Vinflunine + Herceptin Interesting Prelim Data

[Cynthia]

The following early trial results show promise for a combination of vinflunine + Herceptin as a first line therapy for Her 2+ metastatic breast cancer. See the links below for trial information. (The second link references a similar trial for second line therapy but it doesn't look like it has opened yet, though I encourage anyone interested to look into it.)

Peacock NW, Spigel DR, Mainwaring MG, et al. Preliminary results of a

multicenter phase II trial of vinflunine (with trastuzumab in HER2+

pts) as first-line treatment in metastatic breast cancer. Abstract 1043.

* Phase II, multicenter, open-label study

* Combination of vinflunine and trastuzumab active as first-line

therapy in HER2-positive metastatic breast cancer (MBC) (Only 17

evaluable patients, but 47% had a partial response, and 35% had

stable disease, for a clinical benefit of 82%)

*Very well tolerated

No febrile neutropenia

No grade 3/4 neuropathy

* Vinflunine a promising novel agent and further investigation

indicated (small study)

* Ongoing, randomized, phase III trial of vinflunine plus trastuzumab

vs paclitaxel plus trastuzumab as first-line therapy for MBC

Abstract:

Background: Vinflunine (VFL) is a new and innovative microtubule

inhibitor of the vinca alkaloid class that achieves high

intracellular concentrations. By inhibition of tubulin

polymerization, cell proliferation is arrested leading to apoptotic

death. Demonstrating anti- angiogenic and vascular disrupting

activities, VFL has demonstrated significant efficacy as 2nd line

chemotherapy in MBC (M. Campone, BJC 2006). This trial was designed

to evaluate the response rate and safety of VFL as 1st line therapy

in MBC as well as its activity in combination with trastuzumab in

HER2+ MBC pts.

Methods: Eligibility: 0 prior regimens for MBC, > 6 mo from adjuvant

therapy, RECIST measurable disease, ECOG PS 0-2, adequate organ

function, < G2 neuropathy. Treatment: 320 mg/m2 IV over 20 minutes q3

weeks; 280 mg/m2 with trastuzumab 6 mg/kg q3 weeks in HER2+ pts.

Response evaluations q9 weeks; treatment continued until progression

or toxicity. A total of 96 pts will be enrolled, 48 pts per each of 2

cohorts, HER2- and HER2+.

Results: 18 pts are enrolled, 13 pts evaluable for toxicity and 12

pts for response. 3 pts received VFL monotherapy and 10 pts were

treated with VFL + trastuzumab. Median age: 59 years (43-78). ECOG PS

0: 9 pts, 1: 3 pts, 2: 1 pt. Prior adjuvant chemo: 7 pts (54%), with

5 prior anthracyclines and 6 prior taxanes. 2 pts received adjuvant

hormonal therapy only. 4 pts presented with de novo stage IV HER2+

MBC. Metastatic disease sites: liver: 6 pts, lung: 7 pts, bone: 5

pts, lymph nodes: 6 pts. 46% had 3 or more sites of organ

involvement. Median of 3 cycles (range:1 - 11) was delivered. 7 pts

(58%, all HER2+) had a PR and 4 pts (33%) achieved SD. Only 1 pt

progressed. Heme toxicity: G3/4 neutropenia: 2 pts (16%); no febrile

neutropenia was noted. G3 non-heme toxicity consisted of N/V: 2 pts

and myalgia, 2 pts. There were no G4 events. 4 pts were hospitalized

(vomiting: 2, cerebro-vascular accident: 1, back pain: 1 pt). 92% of

pts remain free of progression at 6 months. Median TTP has not been reached.

Conclusions: Vinflunine is a promising new drug with a high level of

activity as first line MBC therapy, especially in combination with

trastuzumab. VFL is well tolerated in this patient population with a

manageable toxicity profile. Accrual to this trial continues.

** Clinical trials: http://clinicaltrials.gov/ct/show/NCT00284180?order=1

http://clinicaltrials.gov/ct/show/NCT00450515?order=2