Subcutaneous Trastuzumab and Hyaluronidase-oysk with IV Pertuzumab/Docetaxel in HER2+ Advanced Breast Cancer: Final Analysis of the MetaPHER Study

In the HannaH and SafeHER studies, fixed-dose subcutaneous (SC) trastuzumab and hyaluronidase-oysk (Herceptin Hylecta™; H SC) has been shown to be noninferior to weight-based intravenous (IV) trastuzumab (Herceptin^®; H IV) in terms of pathologic complete response and serum trough concentration in HER2+ early breast cancer, with a comparable safety profile, and demonstrated a compelling patient preference for H SC.^1-4 IV pertuzumab (Perjeta®; P IV) plus H IV plus docetaxel (D IV) was also shown to significantly improve progression-free survival (PFS) and overall survival versus placebo plus H IV plus D IV in HER2+ metastatic breast cancer.^5,6 At SABCS 2019, the results from the final analysis of MetaPHER, the largest study to evaluate safety and tolerability of first-line H SC + P IV + D IV for HER2+ metastatic/locally advanced breast cancer, were reported.⁷

In this study, patients who had received no previous systemic nonhormonal anticancer therapy for their disease, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and a left ventricular ejection fraction (LVEF) ≥50% received 600 mg H SC + 840-mg loading/420-mg maintenance doses of P IV + ≥6 cycles of D IV (75 mg/m² → 100 mg/m²; >6 cycles were given at the investigator’s discretion) every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end. The primary objective was to evaluate safety and tolerability. Exploratory efficacy end points were PFS and objective response rate (ORR). A total of 412 patients were treated and analyzed for safety, and 160 remained on treatment at study end. Median follow-up was 27 months. Most patients experienced ≥1 any-grade adverse events (AEs; 406; 98.5%); 221 (53.6%) experienced grade ≥3 AEs; 107 (26.0%) experienced serious AEs; 87 (21.1%) experienced AEs leading to withdrawal from any study treatment; and 87 (21.1%) experienced investigator-reported administration-related and local injection-site reactions (21 [5.1%] H SC-related). There were 87 deaths (21.1%): 73 (17.7%) from disease progression, 9 (2.2%) due to AEs, and 5 (1.2%) due to other causes after treatment discontinuation. Three patients (0.7%) experienced grade ≥3 cardiac AEs, and 1 (0.2%) experienced a serious AE suggestive of congestive heart failure. Of the 396 patients with LVEF measurements at baseline and ≥1 postbaseline visits, 40 (10.1%) had LVEF drops (to <50% and ≥10% points from baseline; the majority were asymptomatic and did not lead to study drug discontinuation); only 2 patients (0.5%) had symptomatic left ventricular systolic dysfunction. There were no cardiac deaths.

The median investigator-assessed PFS was 18.7 months, with an ORR of 75.6%, and a clinical benefit rate of 92.0%. The authors concluded that the safety profile of first-line H SC + P IV + D IV for HER2+ advanced breast cancer was consistent with the known safety profile of H IV + P IV + D IV, with no new safety signals identified. Efficacy data were supportive of historical reports of H IV + P IV + D IV.

References

1. Jackisch C, et al. Eur J Cancer. 2016;62:62-75.
2. Jackisch C, et al. JAMA Oncol. 2019;5:e190339.
3. Gligorov J, et al. Eur J Cancer. 2017;82:237-246.
4. Jung KH, et al. Oncologist. 2018;23:1137-1143.
5. Kümmel S, et al. SABCS 2016. Abstract P4-21-42.
6. Kümmel S, et al. ESMO 2018. Abstract 323P.
7. Kummel S, et al. SABCS 2019. Abstract P1-18-05.