This study described treatment patterns, healthcare resource utilization (HRU) and costs among advanced or metastatic non-small cell lung cancer (a/mNSCLC) patients with different epidermal growth factor receptor (EGFR) mutation types. This retrospective study leveraged NeoGenomics NeoNucleus™ linked with IQVIA PharMetrics® Plus between 01Jan2016 to 30Apr2021 (study period). Patients with evidence of a/mNSCLC between 01Jul2016 to 31Mar2021 (selection window) with EGFR test results indicating exon 19 deletion (exon19del), exon 21 L858R (L858R), or exon 20 insertion (exon20i) mutations were included; date of first observed evidence of a/mNSCLC was the index date. Treatment patterns, all-cause HRU and costs during ≥1 month follow-up were reported for each cohort (exon19del, L858R, and exon20i). A total of 106 exon19del, 75 L858R, and 13 exon20i patients met the study criteria. The prevalence of hospitalization was highest in the exon20i cohort (76.9%), followed by L858R (62.7%) and exon19del (55.7%) cohorts. A higher proportion of patients had evidence of hospice/end-of-life care in the exon20i (30.8%) and L858R (29.3%) cohorts relative to the exon19del cohort (22.6%). The exon20i cohort had higher median total healthcare costs per patient per month ($27,069) relative to exon19del ($17,482) and L858R ($17,763). EGFR tyrosine kinase inhibitors (TKI) were the most frequently observed treatment type for exon19del and L858R cohorts, while chemotherapy was the most observed treatment in exon20i cohort. The sample size for the study cohorts was small, thus no statistical comparisons were conducted. This is one of the first real-world studies to describe HRU and costs among a/mNSCLC patients by specific EGFR mutation type. HRU and costs varied between EGFR mutation types and were highest among exon20i cohort, potentially reflecting higher disease burden and unmet need among patients with this mutation.

Treatment resistance due to gene alterations remains a challenge for patients with EGFR-mutated advanced or metastatic non-small-cell lung cancer (a/mNSCLC). A systematic literature review (SLR) was conducted to describe resistance mutation profiles and their impact on clinical outcomes in adults with a/mNSCLC in the United States (US). A comprehensive search of MEDLINE and Embase (2018–August 2022) identified 2986 records. Among 45 included studies, osimertinib was the most commonly reported treatment (osimertinib alone: 15 studies; as one of the treatment options: 18 studies), followed by other tyrosine kinase inhibitors (TKIs; 5 studies) and non-TKIs (1 study). For first-line (1L) and second-line (2L) osimertinib, the most frequent EGFR-dependent resistance mechanisms were T790M loss (1L: 15.4%; 2L: 20.5–49%) and C797X mutation (1L: 2.9–12.5%; 2L: 1.4–22%). EGFR-independent mechanisms included MET amplification (1L: 0.6–66%; 2L: 7.2–19%), TP53 mutation (1L: 29.2–33.3%), and CCNE1 amplification (1L: 7.9%; 2L: 10.3%). For patients receiving osimertinib, EGFR T790M mutation loss, EGFR/MET/HER2 amplification, RET fusion, and PIK3CA mutation were associated with worse progression-free survival. Resistance mechanisms resulting from current NSCLC treatments in the US are complex, underscoring the need to address such heterogeneous resistance profiles and improve outcomes for patients with EGFR-mutated a/mNSCLC.

Background: Recent clinical trials have demonstrated improved efficacy of combination regimens, including amivantamab plus lazertinib and osimertinib plus platinum-based chemotherapy, compared with standard therapy in patients with epidermal growth factor receptor (EGFR)–mutated non-small cell lung cancer (NSCLC). As these regimens enter routine clinical use, understanding the economic implications of treatment-related adverse event (AE) management, including proactive therapy management (PTM), is important. Objectives: To estimate and compare grade 3 or 4 AE management costs associated with first-line amivantamab (intravenous [IV] or subcutaneous [SC]) plus lazertinib and osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC from a US Commercial and Medicare Advantage payer perspective. Methods: A descriptive cost modeling analysis used grade 3/4 AE incidence data from pivotal clinical trials of amivantamab (IV and SC) plus lazertinib and osimertinib plus platinum-based chemotherapy. AEs occurring in ≥5% of patients or deemed clinically significant were included. PTM strategies for dermatologic events, venous thromboembolism, and infusion-related reactions were modeled for amivantamab-based regimens using guideline-concordant practices and clinical trial evidence. As a conservative assumption, PTM for osimertinib plus platinum-based chemotherapy was not included. AE management costs were derived from national inpatient and physician fee schedules and inflated to 2025 US dollars. Total per-patient AE management and PTM costs were estimated for each treatment regimen. Scenario analyses evaluated expanded PTM assumptions. Results: Across both payer perspectives, total AE management costs were estimated to be lower for amivantamab-based regimens than for osimertinib plus platinum-based chemotherapy. Under the Commercial perspective, modeled AE management costs were $2345 for amivantamab (SC) plus lazertinib, $4321 for amivantamab (IV) plus lazertinib, and $8497 for osimertinib plus platinum-based chemotherapy. Corresponding Medicare Advantage estimates were $1166, $2425, and $4185, respectively. Inclusion of PTM costs did not alter the relative cost ranking calculated and findings were consistent across scenario analyses. Conclusions: Results from this descriptive cross-trial analysis indicated that total AE management costs were consistently estimated to be lower in patients receiving amivantamab (SC or IV) plus lazertinib compared with osimertinib plus platinum-based chemotherapy across both a Commercial and Medicare Advantage payer perspective.