An ongoing clinical trial is evaluating the effects of cancer drug tivantinib in non-small cell lung cancer (NSCLC). The trial studies patients with advanced non-squamous NSCLC who do not have any mutations in the EGFR gene. Patients receive erlotinib (Tarceva) either by itself or in combination with tivantinib. Enrollment in the trial was stopped because rates of interstitial lung disease (ILD), which can cause lung scarring, may be higher in patients receiving tivantinib. (No such increased levels of ILD were seen in a different trial using tivantinib.) For the patients already enrolled, overall survival, time without cancer worsening, and percentage of patients experiencing tumor shrinkage all seem increased in tivantinib-treated patients. However, it is not yet clear whether these effects are indeed caused by tivantinib or are due to chance.
An early clinical trial of the drug MK-3475 in non-small cell lung cancer (NSCLC) has yielded promising results. MK-3475 targets PD-1, a protein on the surface of immune cells. Another protein, PD-L1, is present on many tumor cells and can bind to PD-1, which deactivates immune cells. MK-3475 blocks PD-1, allowing the immune cells to keep attacking cancer cells. Patients with advanced NSCLC who had failed at least two other treatments were given MK-3475. Tumors shrank in 24% of the patients overall. However, tumor shrinkage occurred in 67% of patients with high levels of PD-L1 on their tumors, compared to only 9% of others. PD-L1 levels may therefore help predict which patients will likely respond to MK-3475.
A new clinical trial will investigate the safety of vantictumab (OMP-18R5), a new lung cancer drug targeting cancer stem cells (CSCs). CSCs, the actively multiplying cells responsible for generating tumors, are thought to be central in cancer relapse by ‘repopulating’ tumors, even if the bulk of the tumors cells are destroyed during treatment. Vantictumab blocks the Wnt pathway, a key molecular signaling pathway used by CSCs. Patients with previously treated advanced non-small cell lung cancer (NSCLC) will receive vantictumab in combination with the chemotherapy agent docetaxel (Taxotere). In addition to the safety of the drug combination, the trial will also investigate how effective it is and whether any biomarkers predict how well patients respond.
A phase II clinical trial examined the use of the chemotherapy drug docetaxel (Taxotere) combined with everolimus (Afinitor), a member of a family of drugs called mTOR inhibitors, as second- or third-line treatment in advanced non-small-cell lung cancer (NSCLC). The treatment was well tolerated, but only modestly effective compared to standard therapy in similar patients. The patients in the study had not been selected for any specific biomarkers; better effectiveness may be achieved in patients with relevant biomarkers.