The subgroup analysis by age and geriatric assessment in a phase III study comparison of trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in older patients with advanced stage HER2-positive breast cancer (JCOG1607 HERB TEA study).

person Akihiko Shimomura National Center for Global Health and Medicine, Tokyo, Japan info_outline Akihiko Shimomura, Kenji Tamura, Keita Sasaki, Ryo Sadachi, Akihiko Suto, Masataka Sawaki, Yasuaki Sagara, Naohito Yamamoto, Tomoyuki Yoshiyama, Takako Hayashi, Eriko Tokunaga, Takashi Yamanaka, Chikako Shimizu, Tadahiko Shien, Hiroji Iwata

Authors person Akihiko Shimomura National Center for Global Health and Medicine, Tokyo, Japan info_outline Akihiko Shimomura, Kenji Tamura, Keita Sasaki, Ryo Sadachi, Akihiko Suto, Masataka Sawaki, Yasuaki Sagara, Naohito Yamamoto, Tomoyuki Yoshiyama, Takako Hayashi, Eriko Tokunaga, Takashi Yamanaka, Chikako Shimizu, Tadahiko Shien, Hiroji Iwata Organizations National Center for Global Health and Medicine, Tokyo, Japan, Shimane University Hospital, Izumi-Shi, Shimane, Japan, Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan, Clinical Research Support Office, National Cancer Center Hospital, Tokyo, Japan, National Cancer Center Hospital, Chuo-Ku, Japan, Aichi Cancer Center Hospital, Nagoya-Shi Chikusa-Ku, Japan, Hakuaikai Medical Corp. Sagara HP, Kagoshima-Shi, Japan, Chiba Cancer Center, Chiba, Japan, Department of Medical Oncology & Breast Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan, NHO Nagoya Medical Center, Aichi, Japan, NHO Kyushu Cancer Center, Fukuoka, Japan, Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan, Okayama University Hospital, Okayama-Shi, Japan, Aichi Cancer Center Hospital, Nagoya, Japan Abstract Disclosures Research Funding Japan Agency for Medical Research and Development Background: The JCOG1607, HERB TEA Study, is a phase III trial that compared trastuzumab emtansine (T-DM1) with the HPD regimen (trastuzumab, pertuzumab, docetaxel) in older patients with advanced HER2-positive breast cancer. The primary objective was to confirm the non-inferiority of T-DM1 to HPD in overall survival (OS), with a margin of 1.35 for hazard ratio (HR). The trial was terminated early due to futility at the planned first interim analysis. T-DM1 didn't show non-inferiority to HPD in OS (HR 1.263; 95% confidence interval [CI], 0.677-2.357). Median progression-free survival (PFS) was 11.3 months for T-DM1 and 15.6 months for HPD (HR 1.373; 95% CI, 0.917-2.056). However, the condition of older patients varies widely, and we conducted a subgroup analysis to investigate the subgroup that could benefit from T-DM1 with fewer side effects as a first-line treatment. Methods: Subgroup analysis for OS and PFS involved 148 patients enrolled in JCOG1607, considering age and PS (<75 years old and PS 0,1 or <75 years old and PS 2 or ≥75 years old), Geriatric 8 (G8) score (≥15 or <15), Instrumental Activity of Daily Living (IADL) score (8 or <8), visceral/brain metastasis presence (with or without), and other factors. Results: Subgroup of <75 and PS 2 was not evaluable. For OS, HR of T-DM1 arm to HPD arm was 0.749 (95% CI: 0.310-1.808) in the group aged <75 years, while 2.867 (95%CI: 1.018-8.069) in the group aged ≥75 years (Table). G8 score and the IADL score did not show significant differences in HR for OS, although low G8 score group and low IADL score group tended to have higher OS in HPD arm than T-DM1 arm: HR of T-DM1 arm to HPD arm of 1.541 (95% CI: 0.755-3.142) in low G8 score group and 2.147 (95% CI: 0.656-7.025) in low IADL score group. For PFS, patients with visceral/brain metastasis had HR of T-DM1 arm to HPD arm of 1.794 (95% CI: 1.092-2.948). No other subgroup showed a significant difference in HR for PFS. Conclusions: No subgroups benefiting from T-DM1 as first-line treatment were identified. HPD remains the standard for advanced HER2-positive breast cancer, regardless of age (even in ≥75 years) G8 score, or IADL. Clinical trial information: UMIN000030783. Subgroup OS HR (95% CI) OS p-value PFS HR (95% CI) PFS p-value Age <75 years 0.749 (0.310-1.808) 0.5198 1.418 (0.843-2.383) 0.1877 Age ≥75 years 2.867 (1.018-8.069) 0.0461 1.367 (0.702-2.661) 0.3577 G8 score ≥15 0.990 (0.266-3.686) 0.9875 1.730 (0.864-3.464) 0.1221 G8 score <15 1.541 (0.755-3.142) 0.2347 1.297 (0.776-2.166) 0.3207 IADL score of 8 1.002 (0.470-2.135) 0.9957 1.286 (0.800-2.067) 0.2987 IADL score <8 2.147 (0.656-7.025) 0.2064 1.869 (0.854-4.092) 0.1178 With visceral/brain metastasis 1.504 (0.734-3.082) 0.2646 1.794 (1.092-2.948) 0.0211 Without visceral/brain metastasis 0.719 (0.191-2.700) 0.6251 0.864 (0.420-1.778) 0.6914