The real-world treatment patterns for patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions are diverse, according to a retrospective observational study, and underscore an unmet need for better treatment options for this patient population. EGFR exon 20 insertion mutations occur in 4% to 12% of all EGFR- mutated NSCLC cases. However, no targeted therapy is currently approved for this population. Patients with this cancer type are typically treated with front-line platinum-based chemotherapy. Novel therapies like mobocertinib are currently in development to treat EGFR exon-20 insertion-mutated NSCLC. Real-world treatment pattern information is limited. Immuno-oncology therapy has historically been considered an available therapy, but its effectiveness has yet to be established. The retrospective analysis used data from the Flatiron Health database with a data cut-off of February 29, 2020. Data were collected from approximately 800 sites of care. Four separate cohorts were included in the study totaling 237 patients. Cohort 1 included 129 patients receiving first-line (1L) therapy after documented EGFR exon 20 insertion mutations. Cohort 2 included 114 patients receiving second-line therapy or greater (≥2L). Cohort 3 included 63 patients with baseline characteristics in line with the eligibility criteria of part 3 of the mobocertinib trial (NCT02716116) who are on their ≥2L. Cohort 4 included 50 trial-aligned patients who were on their ≥2L therapy who were previously treated with platinum-based chemotherapy. End points of the study included treatment patterns for this patient population and the anti-tumor effectiveness of various treatment strategies assessed through the confirmed real-world overall response rate (rwORR), real-world progression-free survival (rwPFS), and overall survival (OS). Baseline characteristics were assessed within 3 months prior to index date entry. Treatment types were reported by using percentages and frequencies and the Kaplan-Meier method was used to estimated median OS and rwPFS with a corresponding confident interval of 95%. In total, 129 patients from 1L were included in the baseline characteristics analysis. The median age of patients in the 1L cohort was 66. In the 1L cohort, 65.1% of patients were female, 7% were Asian, 51.2% had a smoking history, 95.3% had adenocarcinoma, and 29.5% had brain metastasis. The ECOG performance status of this cohort varied with 51.2% of patients have a score between 0-1, 5.4% having a score of 2-3, and 43.4% did not have a reported score. The median time from initial diagnosis was 1.46 months for the 1L cohort. Patient characteristics were similar among the 3 cohorts that included patients with 2 or greater lines of therapy, with 50 patients from all 3 cohorts being included in the analysis. The median age for patients in the ≥2L cohort was 64. Sixty-eight percent of patients in this cohort were women, 8% were Asian, 42% had a history of smoking, 98% had adenocarcinoma, and 34% had brain metastasis. Over half, 58%, of patients in these cohorts had an ECOG performance status of 0-1 while the remaining 42% did not have a reported ECOG performance status. The median time from initial diagnosis was 11.14 months. Among all 4 cohorts, 96% had 1 prior line of therapy. Two percent had 2 prior lines and 2% had ≥3L of therapy. For the treatment pattern analysis, 129 patients from 1L were included and 50 patients from the ≥2L cohorts were included. In the 1L cohort, 28.7% of patients had received an EGFR tyrosine kinase inhibitor (TKI) compared to 20% in the ≥2L cohorts. Only 1 patient, amounting to 0.8% of the 1L population, received an EGFR TKI plus monoclonal antibodies. No patients in the ≥2L cohorts received this therapy. Less than 10%, 8.5%, of patients in the 1L cohort received immuno-oncology therapy while 40% in the ≥2L cohorts