Results from the confirmatory Phase III ASCENT study showed that sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy®; Immunomedics) significantly extended overall survival (OS) and improved overall response rate (ORR) and clinical benefit rate (CBR), compared to treatment of choice (TPC) standard single-agent chemotherapy in brain metastases-negative patients with advanced or metastatic triple-negative breast cancer (mTNBC) who previously received at least two prior therapies for metastatic disease.

These results of the study were presented as a late-breaking abstract (Abstract# LBA17) at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

Triple-negative breast cancer is an aggressive type of breast cancer, accounting for up to 20% of all breast cancers. The disease is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American and Hispanic women. TNBC cells do not have estrogen or progesterone hormone receptors or very much of the human epidermal growth factor receptor 2 (HER2) hence the term triple-negative. This means that medicines that target these receptors are not typically effective in TNBC. There is currently no approved standard of care for people with previously-treated mTNBC.

A new standard of care
“The randomized Phase III study results confirm that sacituzumab govitecan should be considered as a new standard of care in patients with third-line mTNBC,” noted Aditya Bardia, MD, MPH, Director of Precision Medicine at the Center for Breast Cancer, Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School, who will give an oral presentation of the study at the ESMO Congress.

“Ongoing studies are evaluating sacituzumab govitecan in earlier lines of therapy, including the neoadjuvant and adjuvant settings, in combination with other targeted agents, and in patients with hormone receptor-positive, human epidermal growth factor 2-negative metastatic breast cancer, which will help accelerate our efforts to further improve outcomes for patients with breast cancer,” Bardia added.

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Despite having received a median of four prior anticancer regimens, patients treated with sacituzumab govitecan in the ASCENT study showed a statistically significant and clinically meaningful improvement in OS with a median of 12.1 months (95% confidence interval (CI), 10.7-14.0) versus 6.7 months (95% CI, 5.8-7.7) for chemotherapy, with a hazard ratio of 0.48 (95% CI, 0.38-0.59; p<0.0001).

Aditya Bardia, M.D., MPH is Assistant Professor, Medicine, Harvard Medical School, and Attending Physician, Medical Oncology, Massachusetts General Hospital. Photo courtesy: © 2020 Dana-Farber / Harvard Cancer Center. Used with permission.

Sacituzumab govitecan also demonstrated a statistically significant improvement in ORR (35%) and CBR (45%) compared to chemotherapy (5% and 9%, respectively). Ten complete responses were observed (4%) in the Trodelvy arm compared with two (1%) in the control group.

As of data cutoff on March 11, 2020, 15 patients continued to receive sacituzumab govitecan treatment while no patient remained on a study in the TPC control arm.

“We believe these remarkable results should facilitate the establishment of sacituzumab govitecan as a new standard of care in patients with third-line mTNBC,” said Loretta M. Itri, M.D., Chief Medical Officer of Immunomedics.

“We are working very collaboratively with FDA under the RTOR program to submit a supplemental Biologics License Application to have sacituzumab govitecan’s label expanded to include these confirmatory new data. Additionally, we plan to submit a Marketing Authorization Application to the European Medicines Agency in the first half of 2021 in order to make this important new treatment available to mTNBC patients in Europe.”

Manageable safety profile
Sacituzumab govitecan is an antibody-drug conjugate (ADC) directed against Trop-2, a cell-surface protein expressed in many solid cancers. The drug binds to Trop-2 and delivers the anti-cancer drug, SN-38, to kill cancer cells.

The drug was well tolerated by patients in the ASCENT study, with a manageable safety profile consistent with the U.S. Food and Drug Administration (FDA)-approved label; no new safety signals were observed in the ASCENT study. Adverse events leading to treatment discontinuation were low and similar (Trodelvy 4.7% vs TPC 5.4%) in both arms of the study.

Clinically meaningful
“We are delighted to witness the clinically meaningful survival benefit sacituzumab govitecan is bringing to mTNBC patients. These outstanding results have inspired us to fully demonstrate the potential of this valuable new treatment to improve the outlook of cancer patients worldwide,” said Behzad Aghazadeh, Ph.D., Executive Chairman of Immunomedics.

Sacituzumab govitecan was approved as a third-line treatment for adult patients with mTNBC under the FDA’s Accelerated Approval Program and carries a black box warning for severe neutropenia and severe diarrhea. The most common adverse reactions occurring in 25 or more percent of patients included nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.

The most common Grade 3 or 4 adverse events occurring in more than 5% of patients were neutropenia, white blood cell count decreased, anemia, hypophosphatemia, diarrhea, fatigue, nausea, and vomiting. Two percent of patients discontinued treatment due to adverse events. There were no deaths related to treatment and no severe cases of neuropathy or interstitial lung disease.

Clinical trial
ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT) – NCT02574455.

Highlights of prescribing information
Sacituzumab govitecan-hziy (Trodelvy®; Immunimedics)[Prescribing Information]

National Drug Code List
NDC CODE: 55135-132 [Package Description]

[1] Syed YY. Sacituzumab Govitecan: First Approval. Drugs. 2020;80(10):1019-1025. doi:10.1007/s40265-020-01337-5

An edited version of this article was published in ADC Review | Journal of Antibody-drug Conjugates.

Featured image: ESMO congress. Photo courtesy: © 2016 – 2020  European Society for Medical Oncology. Used with permission.

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