Impact of EML4-ALK Variants and Co-Occurring TP53 Mutations on Duration of First-Line ALK Tyrosine Kinase Inhibitor Treatment and Overall Survival in ALK Fusion-Positive NSCLC: Real-World Outcomes From the GuardantINFORM database.

Introduction: Tyrosine kinase inhibitors (TKIs) are first-line treatment options for ALK-positive (ALK+) NSCLC. Factors such as variant allele frequencies (VAFs), EML4-ALK fusion variant, and concurrent TP53 mutations (TP53mt) in circulating tumor DNA (ctDNA) may affect treatment outcomes. We evaluated their effects on time to discontinuation (TTD) of first-line treatment with next-generation ALK TKIs in a real-world setting.

Real-World Treatment Patterns and Outcomes Across Three Lines of Therapy in Patients with ALK+ NSCLC.

Introduction: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are standard first- and second-line treatment for advanced ALK+ non-small cell lung cancer (NSCLC). We evaluated outcomes in patients with ALK+ NSCLC receiving third-line ALK TKI versus non-ALK-directed therapy.

Methods: Flatiron Health OncoEMR data were extracted for patients with ALK+ NSCLC initiating first-line ALK TKI between January 2015 and March 2022 followed by second-line ALK TKI and third-line ALK TKI (group A) or non-TKI therapy (group B).

Demonstration of 10 nm Ferroelectric AlScN-Based Capacitors for Enabling Selector-Free Memory Array.

In this work, 10 nm scandium-doped aluminum nitride (AlScN) capacitors are demonstrated for the construction of the selector-free memory array application. The 10 nm AlScN film deposited on an 8-inch silicon wafer with sputtering technology exhibits a large remnant polarization exceeding 100 µC/cm and a tight distribution of the coercive field, which is characterized by the positive-up-negative-down (PUND) method. As a result, the devices with lateral dimension of only 1.

Efficacy of Mobocertinib and Amivantamab in Patients With Advanced Non-Small Cell Lung Cancer With EGFR Exon 20 Insertions Previously Treated With Platinum-Based Chemotherapy: An Indirect Treatment Comparison.

Introduction: Exon 20 insertions (ex20ins) mutations of the EGFR gene account for 1% to 2% of all non-small-cell lung cancers (NSCLCs). Targeted therapies have been developed to treat this cancer type but have not been studied in head-to-head trials. Our objective was to use a matching-adjusted indirect comparison (MAIC) to assess the efficacy of mobocertinib and amivantamab in patients with NSCLC EGFR ex20ins mutations who were previously treated with platinum-based chemotherapy.

Establishing Meaningful Change Thresholds in Patient-Reported Outcomes Among Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in ALTA-1L Trial.

Objectives: An earlier study from the ALTA-1L trial of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer demonstrated that brigatinib produces superior health-related quality of life (QoL) outcomes over crizotinib. This study aimed to derive meaningful change thresholds (MCTs) for European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 to refine the earlier results.

Methods: Patients from the ALTA-1L trial were administered the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires.

Real-World Response and Outcomes in Patients With NSCLC With Exon 20 Insertion Mutations.

Introduction: This study describes treatment patterns and outcomes in patients with NSCLC with EGFR exon 20 insertions () in the United States.

Methods: The Flatiron Health electronic health record database was used to select three cohorts among patients diagnosed with NSCLC with (January 1, 2011-February 29, 2020): (1) first-line (1L) or patients receiving 1L therapy after documented ; (2) second or later-line (≥2L) or patients receiving ≥2L therapy after documented ; and (3) ≥2L postplatinum trial-aligned, or ≥2L patients previously treated with platinum chemotherapy whose baseline characteristics aligned with key eligibility criteria (initiating new treatment after documented and ≥1 previous treatment excluding mobocertinib or amivantamab) of the mobocertinib trial NCT02716116. Real-world end points were confirmed overall response rate, overall survival, and progression-free survival.

Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial.

Introduction: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib.

Methods: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-d lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS).

Real-world evidence in lung and hematologic oncology health technology appraisals: a review of six assessment agencies.

To assess the use and acceptability of real-world evidence (RWE) in lung and hematologic cancer appraisals. A review of appraisals published by National Institute for Health and Care Excellence (NICE) in the UK was conducted. A total of 20 case studies employing RWE were identified and compared across five additional health technology assessment agencies: Scottish Medicines Consortium (SMC) (Scotland), CADTH (Canada), INESSS (Quebec), HAS (France) and IQWiG (Germany).

Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison.

Introduction: Mobocertinib is a novel, first-in-class, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) designed to selectively target in-frame EGFR exon 20 insertions (ex20ins). Comparative effectiveness data for mobocertinib versus real-world treatments are lacking in this rare population. This study compared data for mobocertinib reported in a Phase I/II single-arm clinical trial with an external control group consisting of patients who received available treatment in the real-world setting in the United States (US).

Indirect comparison of mobocertinib and real-world therapies for pre-treated non-small cell lung cancer with EGFR exon 20 insertion mutations.

Objectives: Mobocertinib, a novel oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is available for the treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations after platinum chemotherapy. We performed an indirect comparison of clinical trial data and real-world data (RWD) to determine the relative efficacy of mobocertinib vs. other treatments for these patients.

Distribution and Detectability of EGFR Exon 20 Insertion Variants in NSCLC.

Introduction: EGFR exon 20 insertion (ex20ins) mutations represent 5% to 10% of EGFR mutations in NSCLC. Identifying patients with EGFR ex20ins is challenging owing to the limited coverage of polymerase chain reaction (PCR) assays and the relatively recent use of next-generation sequencing (NGS). This study analyzes the spectrum of EGFR ex20ins variants in a large patient population from a global clinical trial and several real-world cohorts and the ability of PCR kits to identify these alterations.

Mobocertinib (TAK-788) in Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort.

Mobocertinib, an oral, first-in-class epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for exon 20 insertions (ex20ins), achieved durable responses in adults with previously treated ex20ins+ metastatic non-small cell lung cancer (mNSCLC) in the EXCLAIM extension cohort of a phase 1/2 study (N = 96; NCT02716116). We assessed patient-reported outcomes (PROs) with mobocertinib 160 mg once daily (28-day cycles) in EXCLAIM (N = 90) with the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30) v3.0, lung cancer module (QLQ-LC13), EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire, and selected PRO Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire.

Identifying symptomatic adverse events using the patient-reported outcomes version of the common terminology criteria for adverse events in patients with non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations.

Objective: Tolerability and safety of treatments are important in oncology trials and should be informed by patient assessments. We identified the most relevant patient-reported symptomatic adverse events (AEs) to measure in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

Methods: This study selected relevant symptomatic AEs from 78 AEs available in the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system.

Real-world ALK Testing Trends in Patients With Advanced Non-Small-Cell Lung Cancer in the United States.

Introduction: Patients with non-small-cell lung cancer (NSCLC) whose tumors harbor anaplastic lymphoma kinase (ALK) rearrangements can be treated with ALK tyrosine kinase inhibitors. We assessed real-world ALK biomarker testing and treatment patterns of patients with NSCLC in the United States.

Patients And Methods: Data were extracted from the Flatiron Health electronic health record-derived deidentified database for patients aged ≥18 years with stage IIIB or IV NSCLC and ≥2 clinic visits between January 2011 and December 2019.

Economic burden in patients with anaplastic lymphoma kinase ()-positive non-small cell lung cancer (NSCLC), with or without brain metastases, receiving first-line ALK inhibitors.

Introduction: This observational study describes the real-world economic burden in patients with anaplastic lymphoma kinase () positive non-small cell lung cancer (NSCLC) receiving a first-line ALK inhibitor, and the economic impact of brain metastases (BM).

