Favorable Toxicity Management with Sacituzumab Govitecan in Advanced Breast Cancer

CASE

• A 62-year-old woman presented with a 6 cm right breast mass, which has been slowly growing for 1 year with palpable axillary nodes​
• Liver function tests: Within normal limits
• CT scan showed 2 liver nodules; the largest is 2 cm​.
• Bone scan: extensive disease in thoracic spine, ribs​.
• Breast biopsy: grade 2 invasive ductal carcinoma; estrogen receptor positive, progesterone receptor positive, HER2 immunohistochemistry (IHC) was 0, BRCA1/2 negative​.
• Liver biopsy confirms metastatic disease with similar markers​.
• Stage T3N1M1 ​
• ECOG performance status: 0 ​
• Treatment with letrozole plus ribociclib (Kisqali) was initiated​.
• Bisphosphonate was given to address bone metastasis.
• Circulating tumor DNA was collected and sent for genomic testing. It did not show PIK3CA, ESR1, or other actionable mutations.
• Patient progressed after endocrine and CDK4/6 inhibitor therapy. She received fulvestrant plus everolimus for progressive disease. ​
• Initial follow-up imaging post-treatment showed stable disease. Six months post-treatment, imaging showed liver and lung nodules enlarged from initial post-treatment scan.​
• The patient was treated with capecitabine until progression of disease.

Targeted Oncology: Based on the TROPiCS-02 trial (NCT03901339), how does a patient’s HER2 immunohistochemistry status impact results with sacituzumab govitecan (Trodelvy)?

ADITYA BARDIA, MD, MPH: In terms of HER2 [expression]…the drug targets Trop-2, so we would expect that the HER2 results would not matter and that's what was seen [on this trial].¹ For patients with a HER2 low tumor or an IHC HER 2 score of 0, the [efficacy] benefit was maintained with sacituzumab govitecan. Overall, in terms of the response rate, it was higher with sacituzumab govitecan compared with standard therapy, [at 21% vs 14%, respectively (HR 1.66; 95% CI, 1.06-2.61), P = .027)].¹

What was the toxicity profile seen with this therapy?

Aditya Bardia, MD, MPH​

Director, Breast Cancer Research Program

Massachusetts General Hospital, Harvard Medical School​

Boston, MA​

The drug has SN-38, so the adverse event [AE] profile would be similar to what you would see with irinotecan [with] myelosuppression, nausea, diarrhea, and alopecia.¹ It's the incidence of certain AEs [with sacituzumab govitecan] that are lower compared with irinotecan. [For example], grade 3 diarrhea with irinotecan is about 30%, but with [sacituzumab govitecan] it's 10%.

The advantage of the antibody-drug conjugate [ADC] is that you get more delivery of the payload to tumor cells, so there is a better efficacy and conceptually lower toxicity. [However,] it still does have myelosuppression events, and patients sometimes need granulocyte colony-stimulating [G-CSF] as secondary prophylaxis.¹ For nausea, I usually use a 3-drug antiemetic regimen to start with, and then [to help them deal with] diarrhea I usually give patients a prescription of imodium.

What infusion-related reactions, if any, occur with this drug?

Allergic reactions, or infusion related reactions, to sacituzumab govitecan have been described, but they're not very common.¹ It's like with any other antibody, where any-grade anaphylactic reactions are quite rare.² I personally have had a couple of patients with anaphylactic reactions to sacituzumab govitecan, but it's certainly not very common, yet something that can be seen [in patients].

What role does G-CSF play in treating patients who develop neutropenia with this therapy?

In general, I don't use primary prophylaxis with G-CSF, but I do consider secondary prophylaxis with G-CSF if a patient is having a prolonged neutropenia. Rarely, I would consider primary prophylaxis with G-CSF in a patient who is elderly that you're worried that if has neutropenic fever that could be very serious, or the baseline counts are low, but in general, it's more a secondary prophylaxis. Then, it depends whether you want to use short-acting or long-acting G-CSF depending on what you're trying to address [for the patient]. If you want to correct the day 8 neutropenia with sacituzumab govitecan, then use short-acting G-CSF a few days before that, so around day 4 or 5. If you're trying to address it on day 1 of cycle 2 or cycle 3, then with the previous cycle you can use a long-acting G-CSF on day 8, because that will help the next cycle.

^References

^{1. Tolaney S, Bardia A, Marme 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(16):1003-1003. doi:10.1200/JCO.2023.41.16_suppl.1003}

^{2. D'Arienzo A, Verrazzo A, Pagliuca M, et al. Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations. EClinicalMedicine. 2023;62:102113. doi:10.1016/j.eclinm.2023.102113}