A recent real-world analysis sheds light on the practical use, effectiveness, and tolerability of sacituzumab govitecan (SG) in the treatment of metastatic triple-negative breast cancer (mTNBC) as a second-line or later therapy. The study was presented at the ESMO 2023 Congress (Abstract 393P) held in Madrid, Spain.
SG is an antibody drug conjugate directed toward TROP2 and has gained approval in multiple countries for patients with mTNBC who have undergone at least two prior systemic therapies, including one for metastatic disease. The pivotal ASCENT study (NCT02574455) demonstrated SG's superiority in terms of efficacy when compared to single-agent chemotherapy, while maintaining a manageable safety profile (N Engl J Med 2021; doi: 10.1056/NEJMoa2028485). The present study aims to provide a real-world perspective on SG dosing and clinical outcomes in patients with mTNBC who received SG as a second-line or later treatment in the U.S.
This retrospective cohort study harnessed de-identified electronic health records from the ConcertAI database, focusing on patients ages 18 or older with mTNBC treated with SG in second line or later between April 2020 and May 2022, ensuring a minimum data accrual of 3 months. Clinical outcomes, including real-world overall survival (rwOS), time to next treatment or death (TTNTD), and real-world progression-free survival, were assessed from the start of SG treatment (the index date) using Kaplan-Meier methods.
A total of 230 female patients were included in the analysis with a median age of 60 years. The cohort comprised 26 percent Black patients and 17 percent had an ECOG performance status of 2 or higher. Notably, 66 percent of patients were treated in community settings. The median follow-up duration was 7.2 months with an interquartile range spanning from 3.9 to 11.1 months.
Real-world outcomes for SG in mTNBC remained consistent across various stratified analyses, including race, concomitant use of G-CSF, and treatment-free interval duration. Approximately 58 percent of the patients had received G-CSF during SG treatment, with 74 percent of them having a history of G-CSF use. The median time from the start of SG treatment to G-CSF use was 8.5 days. SG was discontinued due to toxicity in 17 patients (7%).
The real-world analysis of SG in patients with mTNBC offers compelling insights into the effectiveness of this treatment. Among patients receiving SG as a second-line therapy, the study revealed a median rwOS of 13.9 months, with an encouraging 12-month rwOS rate of 51 percent. In the 3L setting, the median rwOS was 8.4 months, with a 12-month rwOS rate of 35 percent. For all patients in the analysis, the combined rwOS yielded a median of 10.0 months, with a 12-month rwOS rate of 40 percent. Additionally, the study reported a median TTNTD of 4.6 months.
For further insights into the study, Oncology Times reached out to study author, Kevin M. Kalinsky, MD, MS, a medical oncologist, Director of the Glenn Family Breast Cancer Center, and Director of Breast Medical Oncology at the Winship Cancer Institute of Emory University.
Oncology Times: What is the rationale behind the use of SG as second-line or later treatment for mTNBC? How does it compare to single-agent chemotherapy in real-world settings?
Kalinsky: "For patients with mTNBC, we administer SG in patients with second-line or later, given results of ASCENT, which compared SG to standard of care chemotherapy, including eribulin, capecitabine, gemcitabine, or [vinorelbine]. In ASCENT, there was a statistically significant and clinically meaningful improvement in response, progression-free survival, and overall survival.
"We performed a study in the real-world setting, as patients in clinical trials do not always reflect the patients we treat in clinic. In a racially diverse patient population, a median real-world overall survival of 13.9 months was found if patients are treated in the second line. In our real-world study, 26 percent of patients were reported as Black, as opposed to ~12 percent in the ASCENT trial. Concomitant administration of G-CSF was observed in 58 percent of all patients, with most having received G-CSF with prior anticancer therapy. We saw outcomes were similar to the overall population when stratifying by factors, including race, G-CSF use, and treatment-free interval."
Oncology Times: How might the results from this real-world analysis influence clinical decision-making and the use of SG in second-line and later settings for mTNBC? What are the implications for future research in this area?
Kalinsky: "These data are reassuring in that we have relatively similar efficacy and tolerability in our real-world study as seen in the landmark ASCENT trial. These data reaffirm the benefit and potential side effects that we can see in our patients, including a population with a higher proportion of under-represented minorities. Future real-world data should continue to focus on predictors of toxicity and how to best sequence drugs approved in mTNBC, including antibody drug conjugates."
Dibash Kumar Das is a contributing writer.