Final Results Of A First Line Multicenter Phase Ii Metastatic Breast Cancer Trial Of Vinflunine Monotherapy And In Combination With Trastuzumab In Her2+Patients

Abstract #3148 Background: Vinflunine (VFL) is a novel microtubule inhibitor agent of the vinca alkaloid class that inhibits tubulin polymerization without stabilization, resulting in cell cycle arrest in mitosis and apoptosis. Weak tubulin binding at the vinca-binding site accounts for its reduced neurotoxicity. VFL has demonstrated activity in anthracycline and taxane pretreated patients (pts) and in combination with capecitabine. This trial evaluates the activity and safety of VFL monotherapy and in combination with trastuzumab (T) in HER2+ pts as 1 st line therapy metastatic breast cancer (MBC). Methods: Eligibility: 0 prior regimens for MBC, > 6 mo from adjuvant therapy, RECIST criteria measurable disease, ECOG PS 0-2, adequate organ function, peripheral neuropathy 2 IV q3 wks; FISH HER2+ pts: VFL 280 mg/m 2 plus T 6 mg/kg q3 wks. Response evaluations q9 wks; treatment continued until disease progression or toxicity. Results: Due to termination of VFL licensing between BMS and Pierre Fabre Medicament, the study closed prematurely with only 31 evaluable pts of a planned 48 pts in each treatment arm of VFL monotherapy or VFL in combination with T. 10 pts received VFL and 21 pts were treated with VFL + T. Median age: 59 yrs (35-78). ECOG PS 0-18 pts, 1-11 pts, 2-2 pts. 48% were ER+. Prior adjuvant anthracyclines and taxanes noted in 17 and 19 pts respectively. 4 pts presented with de novo stage IV disease, all HER2 positive. 45% had 3 or more metastatic disease sites with bone (17 pts), liver (16 pts) and lung (15 pts) predominating. Median of # cycles: 4 (range 1-19). There were 10 PRs (32%), all in VFL + T, and 9 pts (29%) with PD (VFL-4 pts, VFL + T-5pts). SD was reported in 10 pts (32%). 2 pts (7%) were unevaluable, divided equally between the two arms. G3/4 neutropenia occurred in 11 pts (35%); none with fever . G3 nonhematologic toxicity consisted of pain, attributed to treatment in 5 pts (16%) (sites: abdomen-2, chest, back, and infusion site each in 1 pt), and GI toxicity characterized by N/V 3 pts (10%) as well as abdominal pain, diarrhea, constipation, occurring each in 2 pts (6%). There were no G4 events. 10 pts were hospitalized (GI -4 pts, pain 2 pts, pulmonary 2 pts, and other 2 pts). Median PFS was 3.5 months for VFL and 6.6 months for VFL + T. Median overall survival was 9 months for VFL and has not been reached for VFL + T. Conclusions: The combination of vinflunine and trastuzumab is active in the first line treatment of MBC, producing a 48% response rate. Adverse events were as expected, manageable and consisted primarily of neutropenia, pain and GI toxicity. This encouraging activity compares favorably with other trastuzumab combination regimens and merits further evaluation. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3148.