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Study: Smart drug shows promising results for treatment of metastatic triple-negative breast cancer

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Contents

At a glance Guidelines
Findings                             Questions for your doctor                 
Clinical trials Limitations
Media coverage Resources


STUDY AT A GLANCE

This study is about:

Whether a new drug, IMMU-132, also called sacituzumab govitecan-hziy, is safe and effective for treating triple-negative breast cancer.

THIS INFORMATION HAS BEEN UPDATED on 04/27/20:  Based on the results from the study reviewed in this XRAY, the U.S. Food and Drug Administration () has approved sacituzumab govitecan-hizy (Trodelvy), as a treatment for people with   who have received at least two prior therapies for  disease.  Please refer to our most updated review on this agent for additional information. 

Why is this study important?

New, more effective therapies are needed treat triple-negative breast cancer. This study tests a new type of drug; “smart” drugs combine an antibody that delivers the smart drug to tumor cells and a chemotherapy drug (SN-38) that kills the tumor cells.

Study findings: 

  • Adverse events were comparable or lower to similar trials. Adverse events included:
  • 4 patient deaths that were attributed to progression of their cancer, not the drug treatment.
  • Severe adverse events occurred for 35 patients (37%), including fever with low white blood cell count, vomiting, nausea, diarrhea and labored breathing.
  • 3 patients (2.8%) discontinued treatment because of adverse events (2 were drug related and the third was due to unrelated high blood pressure).
  • The other major adverse events were digestive problems—mostly diarrhea, nausea and vomiting (grade 3 severe) in 19% and any grade (mild to potentially life-threatening) in 94% of patients.
     
  • 33% of patients had a partial or complete shrinkage of their tumors.
  • 3 patients had a complete response to the drug.
  • 45% of patients had partial, complete shrinkage or no growth of their tumors.
     
  • Median progression-free survival (PFS) or time before tumors grew was 5.5 months, more than double the time of the patients' last line of therapy (2.5 months).
  • Overall survival (OS) or how long patients survived was 13 months.
  • 6 patients continued to have a response beyond 12 months, at the time the study was published.

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What does this mean for me?

If you have triple-negative breast cancer (mTNBC), be aware that new treatment therapies are being developed if other single-line therapies fail. The smart drug tested in this study is not yet approved by the . However, the ASCENT trial, an ongoing Phase III clinical trial that is currently enrolling participants, is further testing the efficacy of this drug. Additionally, Tecentriq (atezolizumab) plus nab-paclitaxel was recently approved the as a first-line treatment for women with triple-negative breast cancer whose tumors are positive for the protein. In contrast, the smart drug IMMU-132 can be used to treat women regardless of the status of her tumor (positive or negative).

Posted 4/162/19

References

Bardia A, Mayer IA, Vahdat LT, et al. “Sacituzumab Govitecan-hziy in refractory triple-negative breast cancer.” New England Journal of Medicine. 2019 (380):741-751. DOI:10.1056/NEJMoa1813213.
 

Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

This article is relevant for:

People with metastatic, triple-negative breast cancer

This article is also relevant for:

Triple negative breast cancer

People with a genetic mutation linked to cancer risk

Breast cancer survivors

Women under 45

Women over 45

Metastatic cancer

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Questions to Ask Questions to Ask Your Doctor

  • Are any new therapies for appropriate for my treatment?
  • Do I qualify for any clinical trials?
  • What are the risks and benefits of participating in a clinical trial?
  • What is the expected length of progression-free survival for my line of treatment?

Who covered this study?

Science Daily

New 'smart drug' shows promise for metastatic triple-negative breast cancer This article rates 3.0 out of 5 stars

Specialty Pharmacy News

Aggressive breast cancer type shows response to new 'smart drug' This article rates 2.5 out of 5 stars

How we rated the media

IN-DEPTH REVIEW OF RESEARCH

Study background:

(), accounts for 15% of all breast cancers. It is an aggressive cancer which may be difficult to treat. is more common in younger women and black women.

