Debu Tripathy, MD
The treatment paradigm for the neoadjuvant setting of HER2-positive breast cancer continues to evolve, offering new opportunities to improve patient outcomes, according to Debu Tripathy, MD.
The addition of trastuzumab (Herceptin) to standard chemotherapy has become standard of care in both the neoadjuvant and adjuvant setting, but other agents, such as pertuzumab (Perjeta), have been shown to demonstrate an increase in the complete pathologic response rate (pCR) beyond that which is seen with trastuzumab and chemotherapy alone.
“Pertuzumab, which showed a larger increase of pCR, was also shown in other trials to have improved survival in the metastatic setting on all bases of that data—not only the neoadjuvant data, but the long-term data in metastatic disease,” said Tripathy.
In an interview with OncLive
at the 2017 Miami Breast Cancer Conference
(MBCC), Tripathy, a professor and chairman in the Department of Breast Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed current and emerging treatment strategies in the neoadjuvant setting for patients with HER2-postive breast cancer.
OncLive: Please provide an update on neoadjuvant treatment strategies in HER2-positive breast cancer.
The use of neoadjuvant therapy for HER2-positive breast cancer is an area of increasing understanding, knowledge, and interest. We know that patients clearly achieve a higher chance of a pCR with the addition of trastuzumab to standard chemotherapy. This occurs in both the neoadjuvant and adjuvant settings, which had led to it being the standard of care.
We also know that patients who achieve a pCR tend to have a better disease-free survival, particularly those patients who are HR-negative. We have begun to use this platform to test new drugs. Lapatinib (Tykerb) and pertuzumab were 2 drugs that had been tested in large scale trials and both drugs increase the pCR beyond that which is seen with trastuzumab and chemotherapy alone.
Pertuzumab, which showed a larger increase in pCR, was also shown in other trials to have improved survival in the metastatic setting on all bases of that data—not only the neoadjuvant data but the long-term data in metastatic disease. The FDA approved pertuzumab in the neoadjuvant setting using a new pathway that they had developed over the past few years. That was contingent upon an adequately powered adjuvant trial showing an improvement in the disease-free survival. Nevertheless, that accelerated FDA approval of pertuzumab has now made it the standard of care because it improves the pCR.
The NeoSphere trial, which looked at docetaxel with either trastuzumab or trastuzumab plus pertuzumab followed by FEC (fluorouracil, epirubicin, and cyclophosphamide). The pertuzumab combination arm showed a higher pCR rate.
The TRYPHAENA trial showed pertuzumab in 3 different arms: [The first arm received pertuzumab, trastuzumab, and FEC, followed by pertuzumab, trastuzumab, and docetaxel; the second arm received FEC, followed by pertuzumab, trastuzumab, and docetaxel; and the third arm received pertuzumab, trastuzumab, docetaxel, and carboplatin. pCR was similar in all 3 arms.]
Those 2 trials together laid the foundation for either anthracycline or nonanthracycline containing a pertuzumab therapy.
What are the advantages to the patients? Presumably, the additional downstaging may further increase the number of patients that can have a breast-conserving surgery.
I believe this has helped us understand which therapies improve pCR and which of those may have an impact on disease-free survival.