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Pathological Complete Response (PCR) to 5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT) ± Durvalumab (D) in Resectable Gastric and Gastroesophageal Junction Cancer (GC/GEJC): Subgroup Analysis by Region from the Phase 3 MATTERHORN Study

Authors
Yelena Y. Janjigian1, Salah-Eddin Al-Batran2, Zev A. Wainberg3, Eric Van Cutsem4, Daniela Molena5, Kei Muro6, Woo Jin Hyung7, Lucjan Wyrwicz8, Do-Youn Oh9, Takeshi Omori10, Markus Moehler11, Marcelo Garrido12, Sulene C.S. Oliveira13, Moishe Liberman14, Victor Castro Oliden15, Mehmet Bilici16, John F. Kurland17, Ioannis Xynos18, Helen Mann18, Josep Tabernero19

Affiliations

  1. Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;
  2. Institute of Clinical Cancer Research, Krankenhaus Nordwest, University Cancer Center, Frankfurt, Germany;
  3. Department of Gastrointestinal Medical Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;
  4. Department of Gastroenterology/Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium;
  5. Division of Thoracic Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA;
  6. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan;
  7. Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea;
  8. Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland;
  9. Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea;
  10. Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan;
  11. Research Center for Immunotherapy (FZI), Johannes Gutenberg-University Clinic, Mainz, Germany;
  12. Hemato-Oncology Department, SAGA Clinical Trial Centre and Universidad Mayor, Santiago, Chile;
  13. Clinical Oncology, The Clinical Research Center, Northern Riograndense League Against Cancer, Natal, Rio Grande do Norte, Brazil;
  14. Division of Thoracic Surgery, Department of Surgery, Centre Hospitalier de l'Université de Montréal, Centre de Recherche du CHUM, Montréal, Quebec, Canada;
  15. National Institute of Neoplastic Diseases (INEN), Lima, Peru;
  16. Department of Medical Oncology, Atatürk University Faculty of Medicine, Erzurum, Turkey;
  17. AstraZeneca, Gaithersburg, MD, USA;
  18. AstraZeneca, Cambridge, UK;
  19. Medical Oncology Department, Vall d’Hebron Hospital Campus & Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain

Introduction
FLOT was established as a perioperative therapy for GC/GEJC following the Phase 2/3 FLOT4 study conducted in Germany (Al-Batran et al, Lancet Oncol 2016). MATTERHORN (NCT04592913) showed a significant improvement in pCR with perioperative D + FLOT vs placebo (P) + FLOT in GC/GEJC at first interim analysis (Janjigian et al, ESMO Congress 2023). Subgroup analyses by region and country were completed to assess pCR rates with FLOT and benefit of D + FLOT across the global study population.

Methods
Participants (pts) with resectable GC/GEJC were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 plus FLOT Q2W on Days 1 and 15 for 4 cycles (2 doses of D or P and 4 doses of FLOT pre- and post-operative), followed by D 1500 mg or P on Day 1 Q4W for 10 cycles. Randomization was stratified by Asia vs non-Asia. pCR (Modified Ryan; central review) was assessed in prespecified (Asia) and post-hoc regional subgroups, including 6 countries with the highest numbers of randomized pts.

Results
Of 948 pts randomized globally, 180 pts (19%) were in Asia. pCR outcomes with FLOT in Asia were consistent with global outcomes. pCR rates were improved with D + FLOT vs P + FLOT in all regions (Table), despite some imbalances in baseline characteristics and numerical differences in pCR rates by geographic location. pCR rate with P + FLOT in the German subgroup (13%) was similar to FLOT in the FLOT4 study (16%). pCR with D + FLOT vs P + FLOT was improved across country subgroups. Similar trends across regional subgroups were observed for combined complete and near-complete response rate.

Conclusion
In MATTERHORN, pCR was consistently improved with perioperative D + FLOT across geographic regions. The study is ongoing for the primary objective of event-free survival.