toxicities, were significantly more frequent and severe in Cohort B compared to Cohort A.When 300 or 600 mg/m² of FG-M108 was administered intravenously Q3W, serum trough concentration exceeded the target drug concentration predicted by in vitro ADCC activity. The 300 mg/m² dose is expected to provide sufficient drug exposure as the effective dose.Moreover, in Cohort A, pts with CMH expression had a confirmed ORR of 78% (unconfirmed ORR=81%) and a median PFS of 11.0 months（95%CI 6.9-12.7）, significantly better than those in Cohort B. Based on safety, PK and efficacy trends, the RP2D was determined to be FG-M108 at 300mg/m 2 plus CAPOX. Conclusions: FG-M108 plus CAPOX had a manageable safety profile and promising antitumor activity in GC, with RP2D at 300mg/m 2 . A phase III trial is ongoing to confirm the efficacy of FG-M108 at 300mg/m 2 plus CAPOX as first-line treatment (NCT06177041). Clinical trial information: NCT04894825 . Cohort A n=52 Cohort B n=11 CMH % 71 64 Primary lesion-Stomach % 92 100 Metastatic organs ≥3 % 27 9 ORR/DCR with CMH % 81/97 57/86 PFS/DOR with CMH months 11.0/9.9 5.5/4.2 ≥G3 TRAE % 37 18 TRAE-Nausea % / ≥G3 Nausea % 38/2 64/9 TRAE-Vomiting % / ≥G3 Vomiting % 23/2 73/9

Envafolimab in combination with lenvatinib and albumin paclitaxel for previously treated advanced GEJ adenocarcinoma: Latest analysis of a phase II, two-cohort study.

375 Background: The combination of first-line chemotherapy and PD-1 has emerged as a standard treatment, enhancing the efficacy in advanced gastric/gastroesophageal junction (GEJ) cancer. The efficacy of the combination of second-line chemotherapy and PD-1/PD-L1 remains unclear. This study aims to observe the efficacy of Envafolimab (PD-L1 inhibitor ) plus tyrosine kinase inhibitors (TKIs) and second-line chemotherapy in the treatment of patients (pts) with advanced GEJ adenocarcinoma. Methods: Eligible pts with HER2-negative, microsatellite stable (MSS), advanced GEJ adenocarcinoma were enrolled in this study. Pts who never received PD-1 or PD-L1 inhibitors before would assign into Group A. Pts in Group B have failed first-line PD-1 antibody combined chemotherapy, with optimal efficacy as or above stable disease (SD). Pts in both groups received Envafolimab (200mg, hypodermic injection, days 1, 15, Q4W) combined with Lenvatinib (8mg/12mg, po, once a day) and albumin paclitaxel (100mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or pts refusal to continue treatment. The primary endpoint was objective response rate(ORR) per iRECISTv1.1, and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: From Oct 2022 to Apr 2024, 32 pts were enrolled. Both groups enrolled 16 pts equally, and 15 pts of each group were evaluable for efficacy analysis. The average ages were 60.07 ± 11.73 y and 50.13 ± 12.18 y in group A and B respectively. In group A, 7 pts had been tested for PD-L1 status, of which 2 (13.3%) was positive and 5 (33.3%) were negative. PD-L1 status was negative in 5(33.3%) pts, positive in 9 (60.0%), and untested in 1(6.7%) in group B. As of Sep 14, 2024, The ORR was 60.0% (9/15) in group A and 46.7% (7/15) in group B. The DCR was 100.0% (15/15) in both groups. After a median follow-up of 17.0 mo (IQR: 8.0-18.8) in group A, the mPFS was 8.2 mo (95% CI = 6.1-10.4), and the mOS was 14.8 mo(95% CI = 7.4-22.2). With median follow-up of 9.0 mo (IQR: 6.1-16.2) in group B, the mPFS was 5.9 mo (95% CI= 3.8-8.1) and the mOS was 11.5 mo (95% CI = 3.1-19.9). Overall incidences of adverse events (AEs) of any grade was 100% (30/30), and 80.0% (24/30) pts had ≥ grade 3 AEs during treatment. Most treatment-related adverse events (TRAEs) of grade ≥3 included decreased neutrophil count (73.3%), decreased leukocyte count (63.33%), Anemia (10%), febrile neutropenia (6.67%). Conclusions: In pts of advanced gastric cancer who have previously received PD-1 inhibitors or not, this second-line combination therapy demonstrates promising preliminary effects. Pts who have not previously received ICIs might benefit more from this combination therapy. Clinical trial information: NCT06030934 .

