Welcome to the first edition of OncoFacts for 2010. As in past years, we will be reporting relevant and breaking issues on a monthly basis. In this issue, I will be highlighting abstracts that were released in December at the 2009 San Antonio Breast Cancer Symposium.

Trastuzumab in the Adjuvant Setting

Two of the previously reported adjuvant trastuzumab trials were updated at this meeting with new findings and more mature data.

Perez et al presented an update of the NCCTG N9831 trial of chemotherapy alone, with the sequential or concurrent addition of 52 weeks of trastuzumab in the adjuvant setting. The original trial randomized 3505 women with HER-2-positive early breast cancer to doxorubicin and cyclophosphamide (AC) → weekly paclitaxel (T), versus AC→ weekly paclitaxel → trastuzumab (H [52 weeks]), versus AC→ weekly paclitaxel + concurrent trastuzumab → trastuzumab to complete 1 year of therapy. What has been presented previously has been the comparison of the non-trastuzumab arm to the concurrent paclitaxel + trastuzumab arms. This presentation centers on the arm that gives the trastuzumab in sequence to the chemotherapy.

Results: At a median follow-up of 5.5 years, the 5-year DFS for AC→T versus AC→T →H is 72% versus 80% with a HR of 0.70. The 5-year DFS for AC→T→H versus AC →T/H→ H was 80% versus 84% with a HR of 0.77 and a P-value of .019. The authors concluded that there is a significant reduction in risk of an event when trastuzumab is given sequentially after AC→T and that there is a trend towards benefit from concurrent trastuzumab with taxane compared with the sequential administration of these 2 drugs.

Results: At a median follow-up of 5.5 years, the 5-year DFS for AC→T versus AC→T→H is 72% versus 80% with a HR of 0.70. The 5-year DFS for AC→T→H versus AC→T/H→H was 80% versus 84% with a HR of 0.77 and a P-value of .019. The authors concluded that there is a significant reduction in risk of an event when trastuzumab is given sequentially after AC→T and that there is a trend towards benefit from concurrent trastuzumab with taxane compared with the sequential administration of these 2 drugs.

Results: The DFS and OS for the 3 arms are as follows.

Cardiac safety data were updated as well. There were no cardiac-related deaths on trial. Congestive heart failure was reported in 7 patients for AC→T, 21 for AC→TH, and 4 for TCH. A relative left ventricular ejection fraction (LVEF) decline of >10% was reported in 11%, 19% and 9%, respectively for these same groups. The authors concluded that trastuzumab provides a similar and significant advantage for both DFS and OS when used either with AC→T or TCarbo when compared to AC→T alone.

References
Perez EA, Suman VJ, Davidson NE, et al. Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial. Cancer Res. 2009;69(24 Suppl 3). Abstract 80 and oral presentation at: San Antonio Breast Cancer Symposium; December 9 – 13, 2009. San Antonio, TX.

Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study. Cancer Res. 2009;69(24 Suppl 3). Abstract 62 and oral presentation at: San Antonio Breast Cancer Symposium; December 9 – 13, 2009. San Antonio, TX.

Trastuzumab in the Metastatic Setting

Both trastuzumab and lapatinib are FDA approved for use in HER2–positive metastatic breast cancer. The combined use of these 2 agents was first reported at the 2008 American Society of Clinical Oncology (ASCO) annual meeting. Blackwell et al updated the data from this trial of 296 women with HER2-positive metastatic breast cancer. The women had to have progressed on anthracyclines, taxanes, and their most recent trastuzumab regimen. The women were randomized to receive lapatinib 1500 mg/day or lapatinib 1000 mg/day plus trastuzumab 2 mg/kg/week after a loading dose. For those patients randomized to lapatinib alone, they were allowed to crossover to the combined arm if they developed progressive disease after >4 weeks of therapy (n = 77). The primary endpoint was progression-free survival (PFS). For the women in this trial, the median number of prior chemotherapy regimens was 4 for the lapatinib arm, and 5 for the combined arm. The median number of prior trastuzumab regimens was 3 for each arm.

Results:
Factors that affected OS were as follows: treatment assignment, ECOG performance status, the site of disease (visceral versus nonvisceral), the number of metastatic sites, and the time from diagnosis to randomization. The majority of adverse events were grade 1 or 2. There were 3 grade 3/4 cardiac events in the combined arm and just 1 in the lapatinib alone arm. The authors concluded that combination therapy with lapatinib and trastuzumab should be considered for women in the metastatic setting.

Reference
Blackwell KL, Burstein HJ, Sledge GW, et al. Update survival analysis of a randomized study of lapatinib alone or in combination with trastuzumab in women with HER2-positive metastatic breast cancer progressing on trastuzumab therapy. Cancer Res. 2009;69(24 Suppl 3). Abstract 61and oral presentation at: San Antonio Breast Cancer Symposium; December 9 – 13, 2009. San Antonio, TX.

Anti-Angiogenic Therapy

The FDA has approved the use of bevacizumab in the front-line setting when combined with a taxane for women with metastatic breast cancer. However, for women who do not receive bevacizumab in the front-line setting, the benefit of bevacizumab is unknown.

The RIBBON-2 trial randomized 684 women with metastatic breast cancer who had undergone 1 prior chemotherapy regimen for their metastatic cancer. They were randomized in a 2:1 fashion to receive chemotherapy with or without bevacizumab. Chemotherapy regimens were defined and included the use of docetaxel, paclitaxel, albumin-bound paclitaxel, gemcitabine, vinorelbine, or capecitabine. The primary statistical endpoint was PFS. The chemotherapy regimen was determined by the investigator prior to the randomization.

Results:
At a median follow-up of 15 months, ORR for chemotherapy/placebo was 30% and was 39.5% with bevacizumab (P = .0193). The median PFS was 5.1 months versus 7.2 months, respectively without or with bevacizumab (P = .0072), and the median OS was 16.4 months versus 18 months (not statistically significant). Chemotherapy choices were as follows: taxanes (44%), gemcitabine (23%), capecitabine (21%), vinorelbine (11%). Adverse events were more common in the bevacizumab-treated patients, and were consistent with the known toxicities from bevacizumab, including hypertension and proteinuria.

Reference
Brufsky A, Bondarenko IN, Smirnov V, et al. RIBBON-2: A randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of HER2-negative metastatic breast cancer. Cancer Res. 2009;69(24 Suppl 3). Abstract 42 and oral presentation at: San Antonio Breast Cancer Symposium; December 9 – 13, 2009. San Antonio, TX.

To enhance the abstracts presented here from the 2009 San Antonio Breast Cancer Symposium, there are 9 “Best of the Day^SM” interviews from leading national and international breast cancer oncologists that are available in the Imedex E-Learning Center.

I hope that you have enjoyed this edition of OncoFacts and will look forward to next month’s edition.

OncoFacts™ Editor:

Christy Russell, MD

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