Results from the LUX-Lung 3 clinical trial show that afatinib appears to be well tolerated and more effective than chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. Afatinib produced higher response rates and longer periods without cancer progression than cisplatin (Platinol) plus pemetrexed (Alimta), suggesting that it could be considered as a first-line therapy in advanced EGFR-mutant NSCLC. Afatinib, which is under priority review for approval by the FDA, may be effective in patients resistant to other EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa). However, no trials so far have directly compared afatinib with Tarceva or Iressa.
The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation–positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).
In this phase III study, it was found that afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.
New guidelines recommend lung cancer patients be genetically tested to determine whether they are amenable to a class of drugs called tyrosine kinase inhibitors. Patients with EGFR or ALK mutations could benefit more from such targeted therapies, and suffer fewer side effects, than with chemotherapy. Continue reading…
Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.
Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf
The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.
A retrospective study in Japan examined 55 patients aged 75 years or over with inoperable non-small cell lung cancer (NSCLC) who had a mutation in the EGFR gene and received gefitinib (Iressa) as first-line therapy. The treatment was generally well tolerated and patients experienced longer periods without cancer progression (median: 13.8 months) and longer overall survival (median: 29.1 months) than commonly reported for similar patients. While studies using control groups will need to confirm that Iressa is indeed more effective than standard chemotherapy or a placebo, these findings suggest that Iressa may be a preferable first-line treatment in elderly patients with advanced EGFR-mutant NSCLC.
A study of individuals with and without lung cancer in North India found that those carrying a particular version (or “polymorphism”) of a gene for the protein p53 were more likely to have lung cancer, independent of their age or smoking rate. P53 belongs to a class of proteins called “tumor suppressor proteins,” and is involved in DNA repair, regulating cell growth, and inducing cell death in damaged or abnormal cells. The findings suggest that this version of the p53 gene, called Arg72Pro, may contribute to higher susceptibility for lung cancer, at least in the North Indian population.
Research paper: http://online.liebertpub.com/doi/full/10.1089/dna.2012.1792
A recent study examined first-line treatment with the chemotherapy agent carboplatin (Paraplatin), combined with either albumin-bound paclitaxel (Abraxane) or standard solvent-based paclitaxel (Taxol), in both elderly and younger patients with advanced non-small cell lung cancer (NSCLC). Patients treated with Abraxane/Paraplatin exhibited higher treatment response rates and fewer toxic side effects in both age groups; elderly patients (age 70+ years) experienced longer periods without cancer progression and longer overall survival with Abraxane/Paraplatin compared to Taxol/Paraplatin treatment. Abraxane plus Paraplatin may constitute a safe, effective first-line treatment for elderly patients with advanced NSCLC, a group that has been traditionally undertreated.
Research paper: http://annonc.oxfordjournals.org/content/24/2/314.long
Variations in genes for a family of proteins called matrix metalloproteases (MMPs) have been suggested to play a role in lung cancer risk. A meta-analysis of several studies on MMP genes found that a particular version (or “polymorphism”) of the MMP1 gene, called MMP1-1607 1G/2G, is associated with higher susceptibility for lung cancer in Asian patients. In contrast, the MMP2-1306 C/T version of the MMP2 gene decreases lung cancer risk in Asian patients and the MMP9-1562 C/T version of the MMP9 gene decreases lung cancer risk in white patients.