Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR)
Abstract Background Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen i...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09623-z |
| _version_ | 1811235448610095104 |
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| author | Mélanie Dos Santos Justine Lequesne Alexandra Leconte Stéphane Corbinais Aurélie Parzy Jean-Marc Guilloit Sharmini Varatharajah Pierre-Emmanuel Brachet Marine Dorbeau Dominique Vaur Louis-Bastien Weiswald Laurent Poulain Corentin Le Gallic Marie Castera-Tellier Marie-Pierre Galais Bénédicte Clarisse |
| author_facet | Mélanie Dos Santos Justine Lequesne Alexandra Leconte Stéphane Corbinais Aurélie Parzy Jean-Marc Guilloit Sharmini Varatharajah Pierre-Emmanuel Brachet Marine Dorbeau Dominique Vaur Louis-Bastien Weiswald Laurent Poulain Corentin Le Gallic Marie Castera-Tellier Marie-Pierre Galais Bénédicte Clarisse |
| author_sort | Mélanie Dos Santos |
| collection | DOAJ |
| description | Abstract Background Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma. Methods GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles. For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4–6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4–10 weeks after surgery. Using a Simon’s two-stage design, up to 67 patients will be enrolled, including 23 in the first stage. Discussion Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes. Trial registration NCT04736485, registered February, 3, 2021. |
| first_indexed | 2024-04-12T11:52:07Z |
| format | Article |
| id | doaj.art-ecf3f3856bb641e9a8b19784d514a27f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T11:52:07Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-ecf3f3856bb641e9a8b19784d514a27f2022-12-22T03:34:09ZengBMCBMC Cancer1471-24072022-05-0122111010.1186/s12885-022-09623-zPerioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR)Mélanie Dos Santos0Justine Lequesne1Alexandra Leconte2Stéphane Corbinais3Aurélie Parzy4Jean-Marc Guilloit5Sharmini Varatharajah6Pierre-Emmanuel Brachet7Marine Dorbeau8Dominique Vaur9Louis-Bastien Weiswald10Laurent Poulain11Corentin Le Gallic12Marie Castera-Tellier13Marie-Pierre Galais14Bénédicte Clarisse15Clinical Research Department, UNICANCER, Centre François BaclesseClinical Research Department, UNICANCER, Centre François BaclesseClinical Research Department, UNICANCER, Centre François BaclesseDepartment of Medical Oncology, UNICANCER, Centre François BaclesseDepartment of Medical Oncology, UNICANCER, Centre François BaclesseDepartment of Surgery, UNICANCERCentre François BaclesseDepartment of Surgery, UNICANCERCentre François BaclesseClinical Research Department, UNICANCER, Centre François BaclesseDepartment of Pathology, UNICANCERCentre François BaclesseDepartment of Cancer Biology and Genetics, UNICANCERCentre François BaclesseUNICANCER, Centre François BaclesseUNICANCER, Centre François BaclesseClinical Research Department, UNICANCER, Centre François BaclesseClinical Research Department, UNICANCER, Centre François BaclesseDepartment of Medical Oncology, UNICANCER, Centre François BaclesseClinical Research Department, UNICANCER, Centre François BaclesseAbstract Background Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma. Methods GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles. For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4–6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4–10 weeks after surgery. Using a Simon’s two-stage design, up to 67 patients will be enrolled, including 23 in the first stage. Discussion Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes. Trial registration NCT04736485, registered February, 3, 2021.https://doi.org/10.1186/s12885-022-09623-zGastric cancerGastroesophageal junction cancerNeoadjuvant treatmentImmunotherapySpartalizumab |
| spellingShingle | Mélanie Dos Santos Justine Lequesne Alexandra Leconte Stéphane Corbinais Aurélie Parzy Jean-Marc Guilloit Sharmini Varatharajah Pierre-Emmanuel Brachet Marine Dorbeau Dominique Vaur Louis-Bastien Weiswald Laurent Poulain Corentin Le Gallic Marie Castera-Tellier Marie-Pierre Galais Bénédicte Clarisse Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR) BMC Cancer Gastric cancer Gastroesophageal junction cancer Neoadjuvant treatment Immunotherapy Spartalizumab |
| title | Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR) |
| title_full | Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR) |
| title_fullStr | Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR) |
| title_full_unstemmed | Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR) |
| title_short | Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR) |
| title_sort | perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil leucovorin oxaliplatin and docetaxel flot a phase ii study gaspar |
| topic | Gastric cancer Gastroesophageal junction cancer Neoadjuvant treatment Immunotherapy Spartalizumab |
| url | https://doi.org/10.1186/s12885-022-09623-z |
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