Sacituzumab govitecan significantly extends PFS in advanced breast cancer subset
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CHICAGO — Sacituzumab govitecan significantly extended PFS vs. single-agent chemotherapy among patients with heavily pretreated hormone receptor-positive, HER2-negative advanced breast cancer, according to study results.
The findings, presented during ASCO Annual Meeting, also showed sacituzumab govitecan (Trodelvy, Gilead), an antibody-drug conjugate consisting of an anti-Trop-2 antibody, had a manageable safety profile among the study population.
Rationale and methods
“Hormone receptor-positive, HER2-negative breast cancer is the most common subset of breast cancer worldwide in both the early and metastatic setting. Among this patient population, about 20% to 30% of those who present with early-stage disease will eventually develop metastatic disease,” Hope S. Rugo, MD, professor of medicine and director of breast oncology and clinical trials education at University of California, San Francisco, Comprehensive Cancer Center, told Healio. “Although new therapies have improved outcome in both the early- and late-stage setting, patients with advanced disease continue to experience disease progression with resistance developing to each subsequent therapy.”
The current standard of care for patients with advanced hormone receptor-positive, HER2-negative disease is CDK 4/6 inhibitors with endocrine therapy in the first-line setting and then sequential endocrine therapy combined with targeted agents as indicated until either there is no evidence of response or endocrine options have been exhausted, followed by sequential chemotherapy, Rugo added.
“However, sequential chemotherapy in the metastatic setting is associated with declining response rates and increasing toxicity that negatively impacts quality of life,” she said. “Disease control becomes more difficult with later lines of therapy, so for our patients who are doing relatively well but have both endocrine- and chemotherapy-resistant disease, we’re running out of treatment options.”
The randomized, phase 3 TROPiCS-02 study included 543 patients with an ECOG performance status of zero or 1 who had received two to four prior lines of chemotherapy and at least one line of endocrine therapy for metastatic breast cancer. All patients had to have received a taxane and CDK 4/6 inhibitor in any setting.
Study participants had received a median prior three chemotherapy regimens, most (95%) had visceral metastases, 86% received prior endocrine therapy for metastatic breast cancer for 6 months or more, and 38% received CDK 4/6 inhibitors for less than 1 year.
Researchers randomly assigned patients 1:1 to either sacituzumab govitecan (n = 272), dosed at 10 mg/kg IV on days 1 and 8 every 21 days, or physician’s choice of treatment (n = 271), including capecitabine, eribulin, vinorelbine or gemcitabine, until disease progression or unacceptable toxicity.
PFS per RECIST version 1.1 by blinded independent central review served as the primary endpoint, with OS, safety, response and duration of response, as well as quality of life, as secondary endpoints.
Key findings
Results showed median PFS of 5.5 months with sacituzumab govitecan vs. 4 months with physician’s choice of treatment (HR = 0.66; 95% CI, 0.53-0.83).
Landmark analyses were performed due to rapid progression in a subset of patients regardless of treatment in the first two months; PFS was superior at 6, 9 and 12 months for patients treated with sacituzumab. Specifically, PFS rates were 46% vs. 30% at 6 months and 21% vs. 7% at 1 year. Patients had median OS of 13.9 months with sacituzumab govitecan vs. 12.3 months with physician’s choice of treatment, which did not reach statistical significance (HR = 0.84).
Moreover, researchers observed higher objective response rates (21% vs. 14%) and clinical benefit rates (34% vs. 22%) with sacituzumab govitecan vs. physician’s choice of treatment, as well as a longer median duration of response (7.4 months vs. 5.6 months).
In terms of safety, researchers observed grade 3 or higher treatment-associated adverse events among 74% of patients assigned sacituzumab govitecan vs. 60% of those assigned physician’s choice of treatment. The most common included neutropenia (51% vs. 38%) and diarrhea (10% vs. 1%). Treatment discontinuation occurred among 6% of those assigned sacituzumab govitecan and 4% assigned physician’s choice of treatment. One treatment-associated death occurred in the sacituzumab govitecan group.
“All patients in this study had to have received a prior CDK 4/6 inhibitor, which is an important difference from other previous studies, and patients were quite heavily pretreated. It is important for patients to be able to stay on therapy for longer durations because it makes a really big difference,” Rugo said. “The implications here are that we now have a treatment that could potentially offer PFS benefits for patients who received multiple lines of prior chemotherapy and have endocrine-resistant hormone receptor-positive or -negative disease.”
Looking ahead
Rugo stressed the importance of having sequential treatment options for patients.
“Moving the antibody-drug conjugates to early-stage disease is an appealing and exciting next step, so that we could potentially treat patients who have relative resistance to chemotherapy given in the neoadjuvant setting,” Rugo said. “We also may find that giving these agents in the neoadjuvant setting benefits patients who have chemotherapy-resistant disease, where we struggle to find better treatment options,” Rugo said.
For more information:
Hope S. Rugo, MD, can be reached at hope.rugo@ucsf.edu.
Perspective
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Sarah Cate, MD
This is an important study, as approximately 41,000 patients with breast cancer die each year in the United States alone.
This study included a large number of patients who need a second-line therapy in the setting of metastatic breast cancer. Results showed statistically significant improvement in PFS rates at 6 months and 12 months vs. single-agent chemotherapy.
Further follow up will be needed for duration of response, as well as studies with larger numbers of patients. However, this is exciting new research.
Perspective
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Jane Lowe Meisel, MD
We have all been eagerly awaiting results of this trial.
As clinicians, we have seen how well sacituzumab govitecan works in patients with triple-negative breast cancer. These patients with estrogen-positive, endocrine-resistant disease are a great area of unmet need and these cancers can be very difficult to treat.
We have seen here that sacituzumab govitecan tends to work better than chemotherapy when compared. We have many patients on this trial who had a lot of chemotherapy, and the median line of chemotherapy was three. The idea that a patient with such heavily pretreated disease can walk into our office and we can offer them a treatment that will allow them a one-in-five chance of still not having progressed at 1 year is huge from a clinical standpoint. This will definitely offer a wonderful option for our patients and this is what we need — incremental options and options that may be better than chemotherapy. This truly represents a step forward for the field.
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Rugo HS, et al. Abstract LBA1001. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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