Lung cancers with KRAS-related gene mutations might benefit from a triple therapy regimen of 2 experimental drugs plus radiation therapy, according to research done in mice. The results were published in Clinical Cancer Research (doi:10.1158/1078-0432.CCR-15-0589).
A clinical trial currently underway is evaluating the combination of trametinib and palbociclib, 2 cancer drugs from separate pharmaceutical companies for the treatment of melanoma and solid tumors, respectively, reported Bo Lu, MD, PhD, professor of radiation oncology at Thomas Jefferson University in Philadelphia, Pennsylvania, referring to clinical trial number NCT02065063.
“Although further research in human subjects is needed to confirm the finding, our study suggests that we may be able to identify non-small cell lung cancer patients who are likely to benefit most from this combination of therapies,” said Lu.
Approximately 85% of all lung cancers are the NSCLC type. Although advances have made in treating this disease, only 2% of survivors live 5 years beyond treatment. Drugs that target the ALK- and EGFR-mutated subtypes are effective to some degree; however, 1 genetic subset of NSCLC (KRAS-mutant) has been resistant to conventional and targeted therapies.
In this study, Lu and colleagues investigated the KRAS-mutant subset in NSCLC cells and found a variation within this subset; some tumors were more resistant to a drug that targeted the KRAS gene pathway than others. An additional mutation in the p16 protein appeared to account for this difference. A scan of a database of lung-cancer patient genotypes showed that overall survival was lower in patients with the p16 mutation than in those without the mutation.
To help make these resistant KRAS-mutant cancers more susceptible to therapy, the researchers combined the KRAS-targeting drug with another drug that would undo the effects of the p16 mutation. Lu’s group showed that the combination of the 2 drugs make the resistant cancer cells susceptible to radiation treatment.
Currently, neither of the 2 drugs that target KRAS and proteins in the p16 pathway are approved for the treatment of lung cancer. Lu hopes this research will help identify those patients who could potentially benefit from the triple-therapy treatment.