While headway has been made treating other types of breast cancer, treatment and survival rates have remained largely unchanged in the last 20 years. Single-agent chemotherapy is the current standard of care, although only 10-15% of patients show clinical response and progress after 2-3 months. This may change given the recent IMpassion 130 clinical study of atezolizumab (Tecentriq) and nab-paclitaxel. This trial reported 7.4 months of progression-free survival in previously untreated TNBC patients. This led to recent approval of atezolizumab plus nab-paclitaxel for PD-L1-positive mTNBC. ( is a molecule on the surface of some tumor but not all.)

Aditya Bardia and colleagues report results of an early clinical trial to test the safety and effectiveness of a new class of therapy for treatment of triple-negative breast cancer in the New England Journal of Medicine in February 2019. This uses IMMU-132 (also called sacituzumab govitecan-hziy), a so-called "smart" drug. IMMU-132 consists of a two-part molecule that fuses a targeting molecule (the hRS7 antibody) to a chemotherapy drug (the cancer-killing drug SN-38). The antibody portion of the smart drug binds to the surface of tumor cells and delivers the chemotherapy to the tumor cells, which are then destroyed. SN-38 then spreads to neighboring tumor cells, killing them as well. 

In contrast to Tecentriq, the smart drug IMMU-132 does not depend on the status of the tumor (both PD-LI-positive or -negative tumors are a potential target).

Based on promising preliminary results with 69 patients, the designated IMMU-132 as a breakthrough therapy, allowing enrollment for patients who have had two or more prior therapies for mTNBC. This study looks at safety and effectiveness in all mTNBC patients who were treated with IMMU-132.

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Researchers of this study wanted to know:

Whether the new drug IMMU-132 (sacituzumab govitecan-hziy) is safe and effective for treating triple-negative breast cancer.

Populations looked at in this study:

Participants were 108 individuals with confirmed triple-negative breast cancer. Their median age was 55 years; 82 (76%) were white, 8 (7.4%) were black, 3 (2.8%) were Asian and 4 (3.7%) were Native American, Hispanic, Dominican or of mixed race; 11 (10%) declined to state their race. All of the women had cancer that was measurable by CT or scans. All of their cancers had progressed after two prior lines of treatment for disease prior to this study; they were no longer benefiting from their prior treatment. (Patients had a median of three prior therapies, ranging from 2-10 therapies.)

This group of 108 patients was a subset of a larger study of 420 patients with a variety of epithelial cancers, including colon, liver, stomach, ovarian, lung, and pancreatic cancers. Patients with brain metastases were excluded unless they were disease free and symptom free for 3 months and were not being treated with high-dose steroids.

Study design:

The objective of this phase 1/2 single treatment trial was to determine the effectiveness, type and rate of adverse events that occurred with treatment with IMMU-132. Patients were treated with IMMU-132 on day 1 and on day 8 every 3 weeks until their cancer either progressed (grew) or an unacceptable occurred. Dose reductions may have been tried for patients who experienced adverse events.

The measured points were:

  • rate and type of adverse events
  • objective response rate (ORR) or whether the tumor(s) shrank in response to treatment using the Response Evaluation Criteria in (RECIST) 1.1.
  • duration of response
  • clinical benefit, defined as complete or partial response or stable disease for 6 months.
  • progression-free survival (PFS) or length of time before tumors grew
  • overall survival (OS) or length of patient survival

Response rates were additionally evaluated by external reviewers to confirm results.

Study findings: 

Adverse events were comparable or lower to similar trials.

Adverse events included:

  • 4 patient deaths that were attributed to disease progression, not the drug treatment.
     
  • Severe adverse events occurred for 35 patients (37%) including febrile neutropenia (fever in patient with low white blood cell count), vomiting, nausea, diarrhea and labored breathing.
     
  • 3 patients (2.8%) discontinued treatment because of adverse events (2 drug related and the third due to unrelated high blood pressure).
     
