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Pathological response guides adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in surgically resected gastro-oesophageal cancer (SPACE-FLOT): international cohort study. (PubMed, Br J Surg) - "Pathological response to neoadjuvant FLOT may guide the use of adjuvant FLOT, enabling personalized approaches to treatment."

Journal • Retrospective data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor

Efficacy and safety of perioperative durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma in Asia: A subgroup analysis of the MATTERHORN trial (ESMO Asia 2025) - P3 | "Consistent with global MATTERHORN results, D + FLOT improved efficacy vs P + FLOT with a manageable safety profile in Asian pts with resectable G/GEJ adenocarcinoma."

Clinical • Gastroesophageal Junction Adenocarcinoma • Oncology

Pembrolizumab and trastuzumab in combination with FLOT in the perioperative treatment of HER2-positive localized esophagogastric adenocarcinoma: Interim analysis of the phase II PHERFLOT/IKF-053 trial of the AIO study group (AIO STO 0321) (ESMO 2025) - P2 | "Perioperatively, FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) is preferred in resectable HER2-positive disease...All pts experienced adverse events (AEs); 48.4% had at least one grade 3 treatment-related (TR) serious AE, predominantly chemotherapy-related; grade 4 neutropenia was the only ≥ grade 4 TRAE. Table: 2095MO Pathological response n (%) Missing value due to withdrawal from surgery 1 (3.2%) Complete Response (pCR) - no tumor cells visible, but signs of regression 15 (48.4%) Subtotal Response (pSR) - morphologically intact neoplastic cells in 50% of tumor bed 6 (19.4%) Conclusions Perioperative FLOT plus P and T is feasible, with an expected safety profile and strong antitumor activity, suggesting superiority over current standards."

Combination therapy • IO biomarker • P2 data • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1

Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial). (ASCO 2024) - P3 | "ESOPEC (NCT02509286) is a multicenter prospective randomized trial comparing neoadjuvant CROSS (41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative FLOT (5-FU/ leucovorin/oxaliplatin/docetaxel) and surgery for the curative treatment of EAC... Perioperative FLOT improves survival in resectable EAC compared to neoadjuvant CROSS. Funding: The trial was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 264590883."

Clinical • Late-breaking abstract • P3 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology

FLOT Versus FLOT/Trastuzumab/Pertuzumab Perioperative Therapy of Human Epidermal Growth Factor Receptor 2-Positive Resectable Esophagogastric Adenocarcinoma: A Randomized Phase II Trial of the AIO EGA Study Group. (PubMed, J Clin Oncol) - "The addition of trastuzumab/pertuzumab to perioperative FLOT significantly improved pCR and nodal negativity rates at the price of higher rates of diarrhea and leukopenia."

Journal • P2 data • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Leukopenia • Oncology • Solid Tumor • HER-2

Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial. (PubMed, J Clin Oncol) - "Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression."

Journal • P2/3 data • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Pembrolizumab plus chemotherapy vs chemotherapy as neoadjuvant and adjuvant therapy in locally-advanced gastric and gastroesophageal junction cancer: The phase III KEYNOTE-585 study (ESMO 2023) - P3 | "Methods Patients (pts) with untreated, locally-advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W or pbo + chemo (cisplatin + capecitabine or cisplatin + 5-FU) for 3 cycles...In the FLOT cohort, pts were randomized 1:1 to pembro + docetaxel, oxaliplatin, leucovorin, and 5-FU, Q2W...Outcomes in the main + FLOT cohort are in the Table. Table: LBA74 Outcomes in main + FLOT cohort Efficacy Pembro + chemoN = 502 Pbo + chemoN = 505 Treatment difference (95% CI) Path CRa, % 13.0 (10.2-16.3) 2.4 (1.3-4.2) 10.6% (7.4-14.0) P<0.0001 Median EFS, mo (95% CI) 45.8 (35.9-NR) 25.7 (21.9-33.9) HR 0.81 (0.68-0.97) P=0.011 Median OS, mo (95% CI) 60.7 (51.5-NR) NR (45.7-NR) HR 0.93 (0.76-1.12) Safety Pembro + chemoN = 498 Pbo + chemoN = 503 NA Grade ≥ 3 drug-related AEs 67% 63% NA aIn first 987 pts randomized; HR, hazard ratio; NA, not applicable; NR, not reached Conclusions Neoadjuvant/adjuvant pembro + chemo followed by adjuvant pembro,..."

