Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial
Abstract Background The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-...
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| Language: | English |
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BMC
2023-03-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-10661-4 |
| _version_ | 1797864433042587648 |
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| author | Le Zhang Weixue Wang Shaohua Ge Hongli Li Ming Bai Jingjing Duan Yuchong Yang Tao Ning Rui Liu Xia Wang Zhi Ji Feixue Wang Haiyang Zhang Yi Ba Ting Deng |
| author_facet | Le Zhang Weixue Wang Shaohua Ge Hongli Li Ming Bai Jingjing Duan Yuchong Yang Tao Ning Rui Liu Xia Wang Zhi Ji Feixue Wang Haiyang Zhang Yi Ba Ting Deng |
| author_sort | Le Zhang |
| collection | DOAJ |
| description | Abstract Background The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients. Methods In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator’s choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety. Results From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9–72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4–11.5) and 12.5 months (95% CI, 3.7–21.3), respectively. Grade 3–4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3–4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred. Conclusion Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer. Trial registration ClinicalTrials.gov: NCT05025033, 27/08/2021. |
| first_indexed | 2024-04-09T22:52:56Z |
| format | Article |
| id | doaj.art-7d3883f1d343472e9b8e90882b72dd49 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T22:52:56Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7d3883f1d343472e9b8e90882b72dd492023-03-22T11:34:38ZengBMCBMC Cancer1471-24072023-03-0123111010.1186/s12885-023-10661-4Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trialLe Zhang0Weixue Wang1Shaohua Ge2Hongli Li3Ming Bai4Jingjing Duan5Yuchong Yang6Tao Ning7Rui Liu8Xia Wang9Zhi Ji10Feixue Wang11Haiyang Zhang12Yi Ba13Ting Deng14Department of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of GI Medical Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerAbstract Background The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients. Methods In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator’s choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety. Results From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9–72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4–11.5) and 12.5 months (95% CI, 3.7–21.3), respectively. Grade 3–4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3–4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred. Conclusion Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer. Trial registration ClinicalTrials.gov: NCT05025033, 27/08/2021.https://doi.org/10.1186/s12885-023-10661-4Immune checkpoint inhibitorsMolecular targeted therapySintilimabApatinibGastric cancer |
| spellingShingle | Le Zhang Weixue Wang Shaohua Ge Hongli Li Ming Bai Jingjing Duan Yuchong Yang Tao Ning Rui Liu Xia Wang Zhi Ji Feixue Wang Haiyang Zhang Yi Ba Ting Deng Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial BMC Cancer Immune checkpoint inhibitors Molecular targeted therapy Sintilimab Apatinib Gastric cancer |
| title | Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial |
| title_full | Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial |
| title_fullStr | Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial |
| title_full_unstemmed | Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial |
| title_short | Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial |
| title_sort | sintilimab plus apatinib and chemotherapy as second third line treatment for advanced gastric or gastroesophageal junction adenocarcinoma a prospective single arm phase ii trial |
| topic | Immune checkpoint inhibitors Molecular targeted therapy Sintilimab Apatinib Gastric cancer |
| url | https://doi.org/10.1186/s12885-023-10661-4 |
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