Aditya Bardia, MD, MPH, Examines Final Data for Sacituzumab Govitecan Vs Physician’s Choice Therapy in Previously Treated, Metastatic TNBC

Final efficacy results from the phase 3 ASCENT trial (NCT02574455) comparing sacituzumab govitecan (Trodelvy) vs physician’s choice of single-agent chemotherapy in patients with previously treated metastatic triple-negative breast cancer (TNBC) were recently presented in a poster at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and reinforced the agent’s position in this space.¹

Aditya Bardia, MD, MPH, associate professor of medicine at Harvard Medical School, medical oncologist at the Massachusetts General Hospital, and lead investigator of this study, spoke with CancerNetwork^® about the updated overall survival (OS), progression-free survival (PFS), and safety data in the overall population as well as results in the subgroup without brain metastases.

Overall, the updated results showed that sacituzumab govitecan improved quality of life versus single-agent chemotherapy across all 5 primary domains of global health status, physical functioning, role functioning, fatigue, and pain. Statistically significant and clinically meaningful improvements in OS were noted in both the overall (HR, 0.51; P <.0001) and the brain metastasis–negative (HR, 0.48; P <.0001) populations. Similarly, improvement in PFS was noted overall (HR, 0.41; P <.0001) and in those without brain metastases (HR, 0.39; P <.0001).

CancerNetwork^®: What was the rationale for the phase 3 ASCENT trial?

Bardia: The ASCENT trial evaluated sacituzumab govitecan vs standard chemotherapy for patients with pretreated metastatic TNBC. This was important because patients with TNBC have worse prognosis as compared with other [disease subsets]. It tends to affect African Americans [and] young patients more, and the response with standard chemotherapy, including PFS [and] OS, is quite poor. Clinically, there’s an unmet need for better therapies for patients with metastatic TNBC.

What really stood out to you regarding the study findings?

At 2022 ASCO, we presented final results from the phase 3 ASCENT trial, which included further efficacy and safety data. Previously, we had presented that sacituzumab govitecan demonstrated significant both PFS and OS benefit as compared with standard chemotherapy for pretreated patients with metastatic TNBC, and this was [originally] published in the New England Journal of Medicine.² At 2022 ASCO, we provided final results with additional follow up with final database lock. The analysis essentially showed results that were consistent with what was reported previously. In the final database lock, you could see improvement in PFS and OS with sacituzumab govitecan as compared with standard chemotherapy [with results] more than doubling. There were also patients without disease progression at the 2-year landmark, so it confirms the efficacy that was seen previously with additional follow up.

Was there anything new regarding safety or was it consistent with what we’ve previously seen with this agent?

The safety profile was consistent with what had been previously reported. The most common adverse effect with sacituzumab govitecan was neutropenia; besides neutropenia, anemia and diarrhea were also seen, and the incidence was higher in patients receiving sacituzumab govitecan vs standard chemotherapy. The incidence of interstitial lung disease, or pneumonitis, was essentially not seen with sacituzumab govitecan. There were no grade 3 or 4 [events of] neuropathy AEs that were seen with sacituzumab govitecan. Finally, the other AE that was not seen was cardiotoxicity. These are important considerations when we talk to patients about treatment with sacituzumab govitecan. It’s important to talk to them about neutropenia, diarrhea, alopecia, but also mention adverse effects we do not see, which include interstitial lung disease, neuropathy, or cardiotoxicity.

Are there going to be any future analyses of the ASCENT study that we can look forward to?

The ASCENT trial looked at sacituzumab govitecan vs standard chemotherapy. It was a large trial, so there is interest in additional analyses, such as quality of life, subgroups, [and] biomarkers. At 2022 ASCO, besides the efficacy and AEs we also presented the quality-of-life results. And the study showed that patients receiving sacituzumab govitecan did better in terms of health-related quality of life, which included global health status, physical functioning, role functioning, [and] fatigue pain. [From both an] efficacy and quality-of-life perspective, you saw improvement with sacituzumab govitecan.

How do you potentially foresee this research impacting the treatment paradigm?

The final results from the ASCENT trial confirm that sacituzumab govitecan should be the preferred treatment options in the second-line setting and beyond for patients with metastatic TNBC.

Were there any other ASCO takeaways that you wanted to share?

At ASCO, there was a lot of excitement related to antibody-drug conjugates [ADC]. Five or 10 years ago, we were not talking much about ADCs. But at ASCO, you saw the excitement related to ADCs in breast cancer, and [in the] future, we’ll see more ADC combination therapy.

References

1. Bardia A, Tolaney SM, Loirat D, et al. Sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (pts) with previously treated, metastatic triple-negative breast cancer (mTNBC): Final results from the phase 3 ASCENT study. J Clin Oncol. 2022;40(suppl 16):1071. doi:10.1200/JCO.2022.40.16_suppl.1071
2. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. 2019;380(8):741-751. doi:10.1056/NEJMoa1814213