Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients.

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 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.

• Authors: Masataka Sawaki, Naruto Taira, Yukari Uemura, Tsuyoshi Saito, Shinichi Baba, Kokoro Kobayashi, Hiroaki Kawashima, Michiko Tsuneizumi, Noriko Sagawa, Hiroko Bando, Masato Takahashi, Miki Yamaguchi, Tsutomu Takashima, Takahiro Nakayama, Masahiro Kashiwaba, Toshiro Mizuno, Yutaka Yamamoto, Hiroji Iwata, Takuya Kawahara, Yasuo Ohashi, Hirofumi Mukai, RESPECT study group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 32 Pg. 3743-3752 (11 10 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 32936713 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Docetaxel
• Epirubicin
• Doxorubicin
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, enzymology, pathology)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Docetaxel (administration & dosage)
• Doxorubicin (administration & dosage)
• Epirubicin (administration & dosage)
• Female
• Humans
• Neoplasm Staging
• Quality of Life
• Receptor, ErbB-2 (metabolism)
• Survival Rate
• Trastuzumab (administration & dosage, therapeutic use)