Tracks 1-14

Track 1 NSABP/CIRG BETH trial: Adjuvant chemotherapy/trastuzumab with or without bevacizumab in HER2-positive BC Track 2 Potential mechanisms of action of bevacizumab Track 3 Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) study Track 4 Ongoing and recently reported studies of neoadjuvant chemotherapy with trastuzumab in early BC Track 5 NSABP-B-45: Adjuvant sunitinib in patients with residual invasive BC after neoadjuvant chemotherapy Track 6 Viewpoint on the recently reported NSABP-B-30 and BCIRG 005 adjuvant study results Track 7 Prospective evaluation of amenorrhea and clinical outcomes among premenopausal women treated on NSABP-B-30 Track 8 Role of adjuvant ovarian ablation/ suppression for premenopausal patients with early BC Track 9 Clinical use of the Oncotype DX assay for postmenopausal patients with ER/PR-positive, node-positive early BC Track 10 Utility of Oncotype DX in the neoadjuvant setting Track 11 Mastectomy for local control in patients with synchronous primary and metastatic BC Track 12 CLEOPATRA: Trastuzumab/ docetaxel with or without pertuzumab in previously untreated HER2-positive mBC Track 13 Proposed evaluation of chemotherapy/trastuzumab for patients with HER2-low early BC Track 14 Improved recurrence-free survival with the incorporation of capecitabine into adjuvant therapy in the FinXX trial

Select Excerpts from the Interview

Track 1

DR LOVE: Would you discuss the recently opened NSABP/CIRG collaborative BETH adjuvant trial for patients with HER2-positive breast cancer?

DR SWAIN: The NSABP has joined with the CIRG to conduct a large adjuvant study for patients with HER2-positive disease. The BETH study is based on Dennis Slamon and Mark Pegram’s preclinical data, the Phase I and Phase II study combining trastuzumab with bevacizumab (Pegram 2006) and the BCIRG 006 study using docetaxel, carboplatin and trastuzumab (TCH; [Slamon 2006]).

The BETH study is open to almost every patient with HER2-positive disease, even those with node-negative disease. Patients will be randomly assigned to TCH with or without bevacizumab (3.1).

DR LOVE: What’s the biologic and clinical rationale for this trial?

DR SWAIN: Dennis Slamon examined approximately 600 tumors and showed that those that were HER2-positive and had a high VEGF expression had a worse prognosis (Konecny 2004). After showing synergy with the combination of trastuzumab and bevacizumab in preclinical studies, he evaluated the combination in a Phase II study of HER2-positive advanced breast cancer and the overall response rate was approximately 50 percent (Pegram 2006). So it’s nicely going from the bench to the bedside, as Dr Slamon did with the BCIRG 006 study (Slamon 2006).

DR LOVE: What do we know about the safety of combining trastuzumab and bevacizumab?

DR SWAIN: In the Phase II study 13 patients had a decrease in ejection fraction (EF), with one severe heart failure. Most of these decreases in EF were Grade I and were not something you would act on. However, hypertension is a known toxicity of bevacizumab, and with a big afterload we may see more cardiac toxicity in combination with trastuzumab. Denise Yardley in the Sarah Cannon Group presented at San Antonio three different parallel studies evaluating bevacizumab in combination with docetaxel regimens — TAC, AC T or TCH — to study the cardiac toxicity (Yardley 2008; [3.2]). One heart failure occurred in the study of TCH with bevacizumab, three in the TAC group and three in patients who received AC T. In the BETH study, we are carefully monitoring EF and are conducting a cardiac analysis of several hundred patients, similar to the B-31 study and the N9831 study, to make sure no excessive cardiac toxicity is incurred.

Track 14

DR LOVE: Would you discuss the FinXX study evaluating the addition of capecitabine to a taxane/anthracycline base regimen?

DR SWAIN: In this trial, patients were randomly assigned to treatment with three cycles of docetaxel (T) cyclophosphamide, epirubicin and 5-fluorouracil (CEF) or docetaxel and capecitabine (XT) cyclophosphamide, epirubicin and capecitabine (CEX; [Joensuu 2008]). It included 1,500 patients with node-positive disease and node-negative tumors.

The results were striking (3.3). Recurrence-free survival was significantly better in the XT CEX group. It’s definitely a positive trial. They found 80 events in the T CEF arm and 54 events in the capecitabine arm. You can’t argue with it. The distant events were 72 versus 42. It appeared to be active.

The design of the FinXX trial was excellent. It was based on previous studies using docetaxel/capecitabine (O’Shaughnessy 2002), so it makes sense that it’s beneficial, but it’s not enough for me to change my treatment approach now. However, it makes me think about it, and I am anxious to see data from Joyce O’Shaughnessy and the US Oncology trial evaluating AC T versus AC XT.

The other point is that evaluating adverse events is where we’re headed with the chemotherapy trials. We want the fewest adverse events possible. In the FinXX trial, the TX CEX arm resulted in less toxicity. Of all the different toxicities, the febrile neutropenia and the myalgias were more prominent in the group that did not receive capecitabine. So I believe that it could be something people will want to use in the future.

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Neil Love, MD

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Edith A Perez, MD
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Sandra M Swain, MD
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