EGFR Inhibition Enhances the Cellular Uptake and Antitumor-Activity of the HER3 Antibody-Drug Conjugate HER3-DXd.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for -mutant non-small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of the ERBB family that functions by dimerizing with other ERBB family members (EGFR and HER2) and is frequently overexpressed in -mutant NSCLC.

Oncogenic switch and single-agent MET inhibitor sensitivity in a subset of -mutant lung cancer.

The clinical efficacy of epidermal growth factor receptor (EGFR)–targeted therapy in -mutant non–small cell lung cancer is limited by the development of drug resistance. One mechanism of EGFR inhibitor resistance occurs through amplification of the human growth factor receptor () proto-oncogene, which bypasses EGFR to reactivate downstream signaling. Tumors exhibiting concurrent mutation and amplification are historically thought to be codependent on the activation of both oncogenes.

Variation of Anatomical and Physiological Parameters that Affect Estimates of ACL Loading During Drop Landing.

Background: Anterior cruciate ligament (ACL) loading during drop landing has been recently studied with a sagittal plane knee model developed by Kernozek and Ragan using mean anatomical and physiological parameters obtained from cadaveric and clinical data. It is unknown how estimates in ACL load may be altered due to variations in anatomical and physiological parameters used from other research.

Methods: USING THE SAME MODEL, THESE PARAMETERS WERE SYSTEMATICALLY VARIED, INCLUDING: tibial slope, moment arms of the patellar tendon, hamstring, and gastrocnemius at the knee and ankle, patellar tendon and hamstring line of force, ACL stiffness, and nonlinear muscle activation parameters.

Results of a multicenter open-label randomized trial evaluating infusion duration of zoledronic acid in multiple myeloma patients (the ZMAX trial).

Zoledronic acid, an intravenous (IV) bisphosphonate, is a standard treatment for multiple myeloma (MM) but may exacerbate preexisting renal dysfunction. The incidence of zoledronic acid-induced renal dysfunction may correlate with infusion duration. In this randomized, multicenter, open-label study, 176 patients with MM, at least one bone lesion, and stable renal function with a serum creatinine (SCr) level < 3 mg/dL received zoledronic acid 4 mg (in 250 mL) as a 15- or 30-minute IV infusion every 3-4 weeks.

Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer.

Purpose: Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is approved as monotherapy for the treatment of metastatic colorectal cancer. We evaluated the association of tumor EGFR expression levels with outcomes in patients with chemorefractory metastatic colorectal cancer.

Experimental Design: Two phase II, multicenter, single-arm, open-label studies enrolled chemorefractory patients with tumors expressing low/negative (1-9%/<1%; Low/Negative EGFR study) or high (> or =10%; High EGFR study) levels of EGFR.

Results of a phase II open-label study of capecitabine in combination with irinotecan as first-line treatment for metastatic colorectal cancer.

Background: Between July 2001 and September 2002, 49 eligible patients were enrolled in an open-label phase II study to assess the efficacy and safety of first-line treatment with capecitabine/irinotecan in metastatic colorectal cancer.

Patients And Methods: Patients received capecitabine (1000 mg/m2 twice daily) on days 1-14 and irinotecan (240 mg/m2) on day 1 of a 21-day cycle. Patients enrolled had a median age of 64.