Methods: Administrative claims data (Truven Health MarketScan® Commercial Claims and Encounters database and Medicare Supplemental and Coordination of Benefits database; January 1, 2015-March 31, 2020) for adult patients with + NSCLC who received a first-line ALK inhibitor were retrospectively reviewed. Healthcare costs and resource utilization were calculated on a per-patient-per-month (PPPM) basis and stratified by the presence or absence of BM prior to first-line ALK inhibitor.

Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2).

Introduction: Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor approved for treatment-naive and crizotinib-refractory advanced ALK-positive (ALK+) NSCLC. We evaluated brigatinib after other next-generation ALK tyrosine kinase inhibitors.

Methods: In this single-arm, phase 2, ALK in Lung Cancer Trial of brigAtinib-2 (NCT03535740), patients with advanced ALK+ NSCLC whose disease progressed on alectinib or ceritinib received brigatinib 180 mg once daily (after 7-d 90-mg lead-in).

Real-World Efficacy and Tolerability of Brigatinib in Patients with Non-Small Cell Lung Cancer with Prior ALK-TKIs in the United States.

Background: Real-world evidence for brigatinib, a next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) used in ALK-rearranged non-small cell lung cancer, is scarce. This retrospective study evaluated real-world brigatinib utilization in the US post other ALK-TKIs.

Materials And Methods: Adults with ≥1 brigatinib claim (index date) between 1 April 2017 and 30 September 2020 in the IQVIA longitudinal pharmacy claims database were followed until dose reduction, discontinuation, or end of follow-up.

Non-small cell lung cancer with exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes.

Introduction: exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC) is rare, has a poor prognosis, and outcomes are not fully established. We describe and evaluate outcomes from real-world and clinical evidence in these patients.

Methods: A systematic literature review (SLR) identified interventional and real-world evidence (RWE) studies reporting clinical outcomes for exon 20 insertion mutation-positive NSCLC.

Indirect comparisons of brigatinib and alectinib for front-line -positive non-small-cell lung cancer.

To conduct an indirect treatment comparison (ITC) of the relative efficacy of brigatinib and alectinib for progression-free survival in people with tyrosine kinase inhibitor (TKI)-naive -positive non-small-cell lung cancer (NSCLC). Final aggregate and patient-level data from the ALTA-1L trial comparing brigatinib to crizotinib and published aggregate data from ALEX (comparing alectinib to crizotinib) were contrasted using Bucher ITC and matching-adjusted indirect comparisons (MAICs). No statistically significant differences were identified between brigatinib and alectinib in reducing the risk of disease progression overall and in patients with baseline central nervous system metastases.

The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions.

Background: EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce.

Patients And Methods: We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.

Testing Patterns and Detection of Exon 20 Insertions in the United States.

Introduction: exon 20 insertions () are a diverse set of mutations in NSCLC that are refractory to tyrosine kinase inhibitors. We describe real-world detection patterns in patients with advanced NSCLC in the United States.

Methods: Data from 2011 to 2020 were extracted from the Flatiron Health electronic health record-derived deidentified database.

Flexible thin-film acoustic wave devices with off-axis bending characteristics for multisensing applications.

Flexible surface acoustic wave (SAW) devices have recently attracted tremendous attention for their widespread application in sensing and microfluidics. However, for these applications, SAW devices often need to be bent into off-axis deformations between the acoustic wave propagation direction and bending direction. Currently, there are few studies on this topic, and the bending mechanisms during off-axis bending deformations have remained unexplored for multisensing applications.

Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial.

Importance: Metastatic non-small cell lung cancer (mNSCLC) with EGFR exon 20 insertion (EGFRex20ins) mutations is associated with a poor prognosis. Mobocertinib is an oral tyrosine kinase inhibitor designed to selectively target EGFRex20ins mutations.

Objective: To evaluate treatment outcomes and safety of mobocertinib in patients with previously treated EGFRex20ins-positive mNSCLC.