Predictive and prognostic factors in second- and third-line erlotinib treatment in NSCLC patients with known status of the EGFR gene.

Erlotinib is a reversible tyrosine kinase inhibitor of epidermal growth factor receptor (TKI EGFR). In Poland, as of July 2012, it is used in the treatment only of patients with non-small cell lung cancer (NSCLC) and with EGFR mutation gene after standard chemotherapy failure. The effectiveness of erlotinib in second- or third-line treatment of NSCLC patients without EGFR activating mutation gene remains debatable. Clinical trial results indicated that TKI EGFR showed an efficacy of 70­80% in patients with EGFR mutations, while the clinical response to treatment among unselected Caucasian patients is only 10%. The present study was conducted in a group of 71 patients with inoperable, locally advanced or metastatic NSCLC treated with erlotinib as the second- or third-line therapy. Molecular tests (examination of EGFR mutation and gene amplification) were carried out retrospectively. Objective response rate, overall survival (OS) and progression-free survival (PFS) were calculated. Effects of clinical and molecular factors including the presence of EGFR mutations, EGFR gene amplification, patient performance status, rash, smoking status, time from diagnosis to start of therapy, weight loss and the serum LDH levels were analyzed. An objective response in the form of partial response occurred in only 5 patients (7%), who carried EGFR gene mutation. Median time to PFS for the entire group of patients was 1.5 months and median OS was 10 months. The strongest factors increasing the risk of progression in patients treated with erlotinib were the absence of activating mutations in the EGFR gene (6­fold increased risk) and no treatment­related rash (4.5­fold increased risk). The most important factors affecting the risk of early mortality were poor performance status (HR 37.344; P>0.0001), no treatment-related rash (HR 14.9348; P=0.0002) and a short response time on the first-line chemotherapy (HR 9.519; P=0.0445).

Molecularly targeted therapies in head and neck cancers.

Head and neck cancers (HNC) are 6th most common malignancies according to the incidence rate. Over 85% of tumors of this region are epithelial tumors, especially squamous cell carcinomas (head and neck squamous cell carcinomas - HNSCC). Surgery, chemotherapy and radiotherapy are still the standard for the treatment of HNC. Despite the great development of the various methods of treatment, survival of patients have not improved significantly over the last 30 years, with the overall, 5-year survival not exceeding 50%. Progress in understanding the biology of cancer leads to personalization of therapy and introduction of drugs with molecular mechanism of action to everyday practice. At present, the effectiveness of monoclonal antibodies against EGFR in the treatment of HNSCC has already been proven. Cetuximab in combination with radiotherapy was found to be effective in patients with advanced and locally advanced HNSCC. There are also some promising results of phase III trials with zalutumumab and panitumumab. Initial efficacy of sorafenib (an inhibitor of the intracellular domain of VEGFR, PDGFR and c-Kit) and afatinib (an irreversible inhibitor of pan-HER tyrosine kinase) have been demonstrated. Great hopes for the future are linked with the potential use of STAT3, EGFRvIII, abnormal proteins K-ras, H-ras and PTEN as well as proteasome as a target for therapy.