A phase II study of FOLFOX combined with nab-paclitaxel in the treatment of metastatic or advanced unresectable gastric, gastroesophageal junction adenocarcinoma: a Big Ten Cancer Research Consortium trial.

Doublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Previously used anthracycline-based triplet regimens are no longer used routinely due to toxicity and lack of superior efficacy. We hypothesized that the addition of nab-paclitaxel to FOLFOX (FOLFOX-A) would induce higher efficacy and better tolerability. Eligible patients with chemotherapy-naïve advanced unresectable HER2-negative gastric or GEJ adenocarcinoma were enrolled in this phase II single-arm trial of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46-48 hours) + nab-paclitaxel (150 mg/m2) every 14 days of a 28-day cycle. Evaluable disease according to RECIST v1.1 for solid tumors was required. The primary endpoint was the objective response rate. Simon's optimal 2-stage design was used to test 5% versus 20% response rate with 90% power and 10% one-sided type I error rate. The study enrolled 39 patients. Median age was 63 (range 20-80) years, 30 (77%) were male, 34 (94%) were White, and 21 (57%) had gastric tumors. The median number of cycles completed was 4.5 (range: 0-36), and 25 patients required dose reductions or discontinuation of at least one component due to toxicity. Of the 38 patients evaluable for response, 15 (42.9%) had complete/partial response (CR/PR) as the best response, and 13 (37.1%) had stable disease. progression-free survival (PFS) and OS data were available for 38 patients, with a median follow-up duration of 27 months (range: 18.2-51.9 months for censored patients). Median PFS was 6.6 months (95% CI: 5.6-12.9), with 31.0% (95% CI: 18.4%-52.4%) 12-month PFS rate. The median OS was 10.5 months (95% CI: 8.8-20.7), 12-month OS rate was 44.7% (95% CI: 31.4%-63.7%). Treatment-related grade 3-4 toxicities included peripheral sensory neuropathy and anemia (18.4% each), neutropenia (15.8%), and diarrhea and lymphopenia (7.9% each). FOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.

1439P ABBV-400, a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced gastric/gastroesophageal junction adenocarcinoma (GEA): Results from a phase I study

1439P ABBV-400, a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced gastric/gastroesophageal junction adenocarcinoma (GEA): Results from a phase I study

Updated results of perioperative PD-1 antibody toripalimab plus FLOT chemotherapy for locally advanced resectable gastric or gastro-esophageal junction adenocarcinoma: A one-arm open-table phase II trial.

e16128 Background: Perioperative chemotherapy is the standard treatment for resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. Immune checkpoint inhibitors have activity in advanced gastric/GEJ cancer. This trial to assess the efficacy of the addition of toripalimab to FLOT for resectable patients and explore the immune microenvironment prospectively related to treatment response of neoadjuvant immunotherapy by multiplex immunohistochemistry. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥ cT2 or cN+) were enrolled to receive 4 pre- and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-Fu 2600 mg/m2, q2w). The primary endpoint were 3-year disease-free survival rate, overall survival and pathological complete response rate (pCR). Planned sample size of 36 operated patients. if the pCR rate is greater than 16% (n = 6), an additional 20 cases will be added. Multiplex immunohistochemistry is used to quantify in situ biomarker at subcellular resolution. Results: Study accrual completed at August 2022, 55 patients were enrolled, 40M/15F, age 57 (28-76), ECOG 0 (39) and 1 (16). 4 patients had not received surgery were excluded from efficacy analysis (Three patients withdrew consent after two treatment cycles and one refused surgery after 4 cycles pre-operative treatment). Fifty-one had completely neoadjuvant treatment and received surgery. Pathological response was TRG 0/ 1/ 2/ 3 in 10/ 6/ 21/ 14 patients with pCR seen in 10 (19.6%). Major pathologic response (TRG 0 and 1) was seen in 16 (31.4%) patients. At 36.6 (17.6-57.8) months follow up, the median disease-free survival (DFS) and overall survival (OS) were not reached for all patients. DFS rate at 1, 2, and 3 year is 78.4%, 56.9%, and 54.3%. OS rate at 1, 2, and 3 year is 94.1%, 69.5%, and 65.2%. Compared with TRG 2 or 3, patients with MPR showed significant longer survival (p = 0.01). Twenty-four patients underwent immune microenvironment analysis on their pre-treatment specimens by multiplex immunohistochemisty. Compared with TRG 2 or 3 (n = 11), NK cells with positive CD56 expression in tumor parenchyma microenvironment in patients with MPR (n = 13) were significant decreased (p = 0.024). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate in patients with resectable gastric/GEJ adenocarcinoma. MPR rate and NK cells in tumor microenvironment have a predictive on therapeutic efficacy, with deserves further study. Clinical trial information: NCT04354662 .

