Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial
Abstract Background The JACOB trial (NCT01774786) was a double-blinded, placebo-controlled, randomized, multicenter, international, phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemotherapy in first-line treatment of human epidermal growth factor recepto...
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| Format: | Article |
| Language: | English |
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Wiley
2019-06-01
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| Series: | Cancer Communications |
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| Online Access: | http://link.springer.com/article/10.1186/s40880-019-0384-6 |
| _version_ | 1819203658699505664 |
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| author | Tianshu Liu Yanru Qin Jin Li Ruihua Xu Jianming Xu Shujun Yang Shukui Qin Yuxian Bai Changping Wu Yixiang Mao Haiyan Wu Yilin Ge Lin Shen |
| author_facet | Tianshu Liu Yanru Qin Jin Li Ruihua Xu Jianming Xu Shujun Yang Shukui Qin Yuxian Bai Changping Wu Yixiang Mao Haiyan Wu Yilin Ge Lin Shen |
| author_sort | Tianshu Liu |
| collection | DOAJ |
| description | Abstract Background The JACOB trial (NCT01774786) was a double-blinded, placebo-controlled, randomized, multicenter, international, phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemotherapy in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer (GEJC). The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial. Methods This post hoc subpopulation analysis included all patients recruited in mainland China (n = 163; 20.9%) between June 2013 and January 2016. The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy (pertuzumab group; n = 82) or placebo plus trastuzumab and chemotherapy (control group; n = 81). Intravenous pertuzumab (840 mg) and trastuzumab (8 mg/kg loading and 6 mg/kg maintenance doses) were given every 3 weeks until disease progression or unacceptable toxicity. Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin. The primary endpoint was overall survival (OS); secondary efficacy endpoints included progression-free survival (PFS), and overall objective response rate (ORR). Results The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.49 to 1.14). The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups, respectively (HR 0.85; 95% CI 0.60 to 1.21), and the median ORRs were 68.9% and 55.7%, respectively. The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group. The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable. The most common grade 3–5 adverse events were neutropenia, anemia, and leukopenia. However, due to the nature of being a post hoc subgroup analysis, the results presented here are descriptive only and need to be interpreted with caution. Conclusions OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients, and this regimen demonstrated an acceptable safety profile. Trial registration ClinicalTrials.gov. NCT01774786. Registered on 24 January 2013, https://clinicaltrials.gov/ct2/show/NCT01774786 |
| first_indexed | 2024-12-23T04:23:25Z |
| format | Article |
| id | doaj.art-14baf00219d243e98452f134e1b88c54 |
| institution | Directory Open Access Journal |
| issn | 2523-3548 |
| language | English |
| last_indexed | 2024-12-23T04:23:25Z |
| publishDate | 2019-06-01 |
| publisher | Wiley |
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| series | Cancer Communications |
| spelling | doaj.art-14baf00219d243e98452f134e1b88c542022-12-21T18:00:11ZengWileyCancer Communications2523-35482019-06-0139111010.1186/s40880-019-0384-6Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trialTianshu Liu0Yanru Qin1Jin Li2Ruihua Xu3Jianming Xu4Shujun Yang5Shukui Qin6Yuxian Bai7Changping Wu8Yixiang Mao9Haiyan Wu10Yilin Ge11Lin Shen12Department of Oncology, Zhongshan Hospital, Fudan UniversityDepartment of Clinical Oncology, The First Affiliated Hospital, Zhengzhou UniversityDepartment of Medical Oncology, Fudan University Shanghai Cancer CenterDepartment of Medical Oncology, Sun Yat-Sen University Cancer CenterDepartment of Oncology, 307th Hospital of PLA, Academy of Military Medical SciencesDepartment of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer HospitalDepartment of Oncology, People’s Liberation Army (PLA) Cancer Center, 81st Hospital of PLAMedical Department, Harbin Medical University Cancer HospitalDepartment of Oncology, First People’s Hospital of ChangzhouRoche (China) Holding Co., Ltd.Roche (China) Holding Co., Ltd.Medical Division, Shanghai Roche Pharmaceuticals Ltd.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and InstituteAbstract Background The JACOB trial (NCT01774786) was a double-blinded, placebo-controlled, randomized, multicenter, international, phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemotherapy in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer (GEJC). The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial. Methods This post hoc subpopulation analysis included all patients recruited in mainland China (n = 163; 20.9%) between June 2013 and January 2016. The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy (pertuzumab group; n = 82) or placebo plus trastuzumab and chemotherapy (control group; n = 81). Intravenous pertuzumab (840 mg) and trastuzumab (8 mg/kg loading and 6 mg/kg maintenance doses) were given every 3 weeks until disease progression or unacceptable toxicity. Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin. The primary endpoint was overall survival (OS); secondary efficacy endpoints included progression-free survival (PFS), and overall objective response rate (ORR). Results The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.49 to 1.14). The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups, respectively (HR 0.85; 95% CI 0.60 to 1.21), and the median ORRs were 68.9% and 55.7%, respectively. The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group. The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable. The most common grade 3–5 adverse events were neutropenia, anemia, and leukopenia. However, due to the nature of being a post hoc subgroup analysis, the results presented here are descriptive only and need to be interpreted with caution. Conclusions OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients, and this regimen demonstrated an acceptable safety profile. Trial registration ClinicalTrials.gov. NCT01774786. Registered on 24 January 2013, https://clinicaltrials.gov/ct2/show/NCT01774786http://link.springer.com/article/10.1186/s40880-019-0384-6Gastric cancerGastroesophageal junction cancerHER2PertuzumabTrastuzumabChemotherapy |
| spellingShingle | Tianshu Liu Yanru Qin Jin Li Ruihua Xu Jianming Xu Shujun Yang Shukui Qin Yuxian Bai Changping Wu Yixiang Mao Haiyan Wu Yilin Ge Lin Shen Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial Cancer Communications Gastric cancer Gastroesophageal junction cancer HER2 Pertuzumab Trastuzumab Chemotherapy |
| title | Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial |
| title_full | Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial |
| title_fullStr | Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial |
| title_full_unstemmed | Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial |
| title_short | Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial |
| title_sort | pertuzumab in combination with trastuzumab and chemotherapy for chinese patients with her2 positive metastatic gastric or gastroesophageal junction cancer a subpopulation analysis of the jacob trial |
| topic | Gastric cancer Gastroesophageal junction cancer HER2 Pertuzumab Trastuzumab Chemotherapy |
| url | http://link.springer.com/article/10.1186/s40880-019-0384-6 |
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