Sacituzumab govitecan shows ‘enduring benefits’ in metastatic breast cancer subset
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Key takeaways:
- Researchers reported median OS of 14.5 months with sacituzumab govitecan vs. 11.2 months with physician’s treatment of choice.
- No new safety signals occurred with the longer follow-up.
CHICAGO — Sacituzumab govitecan continued to show significant improvement in OS among patients with heavily pretreated metastatic hormone receptor-positive breast cancer, according to final OS results of the phase 3 TROPiCS-02 study.
The findings, presented at ASCO Annual Meeting, also showed no new adverse events associated with sacituzumab govitecan (Trodelvy, Gilead) — a Trop-2-directed antibody-drug conjugate — after nearly 13 months of follow-up.
Rationale and methods
As Healio previously reported, the randomized phase 3 TROPiCS-02 study included 543 patients with ECOG performance status of 0 or 1 who had received two to four prior lines of chemotherapy and at least one line of endocrine therapy for metastatic breast cancer.
Researchers randomly assigned patients 1:1 to sacituzumab govitecan (n = 272; median age, 57 years; 68% white), dosed at 10 mg/kg IV on days 1 and 8 every 21 days, or physician’s choice of treatment (n = 271; median age, 55 years; 66% white).
Treatment continued until disease progression or unacceptable toxicity.
“We previously presented results from the primary efficacy data, which showed a significant improvement in PFS with sacituzumab govitecan compared with treatment of physician’s choice chemotherapy,” Sara M. Tolaney, MD, MPH, chief of the division of breast oncology at Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, told Healio. “We also previously presented data from the second interim analysis, which showed sacituzumab govitecan led to an improvement in OS at that time with a 3.2-month difference between the two arms, and also led to significant improvement in objective response rate and improvement in duration of response. Now we present the final OS analysis with about 13 months follow-up.”
Findings
At the time of data cutoff, researchers observed 437 OS events, with 22 new deaths in the sacituzumab govitecan group compared with 25 deaths in the comparator group since the second interim analysis.
Results showed median OS of 14.5 months with sacituzumab govitecan vs. 11.2 months with physician’s treatment of choice (HR = 0.79; 95% CI, 0.65-0.95). Researchers reported OS rates for sacituzumab govitecan compared with physician’s treatment of choice of 60.9% (95% CI, 54.8-66.4) vs. 47.1% (95% CI, 41-53) at 1 year, 39.2% (95% CI, 33.4-45) vs. 31.7% (95% CI, 26.2-37.4) at 18 months and 25.6% (95% CI, 20.4-31.1) vs. 21.1% (95% CI, 16.3-26.3) at 2 years.
“Sacituzumab govitecan continued to improve PFS, with a nearly 1.5-month difference between the two arms, and continued to show a significant improvement in OS, with a 3.3-month difference between the two arms,” Tolaney said. “Results of additional analysis of outcomes by Trop-2 expression, as well as HER2 immunohistochemistry status, showed the efficacy of sacituzumab govitecan is independent of Trop-2 expression and HER2 immunohistochemistry status.
In addition, researchers observed no new safety signals with the longer follow-up.
“These updated data continue to show enduring benefits with sacituzumab govitecan at longer follow up and reinforce sacituzumab govitecan as a new standard therapy for metastatic hormone receptor-positive disease,” she continued.
Implications
Antibody-drug conjugates have demonstrated greater efficacy than standard chemotherapy for patients with breast cancer, Tolaney told Healio.
“These findings have opened up a whole new field of therapeutics for breast cancer that is revolutionizing outcomes for our patients and fits so nicely in with the direction the field is going,” she said. “The question now becomes whether we can use sacituzumab govitecan even earlier than what we used in this trial. There is an ongoing study looking at sacituzumab govitecan in the first-line setting for metastatic hormone receptor-positive disease. So, we will learn more about what the efficacy looks like for sacituzumab govitecan in less-pretreated patients.”
There is also interest in sacituzumab govitecan for early-stage breast cancer, Tolaney added.
“There is an ongoing study for patients with early-stage triple-negative breast cancer who have residual disease after preoperative chemotherapy where patients are randomly assigned to sacituzumab govitecan or treatment-of-choice therapy,” she said. “We’re going to see a lot more to come for sacituzumab govitecan, not just for metastatic hormone receptor-positive disease, but also for early-stage triple-negative disease and even in earlier lines for metastatic triple-negative cancers where there are ongoing registration trials for sacituzumab govitecan in the first-line metastatic setting. ASCENT-03 and ASCENT-04 are looking at sacituzumab govitecan for first-line metastatic triple-negative disease and either PD-L1-positive or PD-L1-negative disease. There is a lot more to come for this agent.”
Perspective
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Alan B. Astrow, MD
This study gives us added confidence in previously reported results showing this medication has value in the treatment of patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have received prior endocrine therapy and chemotherapy.
Often in this population, the patient’s cancer progresses and we run out of potentially effective treatments. This is a new therapy that we can offer patients whose disease has progressed despite several previous chemotherapy treatments. That’s why this study has value — it gives us another potentially effective treatment that can extend the patient’s life. A patient will live longer as a result of receiving this treatment. It doesn’t extend the patient’s life by a great deal, but even a modest improvement in survival is a significant achievement. It’s a significant benefit to the patient and a significant advance in the field of medical oncology.
Some key unanswered questions remain. Since we know this medication is useful when a patient has received many previous treatments, it’s possible it could be even more useful if we give patients these agents earlier in the course of treatment. However, we don’t know that yet.
Additionally, we’ve seen some serious issues with low blood counts, neutropenia and gastrointestinal side effects, particularly in patients whose bodies have been weakened by both the cancer itself and the previous treatments they have received. There is nausea, vomiting and diarrhea, which can be quite significant. So, we have to be very careful in the use of this drug, and if the patient is experiencing significant side effects, we may have to reduce the dose. If we do reduce the dose, there’s good reason to hope that the drug will maintain its efficacy with fewer side effects.
We await more published data to show that lower doses of the drug are still effective while reducing toxicity. That’s the question we need to answer in the future.
New York-Presbyterian Brooklyn Methodist Hospital
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Tolaney SM, et al. Abstract 1003. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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