Survival Outcomes with Sacituzumab Govitecan Increase in HR+ mBC

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 shows 2 liver nodules, the largest is 2 cm​.
• Bone scan: extensive disease in thoracic spine, ribs​.
• Breast biopsy: grade 2 IDC; estrogen receptor (ER) positive, progesterone receptor (PR) positive, HER2 immunohistochemistry 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. 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: What data would you look to in order to decide on a treatment for a patient like this with metastatic breast cancer (mBC)?

ADITYA BARDIA, MD, MPH​: The TROPiCS-02 trial [NCT03901339] looked at sacituzumab govitecan [Trodelvy], which is a Trop-2 directed antibody-drug conjugate [ADC].¹ This drug essentially has SN-38 the active metabolite of Irinotecan attached to the Trop-2 antibody, so the [toxicity] profile is like what we see with irinotecan.

Aditya Bardia, MD, MPH​

Director, Breast Cancer Research Program

Massachusetts General Hospital, Harvard Medical School​

Boston, MA​

The idea [behind this therapy] is that you can deliver much higher doses of SN-38 because of the ADC mechanism [rather] than just giving irinotecan. So, this trial evaluated [sacituzumab govitecan] in patients with HR-positive mBC who had endocrine-resistant disease. The patients on the trial were randomly assigned to sacituzumab govitecan or treatment of physician choice, between capecitabine, vinorelbine, gemcitabine, or eribulin.

What were the characteristics of patients on this trial and their results with the ADC?

In terms of baseline characteristics, they were well balanced between the 2 arms. A majority of patients had visceral metastases at 95% and a subset of patients had De novo metastatic disease, [with 29% in the sacituzumab govitecan arm and 22% in the physician choice arm].¹ All patients received prior therapy including CDK4/6 inhibitors; the trial required prior CDK4/6 inhibitor use. In terms of results, the study met its primary end point [and showed] there was improvement in patient's progression free-survival [PFS] with sacituzumab govitecan.¹

Initially, the results were modest with a median PFS of 5.5 months [95% CI, 4.2%-6.9%] with sacituzumab govitecan vs a median 4.0 months [95% CI, 3.0-4.4] with standard therapy [HR 0.65; 95% CI 0.53-0.81; P < .0001].² All subgroups [on the trial] had a PFS benefit with the ADC, as well. Then when we saw the overall survival [OS] results that led to a much more enthusiastic response related to this drug. The median OS [with sacituzumab govitecan was] 14.5 months [95% CI, 13.0-16.0] vs 11.2 months [95% CI, 10.2-12.6] with standard therapy [HR 0.79; 95% CI, 0.65-0.95; P = .0133]. [Sacituzumab govitecan] is a medication that is life prolonging and can improve OS, [and did in all the subgroups].2 This resulted in the FDA approval of this agent.³

How does the patient’s Trop-2 expression impact the use of this therapy?

In terms of biomarkers, the question comes up that since the drug targets Trop-2, should we check for Trop-2 in the tissue? The answer is no. In the clinical study, [they looked at patients with] a Trop-2 score of less than 100 vs more than 100 [for patients given sacituzumab govitecan]. Based on those scores, the survival outcomes were similar in terms of improvement with sacituzumab govitecan^.2 Median PFS was around 5 months in both groups [while median OS] was around 14 to 15 months in each Trop-2 expression group with sacituzumab govitecan, in large part because the drug has a bystander effect.² So even if the tumor has low expression of Trop-2, so a low Trop-2 tumor, because of the bystander effect it can then impact the other [cancer] cells.

^References

^{1. Rugo HS, Bardia A, Marmé F, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022;40(29):3365-3376. doi:10.1200/JCO.22.01002}

^{2. 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}

^{3. FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer. FDA. February 3, 2023. Accessed October 13, 2023. https://tinyurl.com/mrxx2kek}