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Adding Carboplatin to Chemotherapy Before Surgery Improves Early-Stage Triple-Negative Breast Cancer Outcomes

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Adding carboplatin (brand name: Paraplatin) to the standard neoadjuvant chemotherapy regimen for early-stage triple-negative breast cancer improved event-free survival, according to a study.

The study also found that adding veliparib to standard neoadjuvant chemotherapy had no effect on outcomes.

The research was presented on Sept. 17, 2021, at the European Society for Medical Oncology (ESMO) Congress 2021. Read the abstract of “Event-free survival (EFS), overall survival (OS), and safety of adding veliparib (V) plus carboplatin (Cb) or carboplatin alone to neoadjuvant chemotherapy in triple-negative (TNBC) after ≥4 years of follow-up: BrighTNess, a randomized phase III trial.”

Doctors call treatments given before surgery neoadjuvant treatments. So doctors call chemotherapy given before surgery neoadjuvant chemotherapy.

For this study, event-free survival means the length of time a person lived without:

  • the cancer growing
  • the cancer coming back in the same breast or anywhere else in the body
  • receiving a second primary cancer diagnosis

About triple-negative breast cancer
About carboplatin
About veliparib
About the study
What this means for you

About triple-negative breast cancer

Triple-negative breast cancer is:

  • estrogen-receptor-negative
  • progesterone-receptor-negative
  • HER2-negative

Triple-negative breast cancers are usually more aggressive, harder to treat, and more likely to come back (recur) than cancers that are hormone-receptor-positive or HER2-positive. Triple-negative breast cancers don’t usually respond to hormonal therapy medicines or medicines that target the HER2 protein.

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About carboplatin

Carboplatin is the only platinum-based chemotherapy medicine approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer. Platinum-based chemotherapy weakens or destroys breast cancer cells by damaging the genetic material in the cells and making it hard for cells to repair any genetic damage.

Other studies have shown that adding carboplatin to the standard neoadjuvant chemotherapy regimen of Taxol (chemical name: paclitaxel) — followed by Adriamycin (chemical name: doxorubicin) and Cytoxan (chemical name: cyclophosphamide) — for early-stage triple-negative breast cancer improves pathologic complete response (pCR).

One way doctors judge the effectiveness of neoadjuvant treatments is by looking for any actively growing cancer cells in tissue removed during surgery. If there aren’t any active cancer cells in the tissue, doctors call it a “pathologic complete response” or pCR.

Still, the earlier studies weren’t designed to see if adding carboplatin improved long-term outcomes. And since carboplatin can increase the risk for certain blood cancers — such as myelodysplastic syndrome and leukemia — it hasn’t been clear if the benefits of adding carboplatin outweigh any risks.

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About veliparib

Experimental veliparib is a type of medicine called a PARP inhibitor. The PARP enzyme fixes DNA damage in both healthy cells and cancer cells. PARP inhibitors have been shown to work against breast cancer with a BRCA1 or BRCA2 mutation by making it very difficult for these cancer cells to fix DNA damage.

Right now, two PARP inhibitors have FDA approval to treat metastatic HER2-negative breast cancer with a BRCA1 or BRCA2 mutation:

  • Lynparza (chemical name: olaparib)
  • Talzenna (chemical name: talazoparib)

The FDA has not approved veliparib to treat breast cancer.

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About the study

Called BrighTNess, this study wanted to see if adding carboplatin and veliparib, or carboplatin alone, to standard chemotherapy before surgery for early-stage triple-negative breast cancer would improve outcomes, including pCR, event-free survival, and overall survival.

Overall survival is how long people live, whether or not the cancer grows or comes back.

Between April 4, 2014 and March 18, 2016, researchers randomly assigned 634 women diagnosed with stage II or stage III triple-negative breast cancer to one of three neoadjuvant treatment regimens:

  • 316 women received Taxol, carboplatin, and veliparib
  • 160 women received Taxol and carboplatin
  • 158 received Taxol alone

All the women then received four cycles of Adriamycin and Cytoxan.

After neoadjuvant chemotherapy was complete, the women had surgery to remove the breast cancer.

The BrighTNess study’s 2018 results showed that adding carboplatin to neoadjuvant chemotherapy improved pCR, but adding veliparib had no effect.

This latest analysis looked at survival rates and second cancer diagnoses after about 4.5 years of follow-up.

The results showed that adding carboplatin to the standard chemotherapy regimen improved event-free survival by about 11%. Event-free survival rates were:

  • 78.2% for women treated with Taxol, carboplatin, and veliparib
  • 79.3% for women treated with Taxol and carboplatin
  • 68.5% for women treated with Taxol alone

This difference was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.

The researchers noted that women with pCR after surgery had better event-free survival than women without pCR after surgery.

Again, the results showed that adding veliparib had no effect on outcomes.

While women in the Taxol and carboplatin treatment group had better overall survival than women in the other two treatment groups, this difference was not statistically significant, which means that it could have been due to chance and not because of the difference in treatment.

The researchers found that adding carboplatin to the chemotherapy regimen caused more blood-related side effects, including:

  • anemia, or low red blood cell counts
  • neutropenia, or low white blood cell counts
  • pancytopenia, or low levels of red blood cells, white blood cells, and platelets

Still, the researchers reported these side effects didn’t affect the survival results and that carboplatin didn’t increase the risk of other cancers, such as myelodysplastic syndrome and leukemia.

“These findings support the inclusion of carboplatin in neoadjuvant chemotherapy for stage II to III triple-negative breast cancer,” said Sibylle Loibl, M.D., Ph.D., chair of the German Breast Group and professor of medicine at the University of Frankfurt, who presented the results.

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What this means for you

If you’ve been diagnosed with early-stage triple-negative breast cancer, these results are very encouraging. Doctors have been looking for more clarity on whether the benefits of adding carboplatin to the standard neoadjuvant chemotherapy regimen for early-stage triple-negative breast cancer outweigh the risks. This study’s results strongly suggest carboplatin offers more benefits than risks.

No matter which treatments your doctors recommends for you, you may want to ask about:

  • the reasons each treatment is recommended (including any combinations)
  • the treatment timing and sequence
  • the expected benefits, risks, and side effects of each treatment

If your doctor recommends neoadjuvant chemotherapy for you and carboplatin isn’t part of the regimen, you may want to bring up this study. You also may want to ask your doctor to recommend clinical trials with carboplatin that make sense for your unique situation.

Visit Triple-Negative Breast Cancer for more information.

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Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser

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