Akitaka Makiyama1, Yasutaka Sukawa2, Tomomi Kashiwada3, Junji Kawada4, Ayumu Hosokawa5, Yoshiki Horie6, Akihito Tsuji7, Toshikazu Moriwaki8, Hiroaki Tanioka9, Katsunori Shinozaki10, Keita Uchino11, Hirofumi Yasui12, Hiroshi Tsukuda13, Kazuhiro Nishikawa14, Hiroyasu Ishida15, Takeharu Yamanaka16, Kentaro Yamazaki17, Shuichi Hironaka18, Taito Esaki19, Narikazu Boku20, Ichinosuke Hyodo8, Kei Muro21. 1. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka; and Cancer Center, Gifu University Hospital, Gifu, Japan. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. 3. Department of Hematology/Oncology, Saga University Hospital, Saga, Japan. 4. Department of Surgery, Kaizuka City Hospital, Osaka, Japan. 5. Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, Toyama, Japan. 6. Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan. 7. Department of Clinical Oncology, Kagawa University Faculty of Medicine, Kita-gun, Japan. 8. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 9. Department of Clinical Oncology, Kawasaki Medical School, Okayama, Japan. 10. Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan. 11. Department of Medical Oncology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 12. Department of GI Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 13. Department of Oncology, Izumi City General Hospital, Osaka, Japan. 14. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. 15. Department of Gastroenterology, National Health Organization, Mito Medical Center, Ibaraki, Japan. 16. Department of Biostatistics, Yokohama City University, Yokohama, Japan. 17. Clinical Trial Coordination Unit and Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 18. Division of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan. 19. Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 20. Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 21. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Abstract
PURPOSE: This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS: Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination withfluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed. RESULTS: Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively (P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found. CONCLUSION: The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.
RCT Entities:
PURPOSE: This study evaluated the continuous use of trastuzumab beyond progression (TBP) in humanepidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS: Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed. RESULTS: Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively (P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found. CONCLUSION: The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.
Authors: Jeremy Chuang; Samuel Klempner; Kevin Waters; Katelyn Atkins; Joseph Chao; May Cho; Andrew Hendifar; Alexandra Gangi; Miguel Burch; Pareen Mehta; Jun Gong Journal: Diseases Date: 2022-04-19
Authors: Nicole M Myer; Kohei Shitara; Hyun C Chung; Florian Lordick; Ronan J Kelly; Zsolt Szabo; Z Alexander Cao; Stephen Leong; David H Ilson; Wilko Weichert Journal: J Cancer Res Clin Oncol Date: 2022-05-13 Impact factor: 4.322
Authors: Daniel V T Catenacci; Stephanie Moya; Samantha Lomnicki; Leah M Chase; Bryan F Peterson; Natalie Reizine; Lindsay Alpert; Namrata Setia; Shu-Yuan Xiao; John Hart; Uzma D Siddiqui; D Kyle Hogarth; Oliver S Eng; Kiran Turaga; Kevin Roggin; Mitchell C Posner; Paul Chang; Sunil Narula; Murtuza Rampurwala; Yuan Ji; Theodore Karrison; Chih-Yi Liao; Blase N Polite; Hedy L Kindler Journal: Cancer Discov Date: 2020-11-24 Impact factor: 39.397