received this therapy. Chemotherapy other than platinum-based chemotherapy was administered to 2.3% of the 1L cohort compared to 14% in the ≥2L cohort. Other chemotherapy and monoclonal antibodies were administered to 0.8% of the 1L cohort compared to 8% of patients in the ≥2L cohorts. Platinum chemotherapy alone was administered to 0.8% of patients in the 1L cohort. No patient in the ≥2L cohorts received this therapy. Platinum chemotherapy in combination with other chemotherapy was administered to 31% of patients in 1L and 10% of patients in the ≥2L cohorts. A combination of platinum therapy, other chemotherapy, and immuno-oncology therapy was given to 12.4% of patients in the 1L cohort and 6% of patients in the ≥2L cohorts. Platinum chemotherapy, other chemotherapy, and monoclonal antibodies were given to 12.4% of patients in IL and 2% of patients in ≥2L. Overall, the study found that despite having available IO options, platinum-based chemotherapy alone or in combination with other therapy was the most common 1L treatment. Further, IO therapy administered alone or in a combination regimen appeared less effective for the subset of patients with EGFR exon 20 insertions. The rwORR was poor in every cohort, but especially for the ≥2L cohorts. The confirmed rwORR was 18.6% (12.3%-26.4%) for 1L (N=129). For cohort 2 (N=114), the rwORR was 9.6% (4.9%-16.6%). For cohort 3 (N=63) the rwORR was 11.1% (4.6%-21.6%). For cohort 4 (N=50), it was 14% (5.8%-26.7%). rwPFS and OS followed similar patterns. For cohort 1, the rwPFS was 5.2 months (3.1-6.9) and the OS was 17 months (11.2-19.5). For cohort 2, the rwPFS was 3.7 months (2.7-5.2) and the OS was 13.6 months (8.2-15.4). For cohort 3, the rwPFS was 3.4 months (2.5-6.4) and the OS was 13.6 months (8.3-17.8). For cohort 4, the rwPFS was 3.3 months (2.3-5.9) and the OS was 11.5 months (7.9-16.6). Broken down by line of therapy, for the 41 patients in 1L who received platinum-based chemotherapy, the rwORR was 19.5% (95% CI, 8.8%-34.9%), the median OS was 17 months (95% CI, 10.5-33.2), and the median rwPFS was 5.7 months (95% CI, 3.0-10.9). Among the 16 patients being treated with 1L therapy who received a combination of platinum-based chemotherapy and immuno-oncology therapy, the rwORR was 18.8% (95% CI, 4,0%-45.6%), the median OS was 11.3 months (95% CI, 5.6 to not reached [NR]), and the median rwPFS was 4.5 months (95% CI, 1.2-10.3). For the 11 patients in 1L who received immuno-oncology monotherapy, the rwORR was 9.1% (95% CI, 0.2%-41.3%), the median OS was 11 months (95% CI, 1.2-NR), and the rwPFS was 3.1 months (1.1-5.2). The 37 patients in 1L who received an EGFR TKI had an rwORR was 2.7% (95% CI, 0.1%-14.2%), the median OS was 10.7 months (95% CI, 3.4-22.3) and the rwPFS was 3.3 months (95% CI, 2.2-6.6). The rwORR for the 20 patients in the ≥2L post-platinum cohort who received immuno-oncology as monotherapy was 5% (0.1%-24.9%). The group has a median OS was 7.1 months (95% CI, 2.5-10.1) and the rwPFS was 2.2 months (95% CI, 1.7-3.0). Finally, for the 10 patients in the ≥2L post-platinum chemotherapy group who received an EGFR TKI, the rwORR was 10% (95% CI, 0.3%- 44.5%), the median OS was 12.2 months (95% CI, 1.3-17.8), and the rwPFS was 3.4 months (95% CI, 0.0-5.9). Of the 13 patients treated in 1L or ≥2L, notably, no patients had a confirmed response to osimertinib (Tagrisso). According to the study investigators, limitations of the study include collected in the real-world setting may not be uniform, the small sample size, and the discrepancies between the community and academic settings. REFERENCE: Ou S, Lin H, Hong J, et al. Real-world response and outcomes in non-small cell lung cancer patients with epidermal growth factor receptor exon 20 insertion mutations. J Clin Oncol. 2021; 39 (suppl 15): 9098-9098. doi: 10.1200/JCO.2021.39.15_suppl.9098