Patterns of disease progression to checkpoint inhibitor immunotherapy in patients with stage IV non-small cell lung cancer.

INTRODUCTION The purpose of this study was to assess patterns of disease progression for patients with metastatic non-small cell lung cancer (NSCLC) on checkpoint inhibitor immunotherapy. METHODS This single centre, retrospective study included all patients diagnosed with Stage IV NSCLC from 2015 to 2019 who received at least 2 cycles of immunotherapy, with or without concurrent chemotherapy. Immune RECIST criteria were used to assess patterns of disease progression, and progression-free survival (PFS), excluding irradiated tumours. The chi-square and log-rank tests assessed for associations between baseline clinical characteristics and progressive disease in initial sites only (vs. new or combined sites), and PFS, respectively. RESULTS Among 143 eligible patients with a median follow-up of 11 months, 97 (68%) developed disease progression. Of these, 67 patients (69.1%) progressed only at initial disease site(s), 10 patients (10.3%) progressed only at new disease site(s), and 20 patients (20.6%) progressed in both initial and new sites. Rates of disease progression based on tumour location were higher for liver (64%) and lung metastases (61%) than for other metastatic sites (33-36%) or the primary tumour (24%). Only higher PD-L1 expression (P = 0.002) and absence of lung metastasis (P = 0.048) at baseline were associated with improved PFS. No baseline characteristics significantly impacted the probability of initial disease site-only progression, though a trend was observed for untreated primary tumour (72% vs. 56%, P = 0.169). CONCLUSIONS The dominant pattern of disease progression is in the initial sites of disease alone, suggesting a potential role for local radiation therapy as a complementary treatment modality to immunotherapy.