'Major Finding' in Triple-Negative Breast Cancer

Effective Drug for Difficult Tumor Is Already on Pharmacy Shelf

Nick Mulcahy

December 12, 2019

SAN ANTONIO — Triple-negative breast cancer (TNBC) is so called because its tumors lack three common receptors known to fuel tumor growth — estrogen, progesterone, and HER2/neu. These biological targets allow many breast tumors to be "druggable" with potentially curative therapies such as tamoxifen and trastuzumab. TNBC is lamented — and feared — because of its paucity of effective treatment options.

Now German investigators indicate that the chemotherapy drug capecitabine impacts this difficult-to-treat breast cancer in early stage disease.

Capecitabine improves both disease-free and overall survival (DFS and OS) when used as an add-on to other standard chemotherapy, either before or after surgery, reported Marion van Mackelenbergh, MD, of the University of Kiel, Germany, and colleagues here at the San Antonio Breast Cancer Symposium 2019.

Capecitabine's efficacy had been hinted at in single studies but only fully surfaced via the German team's new meta-analysis of 12 clinical trials involving more than 15,000 patients, said Priyanka Sharma, MD, University of Kansas Medical Center, Westwood, Kansas, who acted as meeting discussant of the study.

The meta-analysis showed that adding capecitabine to standard chemotherapy in TNBC improves DFS by 18% (hazard ratio [HR], 0.82; P = 0.004) and OS by 22% (HR, 0.78; P = 0.004).

It's a "MAJOR FINDING," tweeted meeting attendee Harold Burstein, MD, Dana-Farber Cancer Institute, Boston (@DrHBurstein). "We have undervalued this approach because all-comers trials rarely showed a benefit."

The new study is "big news for #TNBC #SABCS19," posted Burstein, who is known for measured comments about breast cancer research and treatment.

Capecitabine is an oral fluoropyrimidine, which are inactive prodrugs of cytotoxic 5-FU that are absorbed through the gastrointestinal mucosa and converted to 5-FU by enzymes. Capecitabine is approved for use as monotherapy or in combination with docetaxel in metastatic breast cancer.

The new results address usage in early breast cancer.

The results provide evidence to support some current guidelines, observed Sharma. The National Comprehensive Cancer Network and St Gallen guidelines both say that clinicians should "consider adjuvant capecitabine in the setting of residual disease following neoadjuvant taxane/alkylator and anthracycline chemotherapy," she said.

Such choices mean that only early breast cancer patients at highest risk (ie, still have lingering disease after initial chemo) will be exposed to the additional toxicity of capecitabine, Sharma added, in advising about practical application of the new findings.

The new meta-analysis fills a void, said the researchers.

"Despite the large number of patients with early breast cancer that have been treated with capecitabine in randomized trials no individual patient data meta-analysis has yet been conducted," the team wrote in their meeting abstract.

To do so, the German investigators searched for completed randomized trials involving use of capecitabine in early breast cancer as adjuvant or neoadjuvant therapy and having at least 100 patients.

Individual data from 15,457 patients was collected, including 7980 who received capecitabine during the course of their treatment and 7477 patients who were treated in control arms. Median age at diagnosis was 54 years in both groups. Most patients had stage 2 tumors (55.9%) at diagnosis and the majority presented with nodal involvement (74.0%). Estrogen and progesterone receptor positivity was observed in 66.0% and 56.9%, respectively, and 15.1% of patients were diagnosed as HER2-positive. In sum, 2816 patients (18.2%) received neoadjuvant treatment and 12,641 (81.8%) an adjuvant chemotherapy regimen.

Notably, there was also no effect on DFS if studies (n = 5) were selected in which capecitabine was given instead of another drug. Thus, seven studies, in which capecitabine was given in addition to standard chemo, remained and those showed the above-referenced results.

Sharma has multiple financial ties to pharmaceutical companies. Burstein has disclosed no relevant financial relationships.

San Antonio Breast Cancer Symposium 2019: Abstract GS1-07. Presented December 11, 2019.

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