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Tailored Treatment Based on Response to Early Chemotherapy May Improve Survival in Early-Stage Disease

Long-term results of GeparTrio trial show greatest survival benefit in those with hormone-positive tumors

February 18, 2014

Written By Nicole Katze, MA, Editor and Manager, Publications
Reviewed By Lee Gravatt Wilke, MD, FACS

Researchers who observed whether a tumor shrank after the first few cycles of pre-surgery, or neoadjuvant, chemotherapy made an important observation. They found that when they based further chemotherapy treatment on the tumor’s reaction, outcomes were best for women with hormone receptor-positive breast cancer. These women lived for the longest spans of time without the cancer growing or traveling, compared with women with tumors testing negative for hormones.  

Among women with tumors testing negative for hormones, if the tumor was completely removed by chemotherapy, they lived longer than women with tumor remaining in the breast or lymph nodes.  Changing the chemotherapy based on response did not improve their survival as it did for the women with hormone-positive cancers.  

These long-term findings from phase III of the GeparTrio trial may lead to more individualized treatment based on breast cancer type in the future. They also support the use of neoadjuvant chemotherapy.

Background

Chemotherapy can be given before or after surgery to help kill cancer cells that might remain in the breast or other tissues. Yet, some doctors believe that neoadjuvant chemotherapy may help improve survival.

If you have a very large tumor, neoadjuvant chemotherapy may help shrink it, making it easier to perform breast conservation surgery, also called lumpectomy. Though the use of chemotherapy before surgery has been studied in clinical trials for other uses, doctors do not yet know if giving it before or after surgery is best for survival.

The GeparTrio Study

Findings from past studies suggest knowing whether a tumor responds to initial chemotherapy medicines may help doctors identify which treatments will work best for the rest of a person’s pre-surgery treatment. When chemotherapy is used in this way it is called response-guided neoadjuvant chemotherapy, because your doctor lets what happens during your first rounds of chemo guide what other chemotherapy medicines you will be given before your surgery.

The GeparTrio trial followed participants for an average of 5 years and found that pathologic complete response (pCR) rates were not different in patients who “switched” or changed chemotherapy based on an initial response or nonresponse to therapy. These 5-year findings were reported in the Journal of the National Cancer Institute in 2008.

Long-term Goals

The primary goal of the GeparTrio trial was to assess rates of pCR after response-guided neoadjuvant chemotherapy. Yet, the researchers continued to analyze the study data for 5 years to see if a tumor’s response to early chemotherapy helped improve survival in the long-term.

To do this, they evaluated:

  • disease-free survival (DFS), the time from the start of treatment to the cancer growing or traveling, or death from any cause

and

  • overall survival (OS), the time from the start of treatment to death from any cause. 

Design

A total of 2,012 participants with a breast cancer which had not already been treated took part in the trial. The participants also each had at least one factor that qualified them as high-risk and made them candidates for neoadjuvant therapy.

Those who took part in the study were given two cycles of TAC chemotherapy on day 1, every 3 weeks. TAC is:

  • Docetaxel (Taxotere)
  • Doxorubicin (Adriamycin)
  • Cyclophosphamide (Cytoxan)

After these initial cycles, tumor size was measured by ultrasound. The participants were then divided into two groups: Those whose tumors shrank with TAC (responders), and those whose tumors did not shrink (nonresponders).

For their further rounds of chemotherapy, the 1,309 responders were randomly assigned to:

  • continue TAC for 4 more cycles

or

  • continue TAC for 6 more cycles

The 622 nonresponders were randomly assigned to:

  • continue TAC for 4 more cycles

or

  • receive 4 cycles of NX chemotherapy, which is vinorelbine (Navelbine) on days 1 and 8, plus capecitabine (Xeloda) taken as a pill twice a day on days 1 though 14, every 3 weeks

Tumor size was measured again using ultrasound, mammogram and touch, after the final round of treatment. All participants then had surgery within 21 days of completing neoadjuvant chemotherapy.

Long-term Results

The trial team found that women who continued the same chemotherapy if they were a responder and switched chemotherapy if they were a nonresponder had an improvement in their DFS. The women that benefitted the most from this switch were those with hormone-positive tumors. Further studies are needed to confirm this finding.

They also found:

  • Overall, the pCR rate did not help doctors predict whether response-guided chemotherapy would benefit a participant
  • OS was somewhat longer in responders than nonresponders, and hormone-positive tumors showed a trend toward longer DFS after response-guided neoadjuvant chemotherapy than hormone-negative tumors. The investigators noted that the 5-year follow up may not have been long enough to show true OS effects.

What This Means for You

If you are newly diagnosed with “high-risk” breast cancer – cancer with a tumor over 2 cm, high tumor grade, estrogen receptor-negative disease or cancer in the lymph nodes – and are working with your healthcare team on a treatment plan, consider talking with your doctors about whether neoadjuvant chemotherapy will be used.

Though the role of response-guided neoadjuvant chemotherapy is still being researched, studies like the GeparTrio trial are expanding knowledge on the topic. In time, using tumor response to adjust chemotherapy treatment or predict survival may help doctors more accurately personalize breast cancer treatments.

If you’re interested in neoadjuvant chemotherapy, ask your team about clinical trials that may give you access to newer treatment techniques.

To learn more about breast cancer and making treatment decisions, read our Guide for the Newly Diagnosed and Guide to Understanding Treatment Decisions, available on lbbc.org.

von Minckwitz, G, Blohmer, J, Costa, S, Denkert, C, Eidtmann, H, Eiermann, W, et al. Response-guided neoadjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. 2013; 31 (29): 3623-3630 

Denver, CO  ·  September 13, 2014

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