Entry Detail
| General information | |
| Database: | DB00709 |
| Objective: | This was a pilot study to assess the biologic effects of lapatinib on various tumor growth/survival pathways in patients with advanced ErbB1 and/or ErbB2overexpressing solid malignancies. |
| Authors: | Spector NL, et al |
| Title: | Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. |
| Journal: | J Clin Oncol. |
| Year: | 2005 |
| PMID: | 15684311 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumours |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a pilot openlabel, randomized trial study |
| Key Patients Feature: | Patients providing informed consent were enrolled onthis openlabel, randomized trial if their tumors (1) overexpressedErbB2 and/or ErbB1 (2 to 3 immunohistochemistry [IHC]staining in 10% of tumor cells), or (2) demonstrated ErbB2gene amplification by fluorescent in situ hybridization. Additionaleligibility criteria included: age $18 years; measurable metastaticsolid malignancies not amenable to established standard therapies; Karnofsky performance status more than and equal to 70; no prior chemo, radio, hormonal or immunotherapy within the previous 4 weeks;left ventricular ejection fraction more than and equal to 40%; hemoglobin more than and equal to 9 g/ml; absolute neutrophil countmore than and equal to 1, 500/ L; plateletmore than and equal to 100, 000/ L; totalbilirubin 2.0 mg/dL, and transaminases < 3 upper limit ofnormal unless due to tumor |
| Biomarker: | overexpressing ErbB2 and/or expressing ErbB1 |
| Biomark Analysis: | Clinical response was associated with a pretreatment TUNEL score > 0 and increased pretreatment expression of ErbB2, pErbB2, Erk1/2, pErk1/2, insulinlike growth factor receptor1, p70 S6 kinase, and transforming growth factor alpha compared with nonresponders. |
| Control Group Info: | single arm |
| Treatment Info: | pts were randomly assigned to one of five dose cohorts of lapatinib (GW572016) administered orally once daily continuously. The biologic effects of lapatinib on tumor growth and survival pathways were assessed in tumor biopsies obtained before and after 21 days of therapy. Clinical response was determined at 8 weeks. |
| Primary End Point: | biologic effects of lapatinib on various tumor growth/survival pathways |
| Secondary End Point: | NA |
| Patients Number: | 33 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Partial responses occurred infour patients with breast cancer, and disease stabilization occurred in 11 others with variousmalignancies |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | Lapatinib exhibited preliminary evidence of biologic and clinical activity in ErbB1 andor ErbB2overexpressing tumors. Hotheyver, the limited sample size of this study and the variability of the biologic endpoints suggest that further work is needed to prioritize biomarkers for diseasedirected studies, and underscores the need for improved trial design strategies in early clinical studies of targeted agents. |