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

Abstract

e21674 Background: 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 in order to help guide effective use of targeted radiation therapy to sites of gross disease most likely to progress. Methods: This single center, retrospective study included all patients diagnosed with Stage IV NSCLC between June 2015 and February 2019 who received at least 2 cycles of nivolumab, pembrolizumab, or atezolizumab, with or without concurrent chemotherapy. Immune RECIST criteria were used to assess patterns of disease progression, and progression-free survival (PFS), excluding irradiated tumors. Descriptive statistics were used to report baseline patient and tumor characteristics. The Chi square and log-rank tests were used to determine whether any baseline clinical characteristics were associated with progressive disease in initial sites only (vs. new or combined sites), and PFS, respectively. Factors assessed included initial metastatic sites, tumor histology, performance status, PD-L1 expression, untreated primary tumor, history of brain metastasis, number of metastatic sites involved, and use of concurrent chemo-immunotherapy. 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 tumor location were higher for liver (64%) and lung metastases (61%) than for other metastatic sites (33-36%) or the primary tumor (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 tumor (72% vs. 56%, p= 0.169). Conclusions: The dominant pattern of disease progression for patients with metastatic NSCLC on checkpoint inhibitor immunotherapy is in the initial sites of disease alone, whereas only 10% of patients progressed in new disease site(s) alone, suggesting a potential role for local radiation therapy as a complementary treatment modality. Pre-treatment patient and tumor characteristics did not predict patients most likely to benefit.