Polytherapy Beats Monotherapy as Second-Line Treatment for NSCLC

Combining targeted therapy improves overall survival for patients with non-small cell lung cancer (NSCLC), compared to using the targeted drug erlotinib (Tarceva) alone, according to a recent study. By pooling data from eight clinical trials, researchers found that patient outcomes were improved when combination therapy was used as a second-line treatment for NSCLC.

Patients with advanced NSCLC who have already received initial therapy usually take erlotinib alone as a second-line treatment. Erlotinib directly targets the EGFR protein and can be particularly effective for patients with mutations in the EGFR gene.

Despite good responses in some patients, erlotinib monotherapy has limited efficacy and alternatives are needed. However, stage II and III trials of treatments that combine targeted therapies have not demonstrated improved overall survival compared with erlotinib alone, perhaps due to small sample sizes.

In the new study, a larger sample size was used to increase statistical power. Wei-Xiang Qi of Shanghai Jiao Tong University in Shanghai, China, and colleagues performed a meta-analysis that combined the published data of 2,417 patients. They found longer overall survival and longer progression-free survival, as well as better overall response rate, in patients who had received combination therapies as second-line NSCLC treatment.

While progression-free survival was higher in the combination therapy groups, erlotinib monotherapy was actually more beneficial for patients with EGFR mutations or wild-type (non-mutated) KRAS. Although expressed by only a small fraction of the total patient cohort, these and other molecular markers may be predictive of therapy outcome. Erlotinib, for example, could benefit patients differently depending on other combination treatment agents and tumor mutation type. With respect to adverse events, patients receiving combination therapies had more instances of rash, fatigue, and high blood pressure, while diarrhea and anemia were found to occur just as frequently with erlotinib monotherapy as with combination therapy.

The combination therapies tested in the eight trials differed, but all included erlotinib-based doublet therapy plus a targeted agent such as bortezomib, everolimus, bevacizumab, R1507, tivantinib, sorafenib, sunitinib, or entinostat. On their own, each of the eight trials failed to find survival benefits of these combined therapies. The results underscore the fact that NSCLC is a heterogeneous disease and one size does not fit all when it comes to combination treatments.

Though this meta-analysis cannot determine which of the combination treatment regimens would be the best choice for advanced NSCLC, it does indicate that targeting multiple cancer signaling pathways could have synergistic effects and increased clinical benefit for patients. More research is needed to identify the combination treatments, and treatment durations, that best target different NSCLC tumor types. This study was published in the journal PLoS One.