  • 10 patients (9.3%) had grade 0-2 febrile neutropenia.
     
  • The other major adverse events were GI problems—predominantly diarrhea and nausea and vomiting that was grade 3 (severe) in 19% of patients and any grade (mild to potentially life-threatening) in 94%.

The adverse events observed among patients with were similar to those seen for all patients with any cancer treated with this drug. The most severe events were impacts on red or white blood cells (anemia and neutropenia). Other common, less severe impacts were diarrhea and nausea. The rates of these adverse events were similar or lower than other treatments for TNBC (e.g., in the EMBRACE studies of pretreated mTNBC patients, 13% of patients treated with eribulin and 15% of patients treated with a physician’s choice of treatment discontinued treatment, compared to 3% in this study).

One-third of patients had a partial or complete shrinkage of tumors

Objective response rate (ORR) or whether the tumor(s) shrank in response to treatment was one of the secondary endpoints of this trial.

  • 3 patients had a complete response and 33 had a partial response (a total ORR of 33% among the 108 patients).
     
  • The 33% overall ORR in this study was lower than in the IMpassion 130 trial, which found an ORR of 45% for the combined therapy and 33% for atezolizumab plus . However, IMpassion 130 trial participants had not been previously treated for cancer, whereas the participants in this study previously experienced failure with an average of three lines of other therapies. This suggests that on average, their cancers were more advanced at the outset. The 33% ORR is higher than the EMBRACE study with eribulin (an ORR of 12%), which enrolled patients who had been pretreated with other lines of therapy.

This study observed clinical benefit, defined as complete or partial response or stable response (less than 20% change in tumor size) in 45.4% of participants.

Length of time before cancer progressed

  • The median duration of response was 7.7 months. Blinded (anonymous) reviewers determined a longer median duration of response of 9.1 months.
     
  • At the data cutoff point for this study, 6 patients had an ongoing response greater than 12 months.
     
  • Median progression-free survival (PFS) or time before tumors grew substantially was 5.5 months. This PFS is more than twice the time of the patients' last line of therapy (2.5 months). Estimated PFS at 6 months was s 42%; estimated PFS at 12 months was 15%.
     
  • Overall survival (OS) or how long patients survived was 13 months. Estimated OS at 6 months was 78%; estimated OS at 12 months was 51%.

Limitations:

This study was designed to primarily test safety. The group of participants was small for evaluating effectiveness. The larger phase III ASCENT trial will provide larger group of participants to confirm or refute these findings and provide a direct comparison to 4 single-line therapies.

The number of participating African Americans was low; numbers of Asian and Hispanic patients were even lower. The small number of participants of varying races limits researchers’ ability to determine if there are any differences in response rates. African American women are nearly twice as likely to be diagnosed with as white women. Since African American and Hispanic women account for 10% and 18% of those with mTNBC respectively, this is a gap in information that needs to be addressed. Hopefully, as phase 3 trials enroll patients, more participants of varied racial background will participate.

Direct comparisons with other treatments for mTNBC have not yet been done. In particular, a comparison of atezolizumab plus nab-pacitaxel versus IMMU-132 would help clarify which treatment approach would work best for patients with PD-L1-positive tumors. For those with PD-L1-negative tumors, IMMU-132 may prove better than current standard of care.

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Conclusions:

This is a promising approach to treating mTNBC, particularly because there are currently few ways to treat this aggressive cancer. However, more data is needed to confirm the impact of this smart drug and to determine which, if any, of several newer treatments is best for different types of patients. The rejected a request by Immunomedic (the manufacturer of IMMU-132) for accelerated approval due to manufacturing (not clinical) concerns. An ongoing Phase III trial of IMMU-132 may provide additional data about its efficacy.

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Posted 4/162/19

References

Bardia A, Mayer IA, Vahdat LT, et al. “Sacituzumab Govitecan-hziy in refractory triple-negative breast cancer.” New England Journal of Medicine. 2019 (380):741-751. DOI:10.1056/NEJMoa1813213.

 

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