Small cell lung cancer (SCLC) usually responds well to initial chemotherapy, but frequently relapses within a short time. Maintenance therapy with the drug sunitinib (Sutent) may delay relapse and improve outcomes for SCLC patients, results from a recent phase II clinical trial suggest. Patients with extensive-stage SCLC who had responded to initial chemotherapy were given either Sutent as maintenance therapy or a placebo. Sutent, a tyrosine kinase inhibitor (TKI) that blocks several proteins involved in SCLC, prolonged the time without cancer progression (3.2 months on average, compared to 2.3 months in the placebo-treated patients). Patients receiving Sutent also tended to have longer overall survival (8.9 months vs 6.9 months with placebo), although this finding was not clear enough to determine whether it was due to chance. The survival difference between patient groups may have been smaller because placebo-treated patients whose cancer relapsed were allowed to switch to Sutent, suggesting that Sutent may actually have more definite effects on patient survival.
A certain type of mutation in a protein, called RET, occurs in a significant subset of lung cancer patients, a recent study shows. Known as ‘rearrangements,’ these mutations fuse the RET gene with other nearby genes, resulting in a RET protein that contains parts of other proteins and is hyperactive. Patients with similar rearrangement mutations in another gene, ALK, can experience drastic improvements from treatment with ALK inhibitors such as crizotinib (Xalkori). This raises the hope that patients with RET rearrangement mutations may be similarly helped by drugs that block RET–either novel RET inhibitors or existing tyrosine kinase inhibitors (TKIs), such as vandetanib (Caprelsa), sunitinib (Sutent), sorafenib (Nexavar), or ponatinib (Iclusig). Identifying patients who may benefit from such treatments would be made easier by the new test for RET mutations developed by the study’s authors. When examining a group of patients with lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC), who did not have mutations in other cancer-relevant genes, the researchers found that 15% had RET rearrangement mutations.
An analysis of multiple clinical trials compared erlotinib (Tarceva) alone to combining Tarceva with other targeted therapies as second-line treatment for advanced non-small cell lung cancer (NSCLC). In the various trials, Tarceva was combined with bevacizumab (Avastin), bortezomib (Velcade), everolismus (Afinitor), sorafenib (Nexavar), sunitinib (Sutent), entinostat, tivantinib, and R1507. While combined therapy produced more side effects, it was more effective than Tarceva alone. Notably, the trials included many patients who had not been tested for mutations in the EGFR and KRAS genes. In patients who had EGFR mutations and/or lacked KRAS mutations, Tarceva alone tended to control cancer progression better than combined therapy, highlighting the importance of biomarker testing to identify which patients are most likely to benefit from different therapies.