Tiffany A. Traina, MD
The treatment landscape of HER2-postive breast cancer went through an exponential shift in 2017 with 2 new FDA approvals and the emergence of encouraging novel therapeutic options.
In July 2017, the FDA approved neratinib (Nerlynx) for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer following postoperative trastuzumab (Herceptin). The approval followed a 12-4 recommendation from the agency’s Oncologic Drugs Advisory Committee, stemming from the results of the phase III ExteNET trial. Even though the drug is approved, many clinicians are hesitant to adopt it, due in part to the success observed with adjuvant therapy with pertuzumab (Perjeta).
The approval for pertuzumab in combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with HER2-positive early breast cancer came in December 2017. This regimen is indicated for those at high risk for recurrence, and is based on findings from the APHINITY trial. Results from that phase III trial reported that this regimen demonstrated a 3-year invasive disease-free survival rate of 94.1% versus 93.2% for those who received trastuzumab plus chemotherapy and placebo.
Considering this indication for pertuzumab, experts such as Tiffany A. Traina, MD, say that they are unsure of where to place neratinib in the sequence of treatment. This hesitancy is due in part to the early trials of neratinib, which did not include patients who had prior exposure to pertuzumab, Traina explained.
Other agents in the pipeline include DS-8201, which Traina believes will fit well into the HER2-positive landscape if approved, as it is both well tolerated and highly effective.
In an interview with OncLive
, Traina, a medical oncologist at Memorial Sloan Kettering Cancer Center, discussed her experiences with using neratinib and pertuzumab, and shared her excitement on the direction in which the HER2-positive breast cancer field is moving.
OncLive: Can you discuss the trepidation that we are seeing with neratinib?
Neratinib’s approval is for an extended adjuvant scenario for HER2-positive early-stage breast cancer. It’s in a unique position because so much has evolved in the treatment of HER2-positive early-stage disease. We now have much more use of neoadjuvant pertuzumab in combination with trastuzumab and an anthracycline-taxane–based neoadjuvant regimen. We recently saw the data from the APHINITY trial showing that 1 full year of adjuvant trastuzumab and pertuzumab was associated with improved survival outcomes. Now trying to integrate the FDA approval of neratinib is just a bit more challenging. The early trials with neratinib did not have patients who had prior exposure to pertuzumab. Therefore, I am not quite sure where its place will be.
I know there is a lot of debate and discussion of whether patients who receive preoperative pertuzumab and fail to have a pathologic complete response should continue on their pertuzumab, which is supported by the APHINITY trial. That might be a place for trying neratinib where it may not be cross-resistant, but it is a big unknown. I don't think the European Union’s decision is going to impact the US provider's use of neratinib—it’s just more of matter of the clinical trial data not guiding what current practice really is.
How would you go about determining treatment for early-stage HER2-positive breast cancer?
In practice, I favor using pertuzumab in patients who have tumors larger than 2 cm in the setting of node-negative or node-positive disease. I do still incorporate a bit of neoadjuvant therapy, so anthracycline-taxane–based trastuzumab and pertuzumab and then, following surgery, continuing the trastuzumab and pertuzumab for a full year. For tumors that are smaller than 2 cm and are node-negative, we can de-escalate treatment. As opposed to incorporating pertuzumab, regimens supported by Dr Sara Tolaney's work showed that weekly paclitaxel for 12 weeks with trastuzumab may be sufficient.