Trial of Vinflunine Versus Alkylating Agent in Metastatic Breast Cancer
Condition: Breast Cancer; Metastases
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      In metastatic breast cancer (MBC) patients who have already received anthracyclines, taxanes,
      antimetabolites and vinca-alkaloids and have developed drug resistance to these drugs,
      therapeutic options are very limited. Alkylating agents showed a modest activity in
      pretreated metastatic breast cancer. This phase III trial will compare the effectiveness and
      the safety profile of vinflunine to an alkylating agent of physician choice in MBC patients
      who have exhausted anthracyclines, taxanes, antimetabolites and vinca-alkaloids.
    

Detailed description: 
      Breast cancer is the most frequently diagnosed cancer in women worldwide and the second
      leading cause of cancer-related deaths in women.

      Patients with metastatic breast cancer (MBC) remains incurable, and current goals of therapy
      are to ameliorate symptoms, delay disease progression, improve or at least maintain quality
      of life (QoL), and prolong overall survival (OS).There are a number of agents with
      established single-agent activity, with the anthracyclines and taxanes considered generally
      the most active. In addition, several drugs with different mechanisms of action such as
      antimetabolites and vinca-alkaloids have also demonstrated substantial activity in the
      metastatic setting as single-agents or in combination.

      In patients who progress after having received anthracyclines, taxanes, antimetabolites and
      vinca- alkaloids, therapeutic options are scarce. In this heavily pretreated population for
      whom overall survival is not expected to exceed 6 to 7 months, there is a clear need for
      novel therapies.

      Vinflunine (VFL) is a microtubule inhibitor obtained by semi-synthesis, interacts with
      tubulin at the vinca-binding domain and inhibits tubulin assembly by perturbing microtubule
      dynamics and mitotic spindles without affecting assembled microtubules. VFL antitumour
      activity was fully demonstrated against a large and varied panel of murine and xenograft
      models.

      The main haematological toxicity reported was the neutropenia Grade 3-4 (40-50%). The
      incidence of its complications (febrile neutropenia and neutropenic infection) was less than
      8%. The main non-haematological toxicity Grade 3-4 (with an incidence more than 10%) reported
      were constipation and fatigue.

      This was a prospective multicentre, open-label, randomised (1:1), phase III study comparing
      OS in patients treated with vinflunine versus those treated with an alkylating agent of
      physician's choice as third line treatment or more for patients with locally recurrent and/or
      metastatic breast cancer previously treated with and no longer candidate to anthracyclines,
      antimetabolites, taxanes and vinca- alkaloids..

      The primary endpoint for the trial was OS. Patients were assessed for toxicity, tumour
      response and progression and status (alive-dead) at regular intervals during the study
      treatment and the follow-up period. Patients were treated until disease progression,
      unacceptable toxicity, patient or investigator's decision. After the study treatment
      discontinuation, patients were followed until death.

      The VFL dose of 280 mg/m² was the selected dose for this phase III study in patients with
      heavily pre- treated MBC. Indeed, VFL dose was reduced from 320 to 280 mg/m² in advanced
      transitional cell carcinoma of urothelial tract patients with performance status (PS) of 1 or
      with PS of 0 and having received prior pelvic irradiation. This dose was more regularly
      tolerable in patients with advanced disease stage who were heavily pre-treated.
    

Intervention name(s): vinflunine; Alkylating agent of physician choice registered in cancer
Intervention type(s): Drug; Drug
Intervention description(s): 280 mg/m2 on day 1 of each cycle every 3 weeks; cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Other intervention name(s): JAVLOR; L00070; Various
Intervention MeSH terms: Alkylating Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment