The incidence of hormone receptor positive/HER2 negative metastatic breast cancer (HR+/HER2- mBC) tends to be more prominent in older adults, especially those above the age of 65. In addition, prognosis in these patients is more likely to be poorer due to associated comorbidities, increased toxicity, and reduced chemotherapy efficacy. The TROPiCS-02 phase 3 clinical study investigated and compared the effects of sacituzumab govitecan (SG), a TROP-2 directed antibody-drug conjugate, and the treatment of physician’s choice (TPC) in patients with HR+/HER2- mBC. Aditya Bardia, MD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, and colleagues presented their analysis of the clinical outcomes of these treatments in varied age subgroups at the 2023 San Antonio Breast Cancer Symposium.

Participants in the study included 543 patients with HR+/HER2- mBC who had previously undergone at least one endocrine therapy, taxane, and CDK4/6 inhibitor, as well as 2 to 4 prior chemotherapy lines for metastatic breast cancer. These patients were randomly assigned to either the sacituzumab govitecan group (n = 272) (which involved intravenous application of sacituzumab govitecan in measured doses on specific days), or the TPC group (n = 271). Out of these, 27% of the SG group and 25% of the TPC group were aged 65 or above, and 6% of the SG and 3% of the TPC group were aged 75 or above. The primary and secondary end points of the study were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Given the focus on age subgroups, a post hoc analysis was carried out to compare clinical outcomes in categories of < 65 vs ≥ 65, and < 75 vs ≥ 75.

The study outcomes revealed that sacituzumab govitecan treatment resulted in a longer median PFS and OS across all age subgroups compared to TPC, with varying hazard ratios (HRs), signifying a notable treatment benefit. Specifically, HRs for PFS with SG vs TPC were 0.69, 0.59, 0.70, and 0.30 for the < 65, ≥ 65, < 75, and ≥ 75 age subgroups, respectively. The HRs for overall survival were 0.81, 0.80, 0.82, and 0.56 in these respective subgroups. The ORR was notably higher with SG compared to TPC, with the exception of the ≥ 75 age subgroup. The duration of response was also longer with sacituzumab govitecan across all age subgroups; however, it was not estimable in the ≥ 75 age subgroup.

In terms of safety, grade 3 or higher treatment-emergent adverse events were more common in the ≥ 75 subgroup whether treated with sacituzumab govitecan (81%) or TPC (71%), compared to other age subgroups, where the range was between 60% and 73%. Adverse events leading to dose reduction or treatment discontinuation were also more common in older patients, irrespective of the treatment group. While there was a slight increase in toxicity for elderly patients, the beneficial effects of sacituzumab govitecan were shown to be consistently advantageous over TPC across age subgroups. Despite this, the study’s authors noted that the sample size in the ≥ 75 subgroup was small, which could limit the interpretation of results for that particular age group.

In summary, the TROPiCS-02 study showed that sacituzumab govitecan was beneficial for PFS and OS in patients with HR+/HER2- mBC across varied age subgroups, lining up with the intent-to-treat population. Although there is a small rise in toxicity with sacituzumab govitecan, particularly for patients older than 75, sacituzumab govitecan showed a preferable benefit/risk profile, with an efficacy benefit and tolerable toxicity for these patients. Therefore, the study concludes that sacituzumab govitecan presents an acceptable therapeutic alternative for HR+/HER2- metastatic breast cancer patients across age groups.

Bardia A, Schmid O, Tolaney S, et al. Clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2‒ metastatic breast cancer. Presented at: the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; Abstract PO5-21-09.