Masataka Sawaki1, Naruto Taira2, Yukari Uemura3, Tsuyoshi Saito4, Shinichi Baba5, Kokoro Kobayashi6, Hiroaki Kawashima7, Michiko Tsuneizumi8, Noriko Sagawa9, Hiroko Bando10, Masato Takahashi11, Miki Yamaguchi12, Tsutomu Takashima13, Takahiro Nakayama14, Masahiro Kashiwaba5, Toshiro Mizuno15, Yutaka Yamamoto16, Hiroji Iwata1, Takuya Kawahara17, Yasuo Ohashi18, Hirofumi Mukai19. 1. Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 2. Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan. 3. Biostatistics Section, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan. 4. Department of Surgery, Japanese Red Cross Saitama Hospital, Saitama, Japan. 5. Department of Surgery, Sagara Hospital, Kagoshima, Japan. 6. Department of Medical Oncology, the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. 7. Department of Surgery, Aomori City Hospital, Aomori, Japan. 8. Department of Breast Surgery, Shizuoka General Hospital, Shizuoka, Japan. 9. Department of Breast Surgery, Kameda Medical Center, Kamogawa, Japan. 10. Department of Breast and Endocrine Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 11. Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan. 12. Department of Breast Surgery, JCHO Kurume General Hospital, Kurume, Japan. 13. Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 14. Department of Breast and Endocrine Surgery, Osaka International Cancer Institute, Osaka Japan. 15. Department of Medical Oncology, Mie University Hospital, Tsu, Japan. 16. Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 17. Biostatistics Division, Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan. 18. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan. 19. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Abstract
PURPOSE: Adjuvant trastuzumab monotherapy has not been compared with trastuzumab + chemotherapy. We investigated the relative value of trastuzumab monotherapy for older patients with breast cancer. METHODS: This study was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients aged 70-80 years with surgically treated human epidermal growth factor receptor 2-positive invasive breast cancer receivedtrastuzumab monotherapy or trastuzumab + chemotherapy. The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR), relapse-free survival (RFS), adverse events (AEs), health-related quality of life (HRQoL), and restricted mean survival time (RMST). RESULTS: The study involved 275 patients (mean age, 73.5 years) who were followed up for a mean of 4.1 years (range, 0.3-8.0 years). The percentages of patients by cancer stage were as follows: I (pT > 0.5 cm), 43.6%; IIA, 41.7%; IIB, 13.5%; and IIIA, 1.1%. Three-year DFS was 89.5% with trastuzumab monotherapy versus 93.8% with trastuzumab + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; P = .51). At 3 years, RMST differed by -0.39 months between arms (95% CI, -1.71 to 0.93; P = .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab + chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79; P = .53). Common AEs were anorexia (7.4% v 44.3%; P < .0001) and alopecia (2.2% v 71.7%; P < .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% (P = .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy v 48% for trastuzumab + chemotherapy; P = .016) and at 1 year (19% v 38%; P = .009). CONCLUSION: The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was < 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.
RCT Entities:
PURPOSE: Adjuvant trastuzumab monotherapy has not been compared with trastuzumab + chemotherapy. We investigated the relative value of trastuzumab monotherapy for older patients with breast cancer. METHODS: This study was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients aged 70-80 years with surgically treated humanepidermal growth factor receptor 2-positive invasive breast cancer received trastuzumab monotherapy or trastuzumab + chemotherapy. The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR), relapse-free survival (RFS), adverse events (AEs), health-related quality of life (HRQoL), and restricted mean survival time (RMST). RESULTS: The study involved 275 patients (mean age, 73.5 years) who were followed up for a mean of 4.1 years (range, 0.3-8.0 years). The percentages of patients by cancer stage were as follows: I (pT > 0.5 cm), 43.6%; IIA, 41.7%; IIB, 13.5%; and IIIA, 1.1%. Three-year DFS was 89.5% with trastuzumab monotherapy versus 93.8% with trastuzumab + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; P = .51). At 3 years, RMST differed by -0.39 months between arms (95% CI, -1.71 to 0.93; P = .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab + chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79; P = .53). Common AEs were anorexia (7.4% v 44.3%; P < .0001) and alopecia (2.2% v 71.7%; P < .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% (P = .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy v 48% for trastuzumab + chemotherapy; P = .016) and at 1 year (19% v 38%; P = .009). CONCLUSION: The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was < 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.