Clinical • Late-breaking abstract • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Neo-AEGIS (Neoadjuvant Trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): Final primary outcome analysis. (ASCO-GI 2023) - P3 | "Neo-AEGIS was designed as the first randomized clinical trial (RCT) to directly compare the multimodal CROSS regimen (carboplatin/paclitaxel, 41.4Gy radiation therapy) with a modified MAGIC (epirubicin, cisplatin (oxaliplatin), 5-FU (capecitabine)) regimen (pre-2018) and more latterly the FLOT (docetaxel, 5-FU, leucovorin, oxaliplatin) regimen... This RCT reveals no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy in the primary outcome of overall survival, notwithstanding greater proxy markers of local tumor response in the CROSS arm. Oncologic and operative outcomes were consistent with optimum modern benchmarks. These data strongly suggest non-inferiority and support equipoise in clinical decision making in modern practice."

Clinical • Esophageal Adenocarcinoma • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology

Final analysis of the phase III KEYNOTE-585 study of pembrolizumab plus chemotherapy vs chemotherapy as perioperative therapy in locally-advanced gastric and gastroesophageal junction cancer (ESMO-GI 2024) - P3 | "Methods Eligible pts with untreated, locally advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W or pbo + chemo (cisplatin + capecitabine or cisplatin + 5-FU) for 3 cycles...In the FLOT cohort, pts were randomized 1:1 to pembro or pbo + docetaxel, oxaliplatin, leucovorin, and 5-FU, Q2W...Outcomes in the main + FLOT cohort are in the table. Conclusions Efficacy and safety outcomes with neoadjuvant/adjuvant pembro + chemo followed by adjuvant pembro in pts with untreated, locally advanced resectable G/GEJ cancer at final analysis, were consistent with the prior analysis."

Late-breaking abstract • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase II study of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel for resectable esophageal squamous cell carcinoma: Survival analysis. (ASCO-GI 2026) - "Background: Based on the JCOG1109 trial, the combination of neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by esophagectomy has become the standard of care for resectable locally advanced esophageal squamous cell carcinoma (ESCC). After follow up, neoadjuvant FLOT therapy demonstrated acceptable OS and PFS. This regimen may be considered as a treatment option for resectable locally advanced ESCC. Clinical trial information: jRCTs031200094."

Clinical • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology

Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. (PubMed, N Engl J Med) - P3 | "Perioperative durvalumab plus FLOT led to significantly better event-free survival outcomes than FLOT alone among participants with resectable gastric or gastroesophageal junction adenocarcinoma. (Funded by AstraZeneca; MATTERHORN ClinicalTrials.gov number, NCT04592913.)."

Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Preoperative Chemoradiotherapy for Resectable Gastric Cancer. (PubMed, N Engl J Med) - P2/3 | "The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.)."

Journal • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study. (PubMed, J Clin Oncol) - P3 | "Participants with previously untreated, locally advanced, resectable gastric and gastroesophageal junction (G/GEJ) cancer were enrolled into the main (n = 804) and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT; n = 203) cohorts, and randomly assigned 1:1 to neoadjuvant and adjuvant pembrolizumab plus chemotherapy or placebo plus chemotherapy. Pembrolizumab plus chemotherapy continued to show improved outcomes in pathCR and a trend toward longer EFS versus placebo in the main and main plus FLOT cohorts. Efficacy and safety outcomes with perioperative pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in participants with untreated, locally advanced resectable G/GEJ cancer were consistent with previous analyses."

Journal • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Surrogate endpoints for survival in KEYNOTE-585: neoadjuvant/adjuvant pembrolizumab plus chemotherapy versus placebo plus chemotherapy for gastric or gastroesophageal junction adenocarcinoma. (PubMed, ESMO Open) - "These findings suggest a potential association between pCR, mPR, or pDS and survival in patients with locally advanced gastric or GEJ adenocarcinoma, although further validation is needed."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. (PubMed, Lancet) - P3 | "Perioperative durvalumab plus FLOT improved overall survival versus placebo plus FLOT and is a new standard treatment option for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma."

IO biomarker • Journal • P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • PD-L1

Pembrolizumab plus FLOT vs FLOT as neoadjuvant and adjuvant therapy in locally advanced gastric and gastroesophageal junction cancer: Interim analysis of the phase 3 KEYNOTE-585 study. (ASCO-GI 2024) - P3 | " In the FLOT cohort, patients (pts) with untreated, locally advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W (pembro gp) or pbo (pbo gp) Q3W for 3 cycles + FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) Q2W for 4 cycles... Neoadjuvant/adjuvant pembro + FLOT was feasible with no new safety concerns. PathCR and EFS favored pembro + FLOT vs pbo + FLOT in pts with untreated, locally advanced resectable G/GEJ cancer. Clinical trial information: NCT03221426."

