Tiffany A. Traina, MD, discusses the significance of the FDA approval of sacituzumab govitecan for patients with metastatic hormone receptor-positive, HER2-negative breast cancer and expanded on the data from TROPiCS-02 that supported the approval.
Along with improvements in progression-free survival (PFS) and other efficacy outcomes, sacituzumab govitecan-hziy (Trodelvy) can also provide improved quality of life (QOL) over traditional chemotherapy as a later-line option for pretreated patients with metastatic hormone receptor (HR)–positive, HER2-negative breast cancer, according to Tiffany A. Traina, MD.
On February 3, 2023, the FDA approved sacituzumab govitecan for the treatment of adult patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.1 Data from the phase 3 TROPiCS-02 trial (NCT03901339) showed that patients treated with sacituzumab govitecan (n = 272) achieved a median overall survival (OS) of 14.4 months (95% CI, 13.0-15.7) vs 11.2 months (95% CI, 10.1-12.7) in patients treated with physician’s choice of chemotherapy (n = 271). This translates to a 21% reduction in the risk of death (HR, 0.789; 95% CI, 0.646-0.964; P = .02).2
Furthermore, the antibody-drug conjugate (ADC) elicited a median PFS of 5.5 months (95% CI, 4.2-7.0) compared with 4.0 months (95% CI, 3.1-4.4) with chemotherapy (HR, 0.661; 95% CI, 0.529-0.826; P = .0003).
“Having sacituzumab govitecan FDA approved for patients with HR-positive breast cancer continues to fill an unmet need for that later-line population that has exhausted sequencing through their endocrine therapies, or has primary refractory disease to endocrine therapies, despite being HR-positive,” Traina explained in an interview with OncLive®.
Traina discussed the significance of the FDA approval of sacituzumab govitecan for patients with metastatic HR-positive, HER2-negative breast cancer and expanded on the data from TROPiCS-02 that supported the approval. Traina is a medical oncologist and the vice chair of Oncology Care in the Department of Medicine and the section head for the Triple Negative Breast Cancer Clinical Research Program at Memorial Sloan Kettering Cancer Center.
Traina: It is always significant when we have another highly effective agent FDA approved for our patients who are under treatment for metastatic breast cancer. Sacituzumab govitecan [gives] patients with HR-positive breast cancer yet another line-of-therapy opportunity that we see is now superior to treatment with physician’s choice of chemotherapy.
The TROPiCS-02 trial was a large, randomized study that compared sacituzumab govitecan, the ADC, as a single agent, [vs] treatment of physician’s choice chemotherapy. These were our typical agents, [including] capecitabine, vinorelbine, gemcitabine, [or] eribulin.
The patient population [in the trial] were women with metastatic HR-positive, HER2-negative breast cancer, who had seen at least 1 line of endocrine therapy, had [received] a prior CDK4/6 inhibitor, and had at least 2 prior lines of chemotherapy for the treatment of their metastatic breast cancer. [This was] what is traditionally a very refractory treatment population.
More than 500 women were [randomly assigned] to treatment, and the primary end point for this study was PFS. What we saw in terms of efficacy was that this trial met its primary end point for blinded [independent central review]–assessed PFS.
Sacituzumab govitecan was superior to treatment with physician’s choice chemotherapy by [34%] in terms of PFS, and that was the median difference. The absolute differences were measured in a [1.5-month] incremental difference. Yet, if you looked at landmark analyses, at 6, 9, and 12 months, at each of these time points, patients receiving sacituzumab govitecan were more likely to be progression free than patients who were receiving standard chemotherapy.
The trial certainly met its prespecified primary end point for PFS.
In terms of other efficacy end points, such as response rates, we also saw that sacituzumab govitecan outperformed treatment of physician’s choice chemotherapy.
In many of our clinical trials, we're often assessing toxicity as judged by the investigators. However, QOL metrics are increasingly important to hear [about] the impact of therapy directly from the patient voice.
In TROPiCS-02, QOL metrics, including time to deterioration of QOL end points, were measured. We can see in these global health status scores and fatigue scales that patients receiving sacituzumab govitecan had better outcomes from a patient perspective in terms of QOL. Sacituzumab govitecan had longer time to deterioration in those QOL metrics.
There were no surprising AEs reported in the TROPiCS-02 trial, relative to sacituzumab govitecan. We [saw] cytopenias and neutropenia, which is probably one of the most common all-grade hematologic toxicities, but febrile neutropenia remained relatively uncommon. Grade 3 diarrhea looked quite comparable to the data [from the phase 3 ASCENT trial (NCT02574455)], with [10% of patients experiencing] grade 3 or greater diarrhea with sacituzumab govitecan [during TROPiCS-02].
It is of note to call out that in contrast to some of the other ADCs, in the sacituzumab govitecan arm [in TROPiCS-02], there were no occurrences of interstitial lung disease [ILD], and there is a 1% [rate] of ILD in the treatment of physician’s choice arm, so [ILD] does not appear to be a concern with sacituzumab govitecan. Otherwise, there were no other significant, standout AEs.
The choice of systemic agents is a shared decision-making experience. I would not say there is an absolute contraindication, but relatively, I would talk to my patients about cytopenias and the potential need for growth factor support. These are heavily pretreated patients.
The [dosing] schedule [for sacituzumab govitecan] is intravenous 2 weeks on, 1 week off, so that has impact for certain women's lives. There is a risk of alopecia with this therapy. However, none of those are absolute contraindications.
Traditionally, once we've exhausted these endocrine- and targeted-therapy options, we've gone through serial cytotoxic chemotherapies that have been active and available for years, but unfortunately, are not adequate. This is palliative therapy, not curative, unfortunately. [Therefore], to have a powerful agent that can prolong PFS, improve response rates, and [improve] QOL over our prior options is important for our patients.