ASCO 2014 Lung Cancer Roundup

Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…

On the Failure of Lung Cancer Drug Onartuzumab in a Phase III Clinical Trial

Most new cancer drugs fail clinical testing. Because they don’t make it to the pharmacy, we usually hear very little about them. But widespread media coverage made it hard to ignore the recent termination of a trial testing the drug onartuzumab. Details of the story raise concerns about the patient enrollment processes of some clinical trials. Continue reading…

Committee: NSCLC Study Should be Halted Due to Lack of Efficacy

“An independent data monitoring committee recommended that a phase 3 study designed to evaluate the combination of onartuzumab and erlotinib in a subset of patients with non–small cell lung cancer be stopped due to lack of clinically meaningful efficacy, according to a press release issued by the drugs’ manufacturer.

“The randomized, multicenter, double-blind, placebo-controlled MetLung study compared the humanized monoclonal antibody onartuzumab (MetMab, Genentech) plus the protein kinase inhibitor erlotinib(Tarceva, Genentech) vs. erlotinib alone in patients with previously treated advanced NSCLC whose tumors were MET-positive.”

Outcome Improved in MET-Positive and Worsened in MET-Negative NSCLC With Addition of Onartuzumab to Erlotinib in Phase II Trial

In patients with non–small cell lung cancer (NSCLC), increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to EGFR-targeted treatment. In a phase II study reported in the Journal of Clinical Oncology, David R. Spigel, MD, of Sarah Cannon Research Institute, and colleagues examined whether dual inhibition of MET/EGFR with the anti-MET monoclonal antibody onartuzumab and erlotinib (Tarceva) could provide clinical benefit in patients with advanced NSCLC. They found that the combination improved progression-free survival and overall survival among MET-positive patients but not among MET-negative patients.

Effect of New Lung Cancer Drug Depends on MET Protein Expression Levels

The cell protein MET is overexpressed in more than half of non-small cell lung cancer (NSCLC) tumors. MET overexpression is associated with worse prognoses and plays a role in drug resistance to EGFR inhibitors like erlotinib (Tarceva). A recent clinical trial examined the effects of onartuzumab, which inhibits MET function, on recurrent NSCLC. Patients received either onartuzumab and Tarceva or Tarceva only. In patients who overexpressed MET, adding onartuzumab increased the time until cancer progression and prolonged overall survival. In contrast, in patients without MET overexpression, adding onartuzumab worsened outcomes. This finding highlights the importance of diagnostic testing in choosing the best cancer treatment. A clinical trial investigating the onartuzumab-Tarceva combination in MET-overexpressing patients only is currently enrolling participants.

Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer

Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) –targeted drugs in patients with non–small-cell lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC.

Onartuzumab plus erlotinib was associated with improved progression-free survival and overall survival in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development.

Avastin-Containing Chemotherapy May Be Safe in Lung Cancer Patients with Brain Metastases

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:

Overexpression of IGF1R and EGFR Genes May Worsen Lung Cancer Prognosis

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.

Research paper:

Study Suggests Iressa Effective for Elderly Patients with EGFR-Mutant Lung Cancer

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.

Research paper: