Patterns of Failure in Metastatic Non-Small Cell Lung Cancer Patients After Initiation of Pembrolizumab.

PURPOSE/OBJECTIVE(S) To retrospectively investigate the patterns of failure and potential benefits of local therapy for patients with metastatic non-small cell lung cancer (NSCLC) receiving immunotherapy. MATERIALS/METHODS This single institution, retrospective analysis included 118 patients diagnosed with stage IV NSCLC from January 2015 to May 2020 who received at least one cycle of pembrolizumab, with or without concurrent chemotherapy, and had radiographic follow up of at least 3 months. Patterns of failure were identified by first disease progression event after initiation of immunotherapy. Progression was defined by radiographic evidence of tumor growth and/or development of new sites of disease. Failure events were grouped into the following categories: local, regional, distant, or combined (any combination of synchronous local, regional, or distant disease progression). Overall survival (OS), progression-free survival (PFS) and time to treatment failure (TTF) were calculated using the Kaplan-Meier method. RESULTS The median follow up time for the 118 patients included in the analysis was 8.5 months. Overall, 70 patients (59.3%) developed progression of disease while on immunotherapy. Of these, 15 (12.7%) progressed locally alone, 2 (1.7%) progressed regionally alone, 17 (14.4%) progressed distantly alone, and the majority (36 (30.5%)) experienced a combined progression. Of the 36 patients who developed synchronous combined progression, 31 (86.1%) shared distant failure with either a local and/or regional failure. The median OS, PFS, and TTF for the entire cohort were 15.8 months, 6.3 months, and 7.3 months respectively. When stratified by patterns of failure, the median OS for local, regional, distant, combined and no progression were 12.4, 18.3, 13.5, 10.7, and 41.7 months respectively (P = 0.024). The median PFS for the same groupings were 3.5, 16.8, 4.2, 3.5, and 41.7 months respectively (P < 0.0001). Of the 41 patients with only local progression or a combination of local and another site of progression, 18 received extracranial radiation concurrently with pembrolizumab (12 palliative RT, 6 consolidative SBRT). There was a statistically significant improvement in OS for this cohort of patients (any local progression) favoring those who received radiation concurrently with immunotherapy (15.8 vs 8.7 months; P = 0.039), but there was no PFS benefit (P = 0.098). CONCLUSION Approximately 60% of patients in this retrospective analysis experienced progression of disease after initiation of pembrolizumab. The most common pattern of failure was a combination of local, regional, and/or distant progression. Additional study of the potential benefits of adding local therapy (radiation) to immunotherapy for these patients is warranted.