MA04.07 Comparative Clinical Outcomes for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations

Abstract

Introduction: Non-cytotoxic therapy has changed the treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients and significantly improved outcomes. As survival outcomes continue to improve, quality of life (QOL) has become an important measure of success, and QOL analysis is increasingly being incorporated in clinical trial design. The objective of this systematic review was to assess the methodological quality of QOL analysis in NSCLC Randomized Clinical Trials (RCTs) involving biologic agents to treat NSCLC. Additionally, we assessed whether QOL measures included specific tools for neurological and cognitive measures for patients with central nervous system (CNS) involvement. Methods: A systematic literature search was performed using Medline, Embase, and Web of Science databases to identify NSCLC RCTs published between January 1 st ,1996 and January 10 th , 2020 reporting Quality of Life (QOL) measures. Only RCTs that both enrolled previously untreated patients with advanced NSCLC and had QOL analysis were included. Full-text analysis and data extraction was performed in duplicate. The CONSORT-PRO Extension checklist was used to evaluate the quality of included trials. Results: 4,439 abstracts were screened, of which only 96 RCTs met inclusion and exclusion criteria for analysis. 41,927 patients were enrolled in the included trials. The majority of trials included patients with treated brain metastases, but only 19 RCTs (8,444 patients) specified the incidence of CNS metastases at baseline with a median proportion of 11.57% (IQR 9.2 -23.2%). 33 trials involved biologic agents irrespective of tumor mutational status, and 17 studies only included patients that harbored a targetable mutation. The QOL assessment tools that were most commonly applied were EORTC-QLQ-LC13 (43 RCTs) and EORTC-QLQ-C30 (55 RCTs). The median number of verified CONSORT-PRO Extension criteria in the included trials was 3, and only in 10 trials were all 6 criteria well-documented. The least verified criteria were the following: report of statistical approaches for missing data (27 RCTs) and the discussion of limitations for QOL generalizability to clinical practice (41 RCTs). Only 13 RCTs performed subgroup analyses to specifically evaluate QOL. Better methodological quality of QOL reporting, defined by the number of fulfilled CONSORT-PRO Extension criteria, was observed in trials that included and specified the incidence of CNS metastases at baseline (p¼0.046) and in studies that only included patients with targetable mutations (p¼0.02) Conclusion: Considering the improving survival of lung cancer patients, more efforts should be pursued to analyze QOL in these patients. Further developing, standardizing, and implementing specific tools to analyze QOL is necessary to reflect the real-life experience of lung cancer patients in the era of personalized medicine.

Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations who progressed after platinum-based chemotherapy

“…With standard treatment options, patients with advanced NSCLC harboring EGFR ex20ins have poor prognoses, with a median OS of approximately 16 months. 14,36 The standard of care for these patients is platinum-based chemotherapy; however, all patients will eventually experience disease progression, with limited treatment options in subsequent LOT. 2,7,11,36 In a real-world analysis, median OS was 12.5 months and median PFS was 3.5 months in the relapsed setting, 37 emphasizing the high unmet need associated with EGFR ex20ins advanced NSCLC.…”

“…14,36 The standard of care for these patients is platinum-based chemotherapy; however, all patients will eventually experience disease progression, with limited treatment options in subsequent LOT. 2,7,11,36 In a real-world analysis, median OS was 12.5 months and median PFS was 3.5 months in the relapsed setting, 37 emphasizing the high unmet need associated with EGFR ex20ins advanced NSCLC. Amivantamab, the first treatment approved by the FDA for patients with advanced NSCLC harboring EGFR ex20ins whose disease progressed on or after platinum-based chemotherapy, 20 is a new targeted therapy in the treatment armamentarium for these patients.…”

Clinical Validation of Companion Diagnostics for the Selection of Patients with Non–Small Cell Lung Cancer Tumors Harboring Epidermal Growth Factor Receptor Exon 20 Insertion Mutations for Treatment with Amivantamab

“…This is especially important for molecularly heterogenous mutations such as EGFR ex20ins, which have over 100 unique variants identified. 28 The study was limited by the small number of samples, necessitating the inclusion of samples from supplementary populations. Matched negative plasma and tumor tissue samples were not available to directly test concordance between the CDxs.…”

An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical Practice in Europe and the United States for Patients with Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 Insertion Mutations

“…For example, realworld evidence demonstrates that patients with EGFR Exon20ins have a 75% increased risk of death and a 93% increased risk of disease progression or death compared with patients with common EGFR mutations [6]. This poorer prognosis may be attributed to a previous lack of effective, targeted treatments in the EGFR Exon20ins population and because EGFR Exo-n20ins may be associated with insensitivity and resistance to currently available EGFR-targeted treatments (such as EGFR tyrosine kinase inhibitors [TKIs)] [1,[6][7][8].…”