Clinical • Metastases • P3 data • P3 data: top line • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

An open label phase 2 study of total neoadjuvant therapy (TNT) consisting of FLOT with pembrolizumab and short radiation for patients with locally advanced gastroesophageal junction adenocarcinoma (EPOC2301). (ASCO-GI 2026) - P2 | "Background: Perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) is the standard of care for resectable upper gastrointestinal adenocarcinoma, based on the FLOT4 and ESOPEC trials. The phase III MATTERHORN trial further demonstrated that adding durvalumab to FLOT (D-FLOT) improves event-free survival (EFS) in patients with resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma...Enrollment began in July 2025. The trial is funded by MSD and registered at ClinicalTrials.gov (NCT07018570)."

Clinical • Metastases • P2 data • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): Results from the GASPAR phase 2 study. (PubMed, Eur J Cancer) - P2 | "Spartalizumab combined with FLOT shows high efficacy as perioperative treatment in patients with resectable gastric cancer, and an acceptable safety profile."

Journal • P2 data • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Phase II study of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel for resectable esophageal squamous cell carcinoma. (ASCO-GI 2025) - "Funded by No funding sources reported Clinical Trial Registration Number: jRCTs031200094 Background: Based on the JCOG1109 trial, neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by surgery has become the standard of care for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Neoadjuvant FLOT therapy showed a promising pathological response with acceptable toxicities. It was noteworthy that the incidence of febrile neutropenia was relatively lower with compared to neoadjuvant DCF therapy. This regimen might be a treatment option for locally advanced ESCC."

Clinical • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology

Recurrence patterns in the prospective, randomized, controlled, multicenter phase III ESOPEC trial comparing perioperative chemotherapy with preoperative chemoradiotherapy in patients with esophageal adenocarcinoma. (ASCO 2025) - P3 | " Pts with cT1 cN+ cM0 or cT2-4a cNany cM0 EAC undergoing preoperative chemotherapy with FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) or preoperative chemoradiotherapy with CROSS (41.4Gy/carboplatin/paclitaxel) plus tumor resection from the ESOPEC trial were eligible... Perioperative chemotherapy with FLOT improves RFS and DMFS compared to preoperative chemoradiotherapy with CROSS in EAC. The prognosis of pts is determined by distant recurrence, which is less common after FLOT than CROSS. Treatment group comparisons regarding site of recurrence.* % calculated as 3-year cumulative incidence"

Clinical • P3 data • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Solid Tumor

A prospective, exploratory study of Retlirafusp alfa combined with FLOT as neoadjuvant therapy for patients with resectable adenocarcinoma of the esophagogastric junction (ChiCTR) - P2 | N=37 | Not yet recruiting | Sponsor: Xijing Hospital, Air Force Medical University; Xijing Hospital, Air Force Medical University

New P2 trial • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • HER-2 • PD-L1

Phase 1a/b Multi-Center Study of BPM31510IV Targeting Mitochondrial Metabolism/Warburg Effect as Monotherapy and Combination Chemotherapy in Solid Tumor Patients. (PubMed, Cancer Res Commun) - "BPM31510IV monotherapy and in combination with chemotherapy was safe, with preliminary evidence of anti-tumor activity. High plasma CoQ10 levels were achieved, inducing PD responses consistent with mitochondrial metabolic changes. These findings support continued clinical development of BPM31510IV."

Journal • Monotherapy • P1 data • Oncology • Solid Tumor

Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial. (PubMed, Lancet Gastroenterol Hepatol) - P3 | "Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise."

Journal • Metastases • P3 data • Cardiovascular • Esophageal Adenocarcinoma • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Oncology • Pulmonary Embolism • Respiratory Diseases • Uveal Melanoma

Perioperative FLOT(D) With Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) in Esophageal Cancer (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology

Pathological complete response (pCR) to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) with or without durvalumab (D) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Subgroup analysis by region from the phase 3, randomized, double-blind MATTERHORN study. (ASCO-GI 2024) - P3 | "In MATTERHORN, pCR was consistently improved with the addition of D to perioperative FLOT in GC/GEJC across geographic regions. The study is ongoing for the primary objective of event-free survival. Clinical trial information: NCT04592913."

Clinical • Late-breaking abstract • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor