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.