Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial
Abstract Background We evaluated the antitumor activity and safety of avelumab, a human anti–PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy. Methods...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2019-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40425-019-0508-1 |
| _version_ | 1818487442178572288 |
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| author | Hyun Cheol Chung Hendrik-Tobias Arkenau Jeeyun Lee Sun Young Rha Do-Youn Oh Lucjan Wyrwicz Yoon-Koo Kang Keun-Wook Lee Jeffrey R. Infante Sung Sook Lee Margaret Kemeny Ulrich Keilholz Bohuslav Melichar Alain Mita Ruth Plummer Denis Smith Arnold B. Gelb Huiling Xiong Janet Hong Vikram Chand Howard Safran |
| author_facet | Hyun Cheol Chung Hendrik-Tobias Arkenau Jeeyun Lee Sun Young Rha Do-Youn Oh Lucjan Wyrwicz Yoon-Koo Kang Keun-Wook Lee Jeffrey R. Infante Sung Sook Lee Margaret Kemeny Ulrich Keilholz Bohuslav Melichar Alain Mita Ruth Plummer Denis Smith Arnold B. Gelb Huiling Xiong Janet Hong Vikram Chand Howard Safran |
| author_sort | Hyun Cheol Chung |
| collection | DOAJ |
| description | Abstract Background We evaluated the antitumor activity and safety of avelumab, a human anti–PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy. Methods In a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety. Results Overall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5–13.9% and 1.8–16.2%, respectively), including complete responses in 2.2% of the 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0–not estimable) and 3.5 months (95% CI, 2.8–8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3–4.1) and 1.4 months (95% CI, 1.3–1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7–32.4%) and 7.9% (95% CI, 2.6–17.2%), and median OS was 11.1 months (95% CI, 8.9–13.7) and 6.6 months (95% CI, 5.4–9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (95% CI, 15.4–20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade ≥3 TRAE, including 1 treatment-related death. Conclusion Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC. Trial registration ClinicalTrials.gov NCT01772004; registered 21 January 2013. |
| first_indexed | 2024-12-10T16:37:41Z |
| format | Article |
| id | doaj.art-22a26bd6feb14e4185d7a995dfe688b6 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-12-10T16:37:41Z |
| publishDate | 2019-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-22a26bd6feb14e4185d7a995dfe688b62022-12-22T01:41:21ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262019-02-017111010.1186/s40425-019-0508-1Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trialHyun Cheol Chung0Hendrik-Tobias Arkenau1Jeeyun Lee2Sun Young Rha3Do-Youn Oh4Lucjan Wyrwicz5Yoon-Koo Kang6Keun-Wook Lee7Jeffrey R. Infante8Sung Sook Lee9Margaret Kemeny10Ulrich Keilholz11Bohuslav Melichar12Alain Mita13Ruth Plummer14Denis Smith15Arnold B. Gelb16Huiling Xiong17Janet Hong18Vikram Chand19Howard Safran20Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health SystemSarah Cannon Research Institute/University College LondonSamsung Medical Center, Sungkyunkwan University School of MedicineYonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health SystemSeoul National University Hospital, Cancer Research Institute, Seoul National University College of MedicineCentrum Onkologii-Instytut im. M. Sklodowskiej CurieAsan Medical Center, University of Ulsan College of MedicineSeoul National University Bundang Hospital, Seoul National University College of MedicineSarah Cannon Research Institute/Tennessee Oncology, PLLCInje University College of MedicineQueens Cancer Center, Mt Sinai School of MedicineCharité Comprehensive Cancer CenterPalacky University Medical School and Teaching HospitalSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterNorthern Centre for Cancer Care and Newcastle University, Freeman HospitalMedical Oncology, Bordeaux University HospitalEMD Serono, IncEMD Serono, IncEMD Serono, IncEMD Serono, IncBrown UniversityAbstract Background We evaluated the antitumor activity and safety of avelumab, a human anti–PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy. Methods In a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety. Results Overall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5–13.9% and 1.8–16.2%, respectively), including complete responses in 2.2% of the 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0–not estimable) and 3.5 months (95% CI, 2.8–8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3–4.1) and 1.4 months (95% CI, 1.3–1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7–32.4%) and 7.9% (95% CI, 2.6–17.2%), and median OS was 11.1 months (95% CI, 8.9–13.7) and 6.6 months (95% CI, 5.4–9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (95% CI, 15.4–20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade ≥3 TRAE, including 1 treatment-related death. Conclusion Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC. Trial registration ClinicalTrials.gov NCT01772004; registered 21 January 2013.http://link.springer.com/article/10.1186/s40425-019-0508-1AvelumabMetastaticGastricEsophagogastric junctionAdenocarcinomaMaintenance |
| spellingShingle | Hyun Cheol Chung Hendrik-Tobias Arkenau Jeeyun Lee Sun Young Rha Do-Youn Oh Lucjan Wyrwicz Yoon-Koo Kang Keun-Wook Lee Jeffrey R. Infante Sung Sook Lee Margaret Kemeny Ulrich Keilholz Bohuslav Melichar Alain Mita Ruth Plummer Denis Smith Arnold B. Gelb Huiling Xiong Janet Hong Vikram Chand Howard Safran Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial Journal for ImmunoTherapy of Cancer Avelumab Metastatic Gastric Esophagogastric junction Adenocarcinoma Maintenance |
| title | Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial |
| title_full | Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial |
| title_fullStr | Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial |
| title_full_unstemmed | Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial |
| title_short | Avelumab (anti–PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial |
| title_sort | avelumab anti pd l1 as first line switch maintenance or second line therapy in patients with advanced gastric or gastroesophageal junction cancer phase 1b results from the javelin solid tumor trial |
| topic | Avelumab Metastatic Gastric Esophagogastric junction Adenocarcinoma Maintenance |
| url | http://link.springer.com/article/10.1186/s40425-019-0508-1 |
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