Envafolimab in combination with lenvatinib and albumin paclitaxel for previously treated advanced gastric/gastroesophageal junction adenocarcinoma: Preliminary analysis of a phase II, two-cohort study.

e16039 Background: The combination of first-line chemotherapy and PD-1 has emerged as a standard treatment, enhancing the efficacy in advanced gastric/gastroesophageal junction (GEJ) cancer. The efficacy of the combination of second-line chemotherapy and PD-1/PD-L1 remains unclear. This study aims to observe the efficacy of Envafolimab plus tyrosine kinase inhibitors (TKIs) and second-line chemotherapy in the treatment of patients with advanced GEJ adenocarcinoma. Methods: This prospective, open-label, phaseⅡ, two cohort study was conducted to assess the efficacy and safety of Envafolimab-based therapy in patients experiencing progression after initial first-line treatment. Eligible patients with HER2-negative, microsatellite stable (MSS), advanced GEJ adenocarcinoma were consecutively enrolled and assigned into cohort A or cohort B, according to whether they received PD-1 inhibitors in the first-line treatment. Patients in both cohorts received Envafolimab (200mg, hypodermic injection, days 1 and 15, Q4W) combined with Lenvatinib (8mg/12mg, po, once a day) and albumin paclitaxel (100mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or patients refusal to continue treatment. The primary endpoint was objective response rate(ORR) per iRECIST v1.1, and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. The efficacy and safety data in this analysis were from patients in cohort A who previously failed in first-line chemotherapy and did not receive PD-1 or PD-L1 inhibitors ever. Results: From October 2022 to June 2023, cohort A enrolled 16 patients, and 15 of them were evaluable for efficacy analysis. The average age was 58.87 ±11.81 years, 80% patients were male. 6 patients had been tested for PD-L1 status, of which 1 (16.7%) was positive and 5 (83.3%) were negative. As of Jan29, 2024, the median follow-up was 10.6 months (95%CI = 8.67-12.53), the median number of treatment cycles was 7 cycles (IQR: 5, 8). Based on the iRECIST v1.1, the ORR was 60.00% (90% CI = 35.96%-80.91%), the DCR was 100.00% (90% CI = 81.90%-100.00%). The median PFS (mPFS) was 8.23 months (90% CI =6.27-8.61), and the median OS (mOS) was 10.6 months (90% CI =8.79-12.15). Overall incidences of adverse events (AEs) of any grade was 100%, and 75.00% (n = 12) had ≥ grade 3 AEs during treatment. Most treatment-related adverse events (TRAEs) of grade ≥3 included neutrophil count (56.25%), decreased leukocyte count (37.5%). Conclusions: In patients of advanced gastric cancer who have not previously received PD-1/PD-L1 inhibitors, this second-line combination therapy demonstrates promising preliminary effects. Clinical trial information: NCT06030934 .

Safety and Efficacy of Treatment with/without Ramucirumab in Advanced or Metastatic Cancer: A Meta-Analysis of 11 Global, Double-Blind, Phase 3 Randomized Controlled Trials.

Ramucirumab, as a vascular endothelial growth factor receptor-2 inhibitor, was first approved in 2014 for treated advanced or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma. This study deeply analyzed the efficacy and safety of advanced or metastatic cancer treated with ramucirumab, which included 11 global, double-blind, phase 3 randomized controlled trials with a total of 7410 patients. Subgroup analysis based on different cancer types showed that standard regimens plus ramucirumab significantly increased progression-free survival and overall survival compared with placebo groups in patients with advanced non-small-cell lung cancer (NSCLC), hepatocellular carcinoma, gastric cancer, or GEJ adenocarcinoma. Although a higher proportion of patients achieved overall response and disease control than those treated with placebo, the overall response was not statistically significant between the two groups in advanced NSCLC. Grade 3 or worse treatment-emergent adverse events (TEAEs) that occurred in at least 5% of patients were neutropenia (30.5% in the ramucirumab group vs. 23.5% in the placebo group), leucopenia (14.8% vs. 9.2%), weight decreased (14.2% vs. 8.0%), myalgia (11.7% vs. 7.7%), fatigue (10.9% vs. 7.7%), hypertension (9.2% vs. 2.3%), and anaemia (6.2% vs. 7.7%). In the TEAEs of special interest, the ramucirumab group had a significantly higher incidence of bleeding (mainly grade 1-2 epistaxis and gastrointestinal bleeding), hypertension, proteinuria, liver injury/failure (grade 1-2), venous thromboembolism (grade 1-2), and gastrointestinal perforation (grade ≧3) than the control group.

