title: Phase II study evaluating lapatinib in combination with nab-paclitaxel in HER2-overexpressing metastatic breast cancer patients who have received no more than one prior chemotherapeutic regimen.
abstract: Lapatinib, an oral, reversible inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) tyrosine kinase, has proven antitumor activity in HER2-positive metastatic breast cancer (MBC). Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. This was an open-label, single-arm, multicenter, Phase II study to evaluate the efficacy and safety of nab-paclitaxel plus lapatinib in women with HER2 over-expressing MBC who had received no more than one prior chemotherapeutic regimen. The primary efficacy endpoint was the overall response rate (ORR). This was defined as the percentage of patients having either a complete response (CR) or partial response (PR). Secondary efficacy endpoints included progression-free survival (PFS), overall survival, duration of response (DoR), time to response (TTR), and time to progression (TTP). Investigator-assessed ORR was 53 % (n = 32, 95 % confidence interval (CI): 40.7-66.0) with the majority of patient responses demonstrating a PR (47 %). Four (7 %) patient responses demonstrated a CR, and ten (17 %) a stable disease. The median Kaplan-Meier estimate of investigator-assessed PFS, DoR, TTR, and TTP was 39.7 weeks (95 % CI 34.1-63.9), 48.7 weeks (95 % CI 31.7-57.1), 7.8 weeks (95 % CI 7.4-8.1), and 41 weeks (95 % CI 39.1-64.6), respectively. Lapatinib 1,000 mg with nab-paclitaxel 100 mg/m(2) IV is feasible with manageable and predictable toxicity and an ORR of 53 % comparing favorably with other HER2-based combinations in this setting.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA. dyardley@tnonc.com
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Lowell
authors.initials: L
authors.lastname: Hart
authors.forename: Linda
authors.initials: L
authors.lastname: Bosserman
authors.forename: Mansoor N
authors.initials: MN
authors.lastname: Salleh
authors.forename: David M
authors.initials: DM
authors.lastname: Waterhouse
authors.forename: Maura K
authors.initials: MK
authors.lastname: Hagan
authors.forename: Paul
authors.initials: P
authors.lastname: Richards
authors.forename: Michelle L
authors.initials: ML
authors.lastname: DeSilvio
authors.forename: Janine M
authors.initials: JM
authors.lastname: Mahoney
authors.forename: Yasir
authors.initials: Y
authors.lastname: Nagarwala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C520255:130-nm albumin-bound paclitaxel; C508053:ERBB2 protein, human