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Comparing Treatments in Breast Cancer Subsets

Sibylle Loibl, M.D., Ph.D., discusses the GeparSepto trial and what it means for women with breast cancer. 
BY Greg Kennelty
PUBLISHED January 05, 2017
Abraxane (nab-paclitaxel) is more beneficial than Taxol (paclitaxel) in some patients with breast cancer, as seen in the GeparSepto trial, says Sibylle Loibl, M.D., Ph.D.
In an interview with CURE, Loibl, co-chair of the German Breast Group (GBG) and associate professor at the University of Frankfurt, discusses the most recent subanalysis of the GeparSepto trial, how the drugs match up in terms of toxicities, and a separate set of data looking at patients with breast cancer who are also pregnant.

Can you tell us a little about the subanalysis of the GeparSepto trial?

The GeparSepto study was investigating if the exchange of Abraxane instead of paclitaxel followed in both arms by Ellence (epirubicin) would lead to an increased pathological complete remission (PCR) rate. This could be demonstrated overall, but we were curious to see how that would play out in the subgroups of luminal patients, triple negative breast cancer patients and HER2-positive with or without hormone receptor (HR) expression. The patients with HER2-positive disease received, in an addition to the chemotherapy, Perjeta (pertuzumab) plus Herceptin (trastuzumab) from the very beginning for the whole 24 weeks and continued afterward with Herceptin for up to one year.
We have seen that in the HER2-positive cohort, the PCR rate was much higher. We achieved a PCR rate of almost 75 percent in the HR-negative HER2-positive cohort. There was a difference in favor of Abraxane, but it was not statistically significant. In that group, the HER2 treatment is probably more important than the chemotherapy schedule. What we also found, and this has already ben seen in previous studies, is that the definition of the PCR is more important in the HER2-positive cohort than the triple negative cohort.
The second results were about the toxicity, because there have not been so many data in the neoadjuvant setting using the two antibodies. In fact, this is the largest cohort using the two antibodies in the neoadjuvant setting and using 24 chemotherapy regimen. In TRYPHAENA, the chemotherapy was 18 weeks. We found the PCR rates were comparable to that of the TRYPHAENA trial when Perjeta was added to Herceptin, and the toxicity was also comparable to that. Especially the rate of diarrhea is to be noted, so up to 10 percent of the patients had greater than grade 2 diarrhea, which seems to be noteworthy.

Are there any next steps or other analyses of this trial that are important?

We're currently conducting the rate of peripheral sensory neuropathy, and how that has evolved after patients have completed their treatment. We have seen a higher rate with peripheral sensory neuropathy with paclitaxel compared to Abraxane, but we can also see that the neuropathy is decreasing around one year after the treatment, and the rate then of grades 2 and higher is equivalent between paclitaxel and Abraxane. Grade 3 and 4 is a little more tricky because the neuropathy stays a little longer.
At the moment the neuropathy fades away. There have been several studies investigating ameliorating treatment and supportive treatment, but so far neither has really been proven to be helpful to prevent or treat it.

What do you really want the oncology community to take away from this analysis?

What we have seen in the GeparSepto study is the greatest benefit of using Abraxane instead of paclitaxel was actually in the triple negative cohort, where we could almost double the PCR rate. This is a very important message because these are the patients currently treated with chemotherapy, and therefore you need to use the best chemotherapy that you have. it is less critical in the luminal and HER2-positive type. So we would like oncologists to take this message in the triple negative population and use nab instead of paclitaxel, and monitor the periphery sensory neuropathy carefully.

Do you think there will be a point where we combine Abraxane with other agents?

Probably the most interesting combination so far are the checkpoint inhibitors, which there are trials investigating. There are also data combining Abraxane with carboplatin in the firstline setting and the metastatic setting, though there's a trial looking specifically into this combination. These are the two main combinations currently being investigated in triple negative breast cancer.

Can you tell us a little about your collection of data from pregnant patients with breast cancer?

We have, since 2003, a registry ongoing collecting patients diagnosed with breast cancer during pregnancy. In parallel, we are also collecting data from patients who are very young with breast cancer, meaning diagnosed below the age of 40, as a control cohort. We collected tissue as well from our pregnant breast cancer patients, and we investigated if there is a different mutation pattern in the pregnant breast cancer patients compared to data which we retrieved from already collected data set.
In essence, we found the main driver is probably the different cohorts. The pregnant breast cancer cohort was younger, and there were less HR-positive patients in this cohort compared to the TCHA dataset after matching the numbers, although this is the largest pregnant breast cancer cohort investigating somatic mutations in breast cancer. We also found that we have higher amounts of TP53 mutations in the pregnant and less PI3 kinase mutations, which could possibly explain the slight imbalances in the baseline characteristics.

What kind of clinical implications can this data have?

We cannot derive any clinical conclusions from that. There was the rumor that patients diagnosed with breast cancer during pregnancy have worse outcomes due to the underlying biology. So far in the large dataset from our cohort of almost 500 patients and 800 controls, we could not demonstrate that the pregnant patients had a worse outcome. The worse outcome some other investigations have shown is mainly driven by the non-standard treatment of those patients. We wanted to see if we can see some biological differences by investigating the mutations in this cohort.
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