Adjuvant Subcutaneous Trastuzumab for HER2-Positive Early Breast Cancer: Subgroup Analyses of Safety and Active Medical Conditions by Body Weight in the SafeHer Phase III Study

Abstract

Background: This SafeHer subgroup analysis assessed the safety of fixed-dose subcutaneous trastuzumab (H SC) as an adjuvant therapy in HER2-positive early breast cancer (EBC) by body weight.

Patients and methods: Patients with HER2-positive EBC not previously treated with anti-HER2 therapy received H SC 600 mg (every 3 weeks for 18 cycles), with neoadjuvant or adjuvant chemotherapy or without adjuvant chemotherapy. Adverse events (AEs) were assessed throughout treatment and at final follow-up (28 ±5 days after last treatment). Subgroups were categorized by body weight, Asian origin, and chemotherapy administration. All analyses were descriptive.

Results: Of 2,577 patients enrolled, 2,573 received ≥1 dose of study medication and were included in this safety analysis. Median body weight at baseline was 67.0 kg (range 33.6-150.0 kg). Any-grade AEs occurred in 88.7% (2,282/2,573) of the overall population, versus 87.1% (590/677) of the lowest bodyweight quartile (≤59 kg), 90.0% (561/623) of the highest quartile (>77 kg), and 86.5% (327/378) of the Asian population. Grade ≥3 AEs occurred in 23.2% (596/2,573) of the overall population, 17.9% (121/677) of the lowest bodyweight quartile, 26.8% (167/623) of the highest quartile, and 15.3% (58/378) of the Asian population. The highest bodyweight quartile had the highest incidence of medical conditions at baseline (highest quartile, 75.6%; lowest quartile, 56.1%).

Conclusion: These data support the use of fixed-dose H SC as an adjuvant therapy in HER2-positive EBC and confirm the comparable safety profile of H SC in patients with low body weight or of Asian origin versus the overall population in SafeHer. ClinicalTrials.gov: NCT01566721.

Implications for practice: The safety profile of fixed-dose subcutaneous trastuzumab (H SC) was comparable between patients in the lowest bodyweight subgroup and the overall patient population, and also between patients of Asian origin (of whom a higher proportion often fall within the lower bodyweight quartiles) and the overall population. The safety data from this SafeHer subgroup analysis therefore support the use of fixed-dose H SC 600 mg administered every 3 weeks as an adjuvant therapy for patients with HER2-positive early breast cancer across different bodyweight subgroups and in the Asian patient population.

Keywords: Asian population; Body weight; Breast cancer; Human epidermal growth factor receptor 2‐positive; Subcutaneous injections; Trastuzumab.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

© AlphaMed Press 2018.

Figures

Figure 1.

Adverse events of interest by body weight and chemotherapy subgroups. System organ class categories of adverse events of interest were determined and agreed upon by the authors. Abbreviations: AE, adverse event; CHF, congestive heart failure.

Figure 2.

Grade ≥3 adverse events of interest by body weight and chemotherapy subgroups. System organ class categories of adverse events of interest were determined and agreed by the authors. Adverse events graded per National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0 [10]. Abbreviations: AE, adverse event; CHF, congestive heart failure.

Figure 3.

Serious adverse events of interest by body weight and chemotherapy subgroups. System organ class categories of adverse events of interest were determined and agreed by the authors. Abbreviations: CHF, congestive heart failure; SAE, serious adverse event.

Figure 4.

Active medical conditions at baseline by body weight and chemotherapy subgroups. The two most common individual diagnoses overall are listed for each system organ class.