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Pathologic Complete Response to Targeted Therapy Before Surgery Linked to Better Survival for Early-Stage HER2-Positive Breast Cancer

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Women diagnosed with early-stage HER2-positive breast cancer treated with the targeted therapies Herceptin (chemical name: trastuzumab) and Tykerb (chemical name: lapatinib) before surgery who had a pathologic complete response (pCR) had better survival than women who didn’t have a pCR, according to long-term results from the NeoALTTO study.

The results were presented on Oct. 3, 2020, at the 12th European Breast Cancer Conference. Read the abstract of “Nine-year survival outcome of neoadjuvant lapatinib with trastuzumab for HER2-positive breast cancer (NeoALTTO, BIG 1-06): final analysis of a multicentre, open-label, phase 3 randomised clinical trial.”

Doctors call treatments given before surgery neoadjuvant treatments.

What is pCR?

One way doctors judge the effectiveness of neoadjuvant treatments is to look at the tissue removed during surgery to see if any actively growing cancer cells are present. If no active cancer cells are present, doctors call it a “pathologic complete response” or pCR.

Several studies have shown an association between pCR after neoadjuvant chemotherapy for breast cancer and better disease-free survival, as well as better overall survival.

Disease-free survival is how long a person lives without the breast cancer coming back. Overall survival is how long a person lives, with or without the breast cancer coming back.

About Herceptin and Tykerb

Both Herceptin and Tykerb are HER2 inhibitors used to treat HER2-positive breast cancer. Herceptin works by blocking the ability of the cancer cells to receive chemical signals that tell the cells to grow. Tykerb works inside the cancer cell by interfering with certain proteins that can cause the cancer cells to grow. Tykerb is a pill taken by mouth.

Herceptin is given intravenously, which means the medicine is delivered directly into your bloodstream through an IV or a port. A newer form of Herceptin, Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk), can be given as an injection.

About the NeoALTTO study

In the NeoALTTO study, 455 women diagnosed with early-stage or locally advanced HER2-positive breast cancer were randomly assigned to get one of three targeted therapy regimens before surgery:

  • Herceptin (149 women)
  • Tykerb (154 women)
  • Herceptin and Tykerb (152 women)

Locally advanced breast cancer is breast cancer that has spread to tissue near the breast, but not to parts of the body away from the breast.

The targeted therapies were given alone for 6 weeks, and then the women received the chemotherapy Taxol (chemical name: paclitaxel) for 12 more weeks.

After the 18 weeks of treatment were done, the women had surgery to remove the cancer. The researchers recorded how many women had a pCR to the neoadjuvant treatment.

After surgery, all the women also got three cycles of FEC chemotherapy followed by 34 weeks of the same targeted therapy regimen they got before surgery. The FEC chemotherapy regimen is made up of fluorouracil, Ellence (chemical name: epirubicin), and Cytoxan (chemical name: cyclophosphamide).

NeoALTTO results presented in 2013 after 3 years of follow-up showed that women treated with both Herceptin and Tykerb before surgery were more likely to have a pCR compared to women treated with only Herceptin or only Tykerb.

The 2013 results also showed that women who had a pCR after neoadjuvant treatment had a lower risk of the cancer coming back (recurrence), as well as better survival.

The researchers now have 9 years of follow-up data.

Overall, these long-term results show that 9-year disease-free survival rates were:

  • 63% for women treated with Tykerb alone
  • 65% for women treated with Herceptin alone
  • 69% for women treated with Tykerb and Herceptin

Nine-year overall survival rates were:

  • 77% for women treated with Tykerb alone
  • 76% for women treated with Herceptin alone
  • 80% for women treated with Tykerb and Herceptin

The researchers also compared disease-free and overall survival rates for women who had a pCR and women who did not have a pCR:

  • disease-free survival rates were 77% for women who had a pCR and 61% for women who did not have a pCR
  • overall survival rates were 88% for women who had a pCR and 72% for women who did not have a pCR

These differences were statistically significant, which means they were likely due to the difference in pCR and not just because of chance.

The link between pCR and better survival was strongest in women diagnosed with HER2-positive, hormone-receptor-negative breast cancer.

“The results from this analysis show that patients who achieve pCR are significantly more likely to survive for longer than those who do not achieve pCR,” said principal investigator Paolo Nuciforo, of Vall d’Hebron Institute of Oncology, Barcelona, in a statement. “This validates pCR as an early indicator of long-term outcome for HER2-positive disease and could help doctors decide on the best treatment. On one hand, patients not achieving a pCR may be at higher risk of recurrence, and giving extended therapy to them could potentially lower this risk. On the other hand, those patients who do achieve pCR could be spared additional … treatments.”

Herceptin and Tykerb side effects

Both Herceptin and Tykerb can cause side effects, some of them serious. Women who got the combination of Herceptin and Tykerb before surgery had about the same side effects as women who got only Tykerb. These two groups had more severe side effects than women who got only Herceptin. The most common side effects were diarrhea, liver problems, and rash. Although heart problems can be side effects of both Herceptin and Tykerb, heart problems weren’t a major side effect in the study.

What this means for you

If you’ve recently been diagnosed with early-stage HER2-positive breast cancer and will be having treatment before surgery, you may want to talk to your doctor about the NeoALTTO study and ask if treatment with Tykerb and Herceptin before surgery makes sense for you.

While having the cancer completely respond to treatment before surgery is a goal, don’t be discouraged if you don’t have a pCR. Treatments after surgery can lower your risk of breast cancer recurrence.

Armed with complete information, you and your doctor will make the best decisions for your unique situation.

Written by: Jamie DePolo, senior editor

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

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