Neoadjuvant treatment of stage IIIA-N2 in EGFR-Mutant/ALK-rearranged non-small cell lung cancer

Defining the optimal neoadjuvant strategy in early-stage and locoregional (N2) oncogenic-driven lung cancer remains a major challenge for the scientific community. Whereas significant advances have been achieved with the use of personalized medicine and targeted therapies in advanced stages, we are still far from translating the same magnitude of benefits into an earlier-stage disease. Perioperative strategies with neoadjuvant and adjuvant tyrosine kinase inhibitors in patients with EGFR and ALK gene alterations have yielded mixed results and further biomarker-driven trials are needed to shed more light on the significance of inhibiting the oncogenic signaling addiction at earlier stages of the disease and the conceivable value of incorporating more potent targeted inhibitors in this setting. Meanwhile, the landscape of early-stage lung cancer management is progressing rapidly, and we anticipate the incorporation of novel immunotherapeutic agents on the basis of this promising preliminary activity as induction strategies. Whether the benefits observed in the overall population can be translated into specific subsets of oncogenic-driven tumors is still unknown, but it clearly reinforces the importance of incorporating—sooner rather than later—a biomarker-testing strategy into the routine work-up of early-stage non-small cell lung cancer (NSCLC). There are still many challenges to overcome such as the need to stablish standardized surrogate endpoints and to define the optimal duration of perioperative treatment, as well as how to expedite patient recruitment using enrichment strategies for biomarker stratified trials. Despite the difficulties, we are living in exciting times and coming up on a new window of opportunities for achieving the ultimate goal of curing early-stage lung cancer and improving long-term outcomes by eliminating the minimal residual disease and reducing the risk for metastatic recurrence.