Patterns of second-line treatment in patients with NSCLC and targetable mutations.

e20699 Background: Several studies suggest that up to 30% of patients with non-small cell lung cancer (NSCLC) do not receive second-line systemic therapy. Characterizing the patterns of second-line treatment in patients with NSCLC and targetable mutations may help identify barriers to treatment and improve patient outcomes. Methods: We retrospectively collected data from patients with metastatic NSCLC and a targetable mutation, who were seen at MedStar Georgetown University Hospital after January 1st, 2018. Results: We identified 197 eligible patients for the study. Of these, 80 (41%) had a classical EGFR mutation, 11 (6%) had an EGFR exon 20 insertion, 9 (5%) had atypical or compound EGFR mutations, 25 (13%) had an ALK fusion, 22 (11%) had a KRAS G12C mutation, 11 (6%) had a ROS1 fusion, 13 (7%) had a HER2 mutation, 10 (5%) had a RET fusion, 4 (2%) had a MET exon 14 skipping mutation, 11 (6%) had a BRAF V600E mutation, and 2 (1%) had an NRG1 fusion. At the time of data collection, 47 patients (24%) had not progressed on first-line therapy. Of the 150 patients who discontinued first-line treatment, 121 (81%) received second-line therapy, with no differences observed in the receipt of second-line therapy across mutation types (p = 0.14). The median time from second-line to third-line systemic therapy was 6 months. The most common second-line treatment was other targeted therapy (N=46, 38%), followed by chemotherapy ± original targeted therapy (N=30, 25%), a clinical trial (N=29, 24%), chemoimmunotherapy (N=10, 8%), immunotherapy (N=3, 2%), and other treatments (N=3, 2%). Of the 29 patients (19%) who discontinued first-line therapy without receiving second-line treatment, 27 (93%) either passed away or transitioned to hospice, and 2 (7%) were lost to follow-up. Patients who discontinued first-line therapy without receiving second-line treatment were older, with a median age of 69, compared to a median age of 62 in those who received second-line treatment (p < 0.01). Of the 27 patients who died, 22 (81%) transitioned to hospice due to disease progression or cancer-related complications, 2 (7%) died from poor treatment tolerance or toxicity, and 3 (11%) died from other or unknown causes. Conclusions: While most patients receive second-line treatment, a subset do not. This is primarily due to death or transition to hospice, which are mostly due to disease progression or cancer-related complications. The findings emphasize the importance of optimizing first-line treatment strategies and the need to address barriers to second-line treatment.