Neoadjuvant Therapy Improves Breast Conservation Outlook

Debu Tripathy, MD

By exploring different neoadjuvant treatment options, physicians may be able to reduce tumor size and thereby downstage certain patients who have HER2-positive breast cancer, making it possible for less extensive surgery and fewer long-term complications, according to Debu Tripathy, MD, chair of the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston. Tripathy provided an update on neoadjuvant strategies in HER2-positive breast cancer at the 2017 Miami Breast Cancer Conference.

“With the preoperative management of patients with HER2-positive breast cancer, there’s been an increasing trend over the last few years to identify patients who could be downstaged by receiving their systemic therapy first before surgery,” Tripathy said. “We’re finding that this allows more patients to be able to undergo breast conserving surgery, and, in some cases, less axillary surgery. Patients may be candidates for sentinel node-only surgery even though a full dissection may have been indicated at initial presentation.”

This means not only less invasive surgery and quicker recovery for these patients, but also a diminished chance of developing long-term complications, such as postmastectomy pain and lymphedema, Tripathy said.

Tripathy recommends that neoadjuvant therapy be given to patients with HER2-positive breast cancer who, at the time of clinical staging, are stage II or higher. The current standard of care for this patient population is preoperative chemotherapy with pertuzumab (Perjeta). The option with the most data behind it is the 4-drug combination of docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab. Other regimens are being used, too. Tripathy cited anthracycline therapy followed by taxane therapy with trastuzumab and pertuzumab added. This subgroup of patients typically is very responsive to systemic therapies of chemotherapy combined with an anti-HER2 therapy, he said.

“In the last few years, the addition of pertuzumab to trastuzumab—using dual antibody therapy—has improved the complete pathologic response rate and trials are still pending to see whether this treatment may also lower the risk of recurrence and, ultimately, lower the risk of death,” Tripathy said. “But at this point, we do know that [these drugs] offer better downstaging, so we will be discussing how to approach these patients with HER2-positive cancers, which regimens to use, and what to expect in terms of downstaging.”

Some patients with HER2-postive breast cancer may be better off skipping neoadjuvant therapy, Tripathy explained. “For patients who are less than stage II, at least in clinical exams and imaging before surgery, we advise those patients to get the surgery first, because for patients who end up having stage I cancer, they may be able to get away with less-intense systemic therapy,” he said.

For these stage I patients, Tripathy currently uses a regimen with fewer short-term and long-term toxicities. This regimen has been shown to provide an excellent control rate—less than 2% of patients had recurrence in a published trial. The plan consists of weekly paclitaxel for 12 treatments along with trastuzumab, and then trastuzumab every 3 weeks for 40 weeks.

If at the time of surgery, first the patient is upstaged to stage II or III, for example, when cancer is unexpectedly found in the lymph nodes, then the patient can still be treated with pertuzumab-containing therapy, Tripathy said. However, in this instance the treatment is not being used to downstage the tumor. Instead, it is being used with the hope that pertuzumab may provide long-term benefit by lowering the recurrence

rate. This theory has not yet been proved, but is being looked at in the large, ongoing APHINITY trial, which is comparing standard adjuvant anthracycline or nonanthracycline therapy and trastuzumab with or without pertuzumab. The trial has completed accrual, but results are not yet published. There are also additional neoadjuvant regimens that are being investigated for patients with HER2-positive breast cancer, such as the immunoconjugate T-DM1 (trastuzumab emtansine; Kadcyla) or docetaxel, carboplatin, trastuzumab, and pertuzumab with immunotherapy.

“NCCN guidelines do give you the option to add postoperative pertuzumab, with the thinking that there is such a high chance that the APHINITY study will be positive that they didn’t want patients not to be able to avail themselves [of it],” Tripathy said. “We feel that these patients should at least be considered and have that treatment option be discussed with them because the NCCN guidelines do provide for that, even in the postoperative setting, given its strong safety record and the known improvement in survival seen in the metastatic setting. That’s a nuance that we want to make sure physicians are aware of.”

He also discussed studies that looked at serial tissue biopsies in patients receiving HER2 therapy. These trials include: KRISTINE, PERTAIN, NSAP B-52, and CLEOPATRA.

“Neoadjuvant therapy offers not only better treatment for patients but a great research platform,” Tripathy said. “We’ll review some of the clinical trials that are going on in this area, including some of the new immunotherapy trials that are being tested in the neoadjuvant setting as well, and then we’ll review the current and evolving standards of care in this population of patients.”

Tripathy said that he does not believe immunotherapy drugs will be approved in this setting any time soon, because currently only phase I and phase II studies are reporting data. However, immunotherapy agents will become available in the clinical trial setting, and larger scale randomized trials are getting underway, he said.

“In order for this field to move forward quickly, we do want to make sure that patients who might be eligible and are interested are referred for clinical trials. That’s why, at this conference, we place an emphasis on letting our

audience know what clinical trials are open and whether any of our audience members are participating in these clinical trials or have them open in their centers,” Tripathy said. “We want to make sure that these trials are available for patients, not only for their own benefit but also to help the research area advance and make sure we maximize the success and timeliness of these clinical trials.”