Nivolumab in gastric/gastroesophageal junction cancer: real-world data from UK Early Access to Medicines Scheme.

Aim: This study provides real-world insight into patient profile, clinical effectivenessand health-related quality of lifeamong patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma treated with nivolumab. Materials & methods: Data werecollected from medical records of patients with advanced GEJ adenocarcinoma treated with nivolumab in a UK Early Access to Medicines Schemeand from the patient-reported EuroQoL five dimensions questionnaire. Results: Evaluable patients (n=113; median age 62years) were predominantly male (76.1%), White (87.4%) andwith GEJ adenocarcinoma (61.9%). Median follow-up was 2.8months. The 6-month progression-free survivaland overall survival were 31.6and 56.7%, respectively. Mean EuroQoL five dimensions questionnaire index utility scores at baseline, 8, 16and 24weeks were 0.795, 0.831, 0.870and 0.793, respectively. Conclusion: Progression-free survival was consistent with trial results and health-related quality of life remained stable over time.

Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial

We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was progression-free survival (PFS) with 80% power to detect a hazard ratio (HR) of 0.71 (one-sided α = 0.15). Secondary end points included evaluation of response and overall survival (OS); an exploratory ramucirumab exposure-response analysis was undertaken. Of 168 randomized patients, 52% of tumors were located in the stomach/GEJ and 48% in the esophagus. The trial did not meet the primary end point of PFS [6.4 versus 6.7 months, HR 0.98 (95% confidence interval 0.69-1.37)] or the secondary end point of OS (11.7 versus 11.5 months) in the intent-to-treat (ITT) population. Objective response rates (45.2% versus 46.4%) were similar between arms. Most Grade ≥3 toxicities did not differ significantly between arms, yet premature discontinuation of FOLFOX and ramucirumab (for reasons other than progressive disease) was more common among ramucirumab- versus placebo-treated patients. In an exploratory analysis that censored for premature discontinuation, the HR for PFS favored the ramucirumab arm (HR 0.76), particularly in patients with gastric/GEJ cancer. An exploratory exposure-response analysis indicated that patients with higher ramucirumab exposure had longer OS. The addition of ramucirumab to front-line mFOLFOX6 did not improve PFS in the ITT population. NCT01246960.

Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial.

ABSTRACT This phase II trial examined the addition of ramucirumab, a vascular endothelial growth factor receptor-2 monoclonal antibody, to mFOLFOX6 as front-line therapy for patients with advanced gastric/GEJ or esophageal adenocarcinoma. A survival benefit was not observed in the ITT population, but an exploratory analysis suggested a potential benefit for ramucirumab in the gastric/GEJ cancer subgroup. Background We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). Patients and methods Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was progression-free survival (PFS) with 80% power to detect a hazard ratio (HR) of 0.71 (one-sided α = 0.15). Secondary end points included evaluation of response and overall survival (OS); an exploratory ramucirumab exposure–response analysis was undertaken. Results Of 168 randomized patients, 52% of tumors were located in the stomach/GEJ and 48% in the esophagus. The trial did not meet the primary end point of PFS [6.4 versus 6.7 months, HR 0.98 (95% confidence interval 0.69–1.37)] or the secondary end point of OS (11.7 versus 11.5 months) in the intent-to-treat (ITT) population. Objective response rates (45.2% versus 46.4%) were similar between arms. Most Grade ≥3 toxicities did not differ significantly between arms, yet premature discontinuation of FOLFOX and ramucirumab (for reasons other than progressive disease) was more common among ramucirumab- versus placebo-treated patients. In an exploratory analysis that censored for premature discontinuation, the HR for PFS favored the ramucirumab arm (HR 0.76), particularly in patients with gastric/GEJ cancer. An exploratory exposure–response analysis indicated that patients with higher ramucirumab exposure had longer OS. Conclusion The addition of ramucirumab to front-line mFOLFOX6 did not improve PFS in the ITT population. Clinicaltrials.gov identifier NCT01246960.

Paclitaxel, 5-fluorouracil, and cisplatin (PFC) combination in patients (pts) with localized or advanced gastric-gastroesophageal junction adenocarcinoma (G-GEJA): A monoistitutional experience.

e14678 Background: PFC is effective in G-GEJA, both preoperatively with 20% pCR rates after chemoradiotherapy (Ajani JCO 2005) and in advanced disease, with 34% OR rates (Jin JCO 2007). We report o...