80% clinical response to tax+avastin+herceptin combo as 1st line mbc treatment --ASCO

[Lani]

Breast

Let's hope this keeps FDA from reversing approval of avastin for breast cancer!!!

We have to have drugs available so we can find out WHICH subgroup of breast cancer patients benefits from them!!! The cost to society will decrease as they eventually end up only using the drugs on those which will benefit from them

This study was supported by Roche/Genentech:

ASCO Breast: Tx Combo Helpful in Metastatic Breast Cancer



Almost 80% of patients with HER2-positive metastatic breast cancer had responses or stable disease in a small preliminary study of a chemotherapy-targeted therapy combination as first-line treatment.


Note that the study is ongoing, so these data must be considered preliminary

.
NATIONAL HARBOR, Md. -- Almost 80% of patients with HER2-positive metastatic breast cancer had responses or stable disease in a small preliminary study of a chemotherapy-targeted therapy combination as first-line treatment.
Eight of 18 patients had objective responses with the combination of trastuzumab (Herceptin), bevacizumab (Avastin), and docetaxel (Taxotere), and six others had prolonged stable disease. Median time to progression exceeded one year.

The regimen was generally well tolerated, including no increased risk of cardiotoxicity, according to a presentation here at the American Society of Clinical Oncology's Breast Cancer Symposium.

"The study is ongoing, so these data must be considered preliminary, but the combination has shown promising activity thus far," Bhuvaneswari Ramaswamy, MD, of Ohio State University in Columbus, told MedPage Today. "If the results continue to be favorable, eventually we would like to see this combination evaluated in a randomized trial."

HER2-positive breast cancers often have increased expression of vascular endothelial growth factor (VEGF). The combination of trastuzumab and the VEGF inhibitor bevacizumab has demonstrated activity in preclinical and clinical studies, including a 54% response rate in a small phase II study of first-line therapy for metastatic breast cancer, said Ramaswamy. However, cardiotoxicity complicated treatment in almost 40% of the cases.

Docetaxel has demonstrated single-agent activity in breast cancer, and has proven to be safe and effective in combination with either trastuzumab or bevacizumab.

Thus, the clinical history of the three drugs in breast cancer provided a strong rationale for using them in combination, Ramaswamy added.

To evaluate the combination, investigators enrolled patients with previously untreated HER2-positive metastatic breast cancer. Eligibility criteria included HER2 overexpression by immunohistochemistry (3+) or fluorescence in situ hybridization, normal left ventricular ejection fraction (LVEF), and no brain metastases.

All patients received six cycles of the three-drug combination, at which point docetaxel could be discontinued at physician discretion. Patients continued to receive the targeted therapies until disease progression or development of unacceptable toxicity. LVEF was assessed after every three cycles of therapy.

Ramaswamy reported data on the first 18 patients enrolled in the ongoing trial, including 16 patients evaluable for response. Grade 3-4 hematologic toxicity consisted of one case of neutropenia and two each of febrile neutropenia (one fatal) and infection.

Grade 3-4 nonhematologic toxicity consisted of one case each of nausea, vomiting, thrombosis, nephrotic syndrome, vision disturbance, fatigue, upper respiratory tract infection, and anorexia, and two cases of excessive tearing of the eyes.

One patient had an asymptomatic decline in LVEF and one had wound dehiscence.

Ramaswamy reported that eight patients had partial responses and six others had stable disease, resulting in a clinical benefit rate of 77.7% (14 of 18). Of 16 patients included in a survival analysis, median progression-free survival was 55.9 weeks. Six patients progressed or died.

Three patients had stable disease for more than six months, including one patient who has remained stable for more than two years while continuing targeted therapy.

Ramaswamy said accrual for the study continues at her institution and at the University of Pittsburgh. Data from correlational studies of circulating tumor cells and circulating endothelial cells will be reported at a later date, she said.

The study was supported by Genentech/Roche.

Ramaswamy and her coinvestigators declared they had no relevant disclosures.


Primary source: ASCO Breast Cancer Symposium
Source reference:
Ramaswamy B et al. "Phase II study of trastuzumab, docetaxel, and bevacizumab as first-line therapy in HER2-

[Rich66]

So they continued the Herceptin/Avastin after the cycles of Taxotere? I wonder if survival would be improved if Herceptin or Herceptin/Avastin was continued past progression.


Not sure I'm tracking this:

The regimen was generally well tolerated, including no increased risk of cardiotoxicity

However, cardiotoxicity complicated treatment in almost 40% of the cases.

So...same as other treatments i.e. 40%?

I wonder if there is any data on Taxotere/Herceptin without Avastin.

"Data from correlational studies of circulating tumor cells and circulating endothelial cells will be reported at a later date"

That would be interesting.

I'd also be curious about the combo with Abraxane instead of Taxotere.

[chrisy]

Rich, the 40% figure for cardiotoxicity was from a different trial.

I'm just guessing, but after progression on Herceptin/Avastin, many would continue on herceptin with another chemo, or move on to tykerb/xeloda. But drop the avastin.

I don't have it, but I'm sure there is an abundance of data out there on Taxotere/Herceptin alone; it's a standard first line therapy for MBC.

Not much information in the abstract tho - just enough to whet our appetites, and maybe this is part of the amended info the FDA got that caused them to defer their final decision for 3 months.