In early 2018, the PACIFIC trial regimen was approved by the US Food and Drug Administration before many immune checkpoint inhibitors (ICIs) were approved for first-line treatment of metastatic non–small cell lung cancer (NSCLC).¹ In this trial, patients with unresectable stage III NSCLC received durvalumab for 1 year after chemoradiation therapy (CRT). This changed the disease’s paradigm with a considerably improved overall survival. However, no further research in this space had occurred until more recently; the once very debated stage III disease was dormant when advances were occurring in early-stage and genomic-driven NSCLC.

Intending to improve the outcomes of patients with NSCLC, oncologists keep trying to answer the same question: is adding more ICIs the solution? In this issue of JAMA Oncology, Ross et al² explore this concept by conducting a phase 2 trial that incorporated neoadjuvant atezolizumab before CRT, then consolidation chemotherapy for 2 cycles followed by atezolizumab for 1 year in patients with stage III unresectable NSCLC. Sixty-two patients received at least 1 cycle of therapy. The disease control rate (DCR) at 12 weeks was 74.2%, with a median progression-free survival (PFS) of 30.0 months. At the time of data cutoff, the median overall survival (OS) had not been reached. However, OS at 24 months was 73.7%. The study actively recruited patients in racial and ethnic minority groups, with 14.5% self-identifying as Black, which is to my knowledge the highest representation in any early-stage or unresectable NSCLC trial. The authors also incorporated correlative studies. However, programmed cell death 1 ligand 1 levels did not correlate significantly with DCR, PFS, or OS, showing the inaccuracy of the marker, particularly when radiation is added to the equation. As the trial progressed, fewer patients were able to get therapy, with 71.0% of patients completing CRT and only 41.9% completing all study therapies—attributed to the many phases of treatment in the trial.