Exploring Sacituzumab Survival, Dosing in Advanced Breast Cancer

Megan Kruse, MD

Associate Staff, Hematology and Medical Oncology

Cleveland Clinic

Member, Developmental Therapeutics Program

Case Comprehensive Cancer Center

Cleveland, OH

This article is part 2 of a 2-part series from a Case-Based Roundtable event.

Targeted Oncology: What are your thoughts on the efficacy seen in the initial analysis of TROPiCS-02 (NCT03901339) for patients with later-line metastatic breast cancer?

Megan Kruse, MD: When this first came out, I was a little dubious, because sacituzumab govitecan [Trodelvy] improved median progression-free survival [PFS] by 1.5 months [stratified HR, 0.65; 95% CI, 0.53-0.81; P = .0001].¹ So it doesn't seem that great, but it's still an option, and we know that so many of our patients are still in need of therapy after those 4 or 5 prior lines from metastatic disease.

I think what changed a lot of people's opinion is shortly after we saw the results for this primary end point from TROPiCS-02, we saw the overall survival [OS] update. The final analysis came out about 5 months after the initial analysis was reported, but there was an OS benefit of about 3 months [with sacituzumab vs treatment of physicians’ choice (HR, 0.79; 95% CI, 0.65-0.96; P = .020)].² So it makes me stop and say, we don't see OS benefits that often and this is a very heavily pretreated group, so clearly, the drug is active in doing something. That leads into the enthusiasm to look at it in an earlier group of patients.

Sacituzumab works regardless of HER2 status…. HER2 biomarker is not a separate disease state.¹ It's a biomarker of response to a particular drug, so there's no reason to think that sacituzumab wouldn't work in these for patients with HER2-low disease, and indeed it does.

What are the options when it comes to dosing with sacituzumab?

There are 2 schools of thought. One is patients clearly do a lot better at a slightly lower dose or with more support if they can tolerate growth factor, so then they're getting more of their doses on time, and their relative dose intensity is higher. Or do you start at a lower dose and know that maybe they're not at dose level 1, but they're not missing doses unless their dose is higher? I don't think we know, and [there is discussion about] to up the dose on a slightly different schedule. So I think a lot to come about sacituzumab and how we use it and what the optimal doses are. But there's no doubt...from the published data that rates of serious treatment-related adverse events are higher with sacituzumab than with standard chemotherapy [28% vs 19%] and there are more dose delays [66% vs 44%].¹

What were the more common toxicities seen in TROPiCS-02?

If you look at those toxicities, it was neutropenia, diarrhea, and sometimes then constipation because you're responding to the diarrhea. I had a decent amount of anemia on this too, and I think the other patient-[reported] events—the alopecia is real, the fatigue is certainly real. When you look at standard chemotherapy, about the only thing that was worse because of the comparative drugs that were used were things like thrombocytopenia with gemcitabine, or neuropathy. I think neuropathy is one where sacituzumab can be favorable if you have someone who has a lot of treatment-related neuropathy.

How is sacituzumab being evaluated in earlier lines of treatment?

ASCENT-07 [NCT05840211] is a trial that accrued very quickly, particularly [outside of] the United States. Hopefully we will see [the results] later this year...maybe at the timeframe of the European Society for Medical Oncology Congress and San Antonio Breast Cancer Symposium. This is first-line use of sacituzumab. Think about this a little bit more like Destiny-BREAST06 [NCT04494425]. Of course you would have patients here without the biomarker; HER2 low is not going to matter. But essentially, after endocrine therapy, [patients are] going straight on to sacituzumab vs getting a taxane or capecitabine. I think this is eagerly anticipated, because then we're going to be able to answer the question of, is it more tolerable, and if we use it earlier, do patients do better? It's still going to leave us in this hole of doing trastuzumab deruxtecan [Enhertu] vs sacituzumab, but I think that's going to be our constant battle.

DISCLOSURES: Kruse previously reported honoraria from Curio Science; a consulting or advisory role for AstraZeneca/Daiichi Sankyo, GE Healthcare, Genentech, and Gilead Sciences; and research funding from AstraZeneca.

REFERENCES:

1. Tolaney SM, Bardia A, Marmé F, et al. Final overall survival (OS) analysis from the phase 3 TROPiCS-02 study of sacituzumab govitecan (SG) in patients (pts) with hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC). J Clin Oncol. 2023;41(suppl 16):1003. doi:10.1200/JCO.2023.41.16_suppl.1003

2. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023;402(10411):1423-1433. doi:10.1016/S0140-6736(23)01245-X