Hope S. Rugo, MD, is the Director of the Women's Cancers Program, the Division Chief of Breast Medical Oncology, and a Professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center. She is also a Professor Emeritus at UCSF

Hope S. Rugo, MD, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discusses a phase III randomized trial that compared the two new agents, nab-paclitaxel (Abraxane) and ixabepilone (Ixempra), to the standard weekly agent paclitaxel (Taxol) for patients with locally advanced or metastatic breast cancer.

The trial provided all three agents weekly for a three-week cycle followed by a one-week break. Rugo notes that this schedule for ixabepilone will no longer be used in practice, because of the observed increase in toxicities. However, the three-week schedule for nab-paclitaxel was effective.

This trial established that paclitaxel is an effective drug and performed as good or better than the newer and more expensive competitors examined on the trial, at the weekly dosing examined. Additionally, Rugo notes that less toxicity was observed with paclitaxel than the other two drugs.

Rugo notes that paclitaxel should remain the standard first-line therapy with nab-paclitaxel second-line for patients who have progressed. Nab-paclitaxel works well in the second-line setting because it does not require premedication with a steroid. Rugo notes that the standard dose for nab-paclitaxel should remain 100 mg/m

; the trial examined increasing the dose to 150 mg/m

 but this resulted in increased toxicity without any additional benefits.

Videos

Dr. Hope Rugo, from the UCSK Comprehensive Cancer Center, on the First-line Superiority of Paclitaxel for Advanced Breast Cancer.

Dr. Rugo on Paclitaxel Superiority in Advanced Breast Cancer

Hope S. Rugo, MD, clinical professor, Department of Medicine (Hematology/Oncology), and director, Breast Oncology Clinical Trials Program, University of California, San Francisco, discusses the efficacy of bevacizumab (Avastin) at treating breast cancer.

Gauge the efficacy of bevacizumab is difficult because there are still many unknowns. The best dosing schedule and the patient populations that are most effected is still unclear. Although the ability to reverse resistance and improved progression-free survival has been demonstrated the cessation of the drug can increase malignant angiogenesis. The pros and cons still remain unclear.

Rugo postulates that a more thorough understanding of the subgroups could help predict a greater benefit to the drug. In addition to the populations a closer look needs to be concentrated on whether the drug is best given in combination with chemotherapy alone or with other targeted therapies. It is clear from studies in glioblastoma that when you stop the drug you get enhanced angiogenesis. This is another concern that needs to be addressed.

The future of research and funding for bevacizumab remains unclear; this stresses the importance of being careful and cautious when seeking accelerated approvals.

Dr. Hope S. Rugo from the University of California, San Francisco on the Efficacy of Bevacizumab in Breast Cancer

Dr. Rugo on the Efficacy of Bevacizumab in Breast Cancer

Hope S. Rugo, MD, clinical professor, Department of Medicine (Hematology/Oncology); and Director, Breast Oncology Clinical Trials Program, University of California, San Francisco, discusses the idea of using proliferation as a marker to predict response to angiogenesis inhibitors.

Rugo uses the investigation of PARP inhibitors such as iniparib in triple-negative breast cancer (TNBC) as an example of how hard it is to find a single marker that predict response in breast cancer.

The trials investigating PARP discovered that TNBC is a very heterogeneous disease that contains multiple intrinsic subtypes. Using only immunohistochemistry criteria to predict response to anti-angiogenesis will not work because of tumor heterogeneity.

Dr. Hope S. Rugo from University of California, San Francisco on Proliferation as an Anti-Angiogenesis Marker

Dr. Rugo on Proliferation as an Anti-Angiogenesis Marker

Hope S. Rugo, MD, clinical professor, Department of Medicine (Hematology/Oncology); and Director, Breast Oncology Clinical Trials Program, University of California, San Francisco, discusses the AVADO trial that investigated VEGF levels as a predictor of response to antiangiogenesis agents, particularly bevacizumab (Avastin).

A retrospective analysis of the data present by David W. Miles, MD, suggested that if VEGF-A levels were divided into quartiles the highest quartet level predicted higher response rates to bevacizumab.

Dr. Hope Rugo from UCSF Cancer Center on VEGF-A as an Avastin Response Predictor

Dr. Rugo on VEGF-A as an Avastin Response Predictor

Hope S. Rugo, MD, clinical professor, Department of Medicine (Hematology/Oncology); and Director, Breast Oncology Clinical Trials Program, University of California, San Francisco, explains that the future of angiogenesis inhibitors is an extremely complicated area.

Rugo expresses that the first step was to establish how important angiogenesis is in malignant progression, invasion, metastasis, and survival of metastatic disease. It is clear that angiogensis does play a role in tumor progression but that role has not yet been fully defined.

The process of angiogenesis has many functions both in tumors and normal cell function and this makes it extremely difficult to work with. In the future she believes combination therapies will need to be used in more effective and smarter ways in order to increase the efficacy of anti-angiogenesis treatments.

Dr. Hope S. Rugo from UCSF Cancer Center on the Future of Angiogenesis in Breast Cancer

Dr. Rugo on the Future of Angiogenesis in Breast Cancer

Hope S. Rugo, MD, clinical professor, Department of Medicine (Hematology/Oncology); and Director, Breast Oncology Clinical Trials Program, University of California, San Francisco, discusses the need for further development and investigation into response and resistance predictors of anti-angiogenesis therapy in breast cancer.

Some agents that block angiogenesis, such as bevacizumab (Avastin), are known to have an effect but an adequate method of predicting resistance and which breast cancer tumors will respond still needs to be investigated.

Rugo explains that active trials are underway examining predictive factors such as the use of host genomics to predict toxicity and response. At this point due to the complicated nature of host genetics it may be better used as a predictor of toxicity rather than for efficacy. Many of these pharmacogenetics or polymorphisms of genes that were discovered in the ECOG 2100 trial examining metastatic breast cancer are now being investigated in the adjuvant trial ECOG 5103.

Dr. Hope S. Rugo from University of California, San Francisco on Anti-Angiogenesis Therapy Response Predictors

Hope S. Rugo, MD

Articles

Dr. Rugo on Paclitaxel Superiority in Advanced Breast Cancer

Dr. Rugo on the Efficacy of Bevacizumab in Breast Cancer

Dr. Rugo on Proliferation as an Anti-Angiogenesis Marker

Dr. Rugo on VEGF-A as an Avastin Response Predictor

Dr. Rugo on the Future of Angiogenesis in Breast Cancer

Dr. Rugo on Anti-Angiogenesis Therapy Response Predictors