Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions.

BACKGROUND: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected. RESULTS: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had <10 pg mutated genomes/µl with allelic fractions below 0.25%. Patients treated first line with TKIs based exclusively on EGFR positivity in blood had an ORR of 72% and a median PFS of 11 months. Of 105 patients screened after progression to EGFR-TKIs, sensitizing mutations were found in 56.2% and the p.T790M resistance mutation in 35.2%. CONCLUSIONS: Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

The expanding role of pertuzumab in the treatment of HER2-positive breast cancer.

Breast cancer tumors that demonstrate gene amplification or overexpression of human epidermal growth factor receptor 2 (HER2) are classified as HER2-positive. They account for approximately 15% of all breast cancers and represent an adverse prognostic factor. Over the past years, many new therapies have become available for the treatment of breast cancer. Particularly, the treatment of patients with HER2-positive breast cancer has developed with the arrival of anti-HER2 targeted therapies that have been proven to increase survival in both the metastatic and early-stage settings of the disease. Trastuzumab, a monoclonal antibody targeting HER2, significantly improves survival in HER2-positive breast cancer. Nevertheless, it is still a challenge to evolve anti-HER2 therapies, as the disease may progress. Pertuzumab inhibits HER2 by binding to a different HER2 epitope than trastuzumab and represents a complementary mechanism of action to trastuzumab. The efficacy and safety of pertuzumab in combination with trastuzumab with or without chemotherapy have been demonstrated in both advanced and early stages of HER2-positive breast cancer. Herein, we review the available data on the use of pertuzumab for the treatment of patients with HER2-positive breast cancer.

Haemolytic uraemic syndrome associated with gemcitabine

Haemolytic uraemic syndrome (HUS) is a rare thromboembolic complication observed in patients with cancer. It is characterised by the clinical triad of acute renal failure, microangiopathic haemolytic anaemia and thrombocytopaenia. It may be associated with a variety of aetiologies, including chemotherapeutic agents such as mitomycin, cisplatin, bleomycin, 5-fluorouracil and, most recently, gemcitabine. We report a 70-year-old patient treated with gemcitabine who developed haemolytic uraemic syndrome (AU)