Abstract
The PACIFIC trial of durvalumab administered for 1 year to patients with stage III lung cancers has set a new standard of care. PACIFIC established the role of immune checkpoint inhibitors (ICIs) for individuals with inoperable and unresectable locally advanced lung cancers that achieve disease control from concurrent chemoradiation. For patients with resectable and operable disease, ICIs administered before surgery, either alone (JHU/MSK, LCMC3, and NEOSTAR) or in combination with chemotherapy (Columbia/MGH and NADIM), have yielded high rates of major pathologic response in resection specimens, an outcome measure that correlates with improved progression-free survival and overall survival. These results have brought forth the dilemma of how to choose the optimal local therapy-either definitive concurrent chemoradiation or surgery-to use with an ICI for patients with stage III lung cancers that are both operable and resectable. Here, we review the data that support the use of each local therapy. Recent successes have also raised the possibility that using ICIs in patients with earlier stages of lung cancer will enhance curability. Randomized trials are underway; however, until they read out, physicians must choose between local and systemic therapies on the basis of the information we have today. Research demonstrates that using surgery, radiation, chemotherapy, and ICIs improve all efficacy outcomes and curability. All modalities should be considered in every patient with locally advanced lung cancer. It is imperative that a multimodality discussion that includes the possible addition of ICIs takes place to choose the best modality and sequence of therapies for each patient.