Nick Mulcahy

December 05, 2013

The 36th Annual San Antonio Breast Cancer Symposium (SABCS) lacks an obvious headlining study, but a number of presentations, especially in the areas of metastatic and HER2-positive disease, will vie to be big topics of conversation among the thousands of attendees as they move through the 5-day meeting, which starts on December 10.

The neoadjuvant treatment of HER2-positive breast cancer is the subject of the international Neo-Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial (NeoALTTO), which is likely to receive significant attention (presentation S1-01).

Much of the curiosity about the trial, which is managed by the Breast International Group (BIG), is related to whether or not pathologic complete response (pCR) will correlate with progression-free and overall survival. "That result is anticipated to generate a lot of excitement," said symposium cochair Carlos L. Arteaga, MD, from the Vanderbilt–Ingram Comprehensive Cancer Center in Nashville, Tennessee.

Dr. Arteaga is also president-elect of the American Association for Cancer Research and, along with 2 other symposium cochairs, spoke at premeeting press briefing last month.

A proven correlation is important because pCR, which is defined as the absence of invasive cancer in the breast and lymph nodes, has not yet been demonstrated to predict longer-term breast cancer outcomes, the US Food and Drug Administration (FDA) acknowledged earlier this year. Nevertheless, in October, the FDA approved pertuzumab (Perjeta, Genentech), a neoadjuvant therapy, for the treatment of HER2-positive breast cancer on the basis of pCR results. The FDA also issued a draft guidance on the use of the measure in trials in this setting. The FDA has said that the high-risk HER2-positve breast cancer population justified the gamble of using pCR, an unproven marker, as the basis of an accelerated conditional approval of neoadjuvant treatment.

In NeoALTTO, an international team of researchers randomized women with HER2-positive primary breast cancer to lapatinib (Tykerb, GlaxoSmithKline), trastuzumab (Herceptin, Genentech), or a combination of both, followed by surgery, chemotherapy, and 1 year of the original neoadjuvant therapy.

In 2010, the investigators revealed that the combination of trastuzumab and lapatinib completely wiped out tumor cells in the breast, and thus achieved pCR, in 51.3% of women — about twice the response seen with either drug alone. The difference was statistically significant (P = .001).

Dr. Arteaga highlighted another neoadjuvant trial that looks a lot like NeoALTTO; however, the TRIO-US B07 study is only a phase 2 trial. It features a novel chemotherapy combination of docetaxel and carboplatin, in addition to lapatinib, trastuzumab, or both (presentation S1-02).

Still, the trial is important because of its neoadjuvant setting and because it, along with NeoALTTO, could affect future breast cancer drug trial designs for HER2-positive disease and the related FDA approval in this patient population, Dr. Arteaga noted.

"I think these 2 studies will contribute to the body of work, and may expand the knowledge base, that supports the notion that we can approve drugs in the neoadjuvant setting without having to do long and expensive adjuvant studies," said Dr. Arteaga.

Platinums for Triple-Negative Disease

A number of trials in hard-to-treat triple-negative disease might strengthen clinicians' decision-making in these patients, according to Kathy Miller, MD, from Indiana University in Indianapolis.

Two "important" studieswill clarify the potential role of platinum-based chemotherapy in patients with triple-negative disease, she said in a recent Medscape Miller on Oncology blog.

Adding a platinum in the neoadjuvant setting improved the pCR rate in the GeparSixto study reported this summer at the annual meeting of the American Society of Clinical Oncology. However, the trial was problematic because the anthracycline and taxane-based regimen was "nonstandard," the data were short-term, and the toxicity was "quite substantial," she said. "I think we have struggled with how to incorporate those results, and even with whether we should incorporate those results," Dr. Miller explained.

Now, at SABCS, clinicians will hear results from a phase 3 trial that randomized patients with operable stage II or III triple-negative breast cancer to standard neoadjuvant chemotherapy, standard neoadjuvant chemotherapy plus carboplatin, standard neoadjuvant chemotherapy plus bevacizumab (Avastin, Genentech), or standard neoadjuvant chemotherapy plus carboplatin and bevacizumab. Surgery then followed 4 to 8 weeks after neoadjuvant treatment (presentation S5-01).

Symposium cochair Peter Ravdin, MD, PhD, from the University of Texas Health Science Center at San Antonio, said that the trial is significant because it might show that bevacizumab has a role to play in breast cancer. The drug's "disappointing story" in breast cancer is well known, he said, referring to the drug's failure to improve survival in metastatic disease and the eventual withdrawal of FDA approval.

Additionally, there will be a presentation on a platinum-related phase 2 trial, also in the neoadjuvant setting, that randomized patients with stage II or III triple-negative breast cancer to cisplatin plus paclitaxel with or without everolimus (Afinitor, Novartis) (presentation PD1-6).

Metastatic Disease Update

Clinicians will also hear about a prospective randomized trial from India that should clarify whether or not surgery and radiation are beneficial in women with metastatic disease who respond to chemotherapy (presentation S2-02).

"The big issue is should you do anything for the tumor in the breast or not," said symposium cochair Kent Osborne, MD, from the Baylor College of Medicine in Houston. In other words, are surgery and/or radiation necessary in women with metastatic disease. Retrospective studies have suggested that surgery improves survival, he noted.

A second randomized trial from Turkey compares women with metastatic disease who received locoregional treatment for the intact primary tumor with those who did not receive such treatment (presentation S2-03).

"These 2 trials should go a long way in helping physicians" make treatment decisions in this setting, said Dr. Osborne.

Another study looks at whether or not a leukemia drug improves disease progression in metastatic disease (presentation S3-07). That drug, dasatinib (Sprycel,Bristol-Myers Squibb and Otsuka America), was added to standard antihormone therapy with letrozole in women with hormone-receptor-positive HER2-negative metastatic disease in a phase 2 trial.

Clinicians will also learn whether or not circulating tumor cells (CTCs) in the blood are a good marker for making treatment decisions in metastatic disease after first-line chemotherapy (presentation S5-07). The hope has been that CTCs will be useful in monitoring the effectiveness of chemotherapy, said Dr. Ravdin.

Screening Mammography Re-Evaluated

This year's meeting will feature a presentation that tackles one of the most contentious issues in breast cancer: the benefits and harms of screening mammography. There will be a review and re-examination of data from 4 large screening studies (presentation S1-10). The review makes the 4 disparate studies "more similar in terms of how they were analyzed," said Dr. Osborne. The analysis, led by Robert Smith, PhD, from the American Cancer Society, will include an evaluation of the phenomenon of overdiagnosis, he added.

This presentation could have an interesting counterpoint at the meeting. Cancer screening ubercritic Gilbert Welch, MD, MPH, from the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, will present a plenary lecture on screening mammography and overdiagnosis on December 11.

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