The Importance of Full-Dose Sacituzumab Govitecan-hziy

Sacituzumab govitecan-hziy is indicated for patients with metastatic triple-negative breast cancer (mTNBC) following ≥2 prior therapies, with ≥1 for metastatic disease, at a dose of 10 mg/kg intravenously on days 1 and 8, cycled every 21 days.^1,2 Results from a phase 1 dose-escalation study of sacituzumab govitecan-hziy in diverse metastatic cancer patients showed that doses >10 mg/kg were not well-tolerated or delays within or between cycles were necessary.³ The subsequent phase 2 expansion study found that the 8-mg/kg and 10-mg/kg doses had similar adverse event (AE) profiles, but the 10-mg/kg dose had significantly superior efficacy in patients with mTNBC.³

The clinical benefit rate was defined as the percentage of patients who reached confirmed complete and partial responses to treatment with sacituzumab govitecan-hziy. It also included those who achieved stable disease for ≥6 months (in those with TNBC).³ The data show that, for patients with mTNBC, the objective response rate and clinical benefit rate in the 10-mg/kg dose were double those of the 8-mg/kg dose, showing a significant improvement in efficacy.

The initial phase 1 dose-escalation study showed that sacituzumab govitecan-hziy has a stable pharmacokinetic profile and tolerable toxicity at doses of 8 mg/kg and 10 mg/kg. According to the study results, the efficacy data show significantly better efficacy results at 10 mg/kg compared with the 8-mg/kg dose, for mTNBC, and similar rates of AEs between the 8-mg/kg and 10-mg/kg doses, although slightly more grade ≥3 events occurred in the 10-mg/kg group.

The superior efficacy versus slightly worse AE profile is the reasoning for the approved dosage of 10 mg/kg. It is important to correctly calculate the dosage for intravenous infusion based on the patient’s body weight and important to check the patient’s weight at subsequent treatments for any significant weight changes.³ A lower than advised starting dose could result in drastically reduced efficacy with a similar AE profile. Educating your patients on the risk-benefit ratio of the 10-mg/kg dose is of utmost importance, with AEs managed symptomatically as they arise or by premedicating patients, to ensure the optimal efficacious dose of sacituzumab govitecan-hziy is provided.

References

1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer. Version 8.2021. Updated September 13, 2021. www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed December 1, 2021.
2. Trodelvy (sacituzumab govitecan-hziy) dosing, reconstitution and administration guide. www.trodelvyhcp.com/-/media/project/trodelvy/trodelvyhcp/files/dosing-reconstitution-admin-booklet.pdf. Accessed November 28, 2021.
3. Ocean AJ, Starodub AN, Bardia A, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: safety and pharmacokinetics. Cancer. 2017;123:3843-3854.