There remains an unmet need for treatment options for patients with squamous cell non-small cell lung cancer (NSCLC), heightening the need for novel therapies. At the 2014 European Society for Medical Oncology (ESMO) Congress held this month in Madrid, Spain, preliminary data from a randomized, international phase 2 trial demonstrated an improvement in outcomes with the combination of the PARP inhibitor veliparib and chemotherapy.
In the study, progression-free survival was improved by 35 percent and overall survival was extended by 30 percent with the combination of veliparib with chemotherapy in patients with newly diagnosed metastatic or advanced NSCLC. In patients specifically with squamous histology, progression-free survival was 6.1 months with veliparib compared with 4.1 months, and the overall survival was 10.3 months with veliparib compared with 8.4 months. Side effects include a decrease in a type of white blood cells, which could raise the risk of infection.
Based on these results, a phase 3 study has been initiated for patients with squamous cell NSCLC.
Suresh S. Ramalingam, director of medical oncology and the lung cancer program at the Winship Cancer Institute of Emory University, discussed the results of the trial and the potential of veliparib as a treatment for patients with squamous cell NSCLC in an interview with OncLive, a partner company of CURE.
How was it discovered that veliparib had utility in lung cancer?
Ramalingam: PARP is a protein that’s involved in DNA repair, and veliparib is a very potent inhibitor of PARP1 and PARP2. Basically, when you give a PARP inhibitor, the cell is not able to repair DNA damage effectively. What we’ve seen in the past is if the cells have deficiency in homologous recombination repairs, which is what happens in BRCA mutation settings, those cells become far more dependent on the basic repair pathway, which is exactly where the PARP comes into play. Even though the role of PARP is well known beyond that.
So essentially by blocking DNA in cells that are critically dependent on that pathway, you are able to induce lethal damage. In lung cancer, if you look at what the common modalities of treatment are, we use platinum compounds, which are the cornerstones of therapy, and then we use radiation and both of these work by inducing DNA damage. Cells that can repair the DNA damage end up not being sensitive to radiation or chemotherapy with platinum-based regimens.