sj-docx-1-opp-10.1177_10781552221126174 - Supplemental material for Economic burden in patients with anaplastic lymphoma kinase (<i>ALK</i>)-positive non-small cell lung cancer (NSCLC), with or without brain metastases, receiving first-line ALK inhibitors

Supplemental material, sj-docx-1-opp-10.1177_10781552221126174 for Economic burden in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), with or without brain metastases, receiving first-line ALK inhibitors by Yanyu Wu, Kaili Ren, Yin Wan and Huamao M Lin in Journal of Oncology Pharmacy Practice</p

Immunotherapy Treatment Patterns and Outcomes Among ALK-Positive Patients With Non–Small-Cell Lung Cancer

The treatment landscape for anaplastic lymphoma kinase (ALK)-positive non–small-cell lung cancer (NSCLC) primarily involves ALK-directed tyrosine kinase inhibitors (TKIs). Although therapy with immune checkpoint inhibitors (ICIs) is a treatment option in NSCLC, the efficacy of ICI is inconclusive in ALK-positive NSCLC as a result of limited data. This retrospective real-world study sought to describe the characteristics of ALK-positive NSCLC patients treated with ICI and to assesses treatment outcomes in US oncology practices. This analysis used the Flatiron Health electronic health record–derived deidentified database and included adult (18 years and older) ALK-positive advanced NSCLC patients with receipt of one or more ICIs after January 1, 2015. Median time to ICI discontinuation and real-world progression-free survival (rwPFS) were estimated by Kaplan-Meier methods. Of 83 patients with ALK-positive NSCLC treated with ICIs, 50.6% (n = 42) received ICI without a prior ALK TKI. Median time to ICI discontinuation was 2.17 months (95% confidence interval, 1.41, 3.32). The median rwPFS was 2.34 months (95% confidence interval, 1.55, 3.09); in patients who received an ICI without prior ALK TKI, it was 3.9 months, and in patients who received ICI therapy after an ALK TKI, it was 1.5 months. Real-world effectiveness (rwPFS) of ICIs in ALK-positive NSCLC patients, whether provided before or after TKIs, was limited, underscoring the relative lack of efficacy of ICI in this patient population, particularly compared to approved ALK TKIs. The efficacy of immune checkpoint inhibitors (ICI) in ALK-positive non–small-cell lung cancer (NSCLC) is inconclusive as a result of limited data. We conducted a real-world analysis in 83 patients with ALK+ advanced NSCLC treated with ICI. The median real-world progression-free survival was 2.34 months from initiation of ICI therapy. The real-world effectiveness of ICI in ALK+ NSCLC patients was limited

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

Aims: To describe the real-world economic burden of patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) treated with post-crizotinib, second-line ALK inhibitor therapy. Materials and methods: Retrospective analysis using data from US Optum: Clinformatics Data Mart administrative claims database. Adult patients with ALK + NSCLC treated with ceritinib or alectinib as second-line ALK inhibitors between 1 January 2011 and 30 September 2017 were included. Healthcare costs and resource utilization for up to 1 year of therapy were calculated on a per-patient-per-month (PPPM) basis and stratified by presence or absence of brain metastases (BM). Multivariate regression analysis was performed to identify factors associated with costs. Top ten cost drivers of non-inpatient procedure costs were recorded. Results: One hundred and twelve patients received second-line ALK inhibitors. Total mean PPPM healthcare costs were $23,984 for all patients receiving up to 1 year of post-crizotinib, second-line ALK inhibitor therapy. Total mean PPPM costs for patients with BM on or prior to post-crizotinib, second-line ALK inhibitor therapy were 1.37-times as high as those for patients without BM (p = 0.0406). Mean PPPM outpatient visits and inpatient hospitalization stays were higher for patients with BM versus no BM. The main cost drivers for non-inpatient procedures were radiation therapy, medications, and diagnostic radiology. Limitations: Analyses did not include newer ALK-directed therapies. BM development after the index date (defined as the date of the first claim for a second-line ALK inhibitor) may have been misclassified as non-BM. Findings may not be generalizable to patients with no health insurance coverage. Conclusions: Treatment of patients with ALK + NSCLC with ceritinib or alectinib as post-crizotinib, second-line ALK inhibitor therapy represents a high economic burden. Healthcare costs and resource utilization were significantly higher for patients with ALK + NSCLC with BM versus no BM

Real‐World Treatment Patterns and Progression‐Free Survival Associated with Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non‐Small Cell Lung Cancer

Background Little is known about real‐world treatment and outcomes of patients with anaplastic lymphoma kinase‐positive (ALK+) advanced non‐small cell lung cancer (NSCLC). Patients and Methods This retrospective study of the Flatiron Health EHR‐derived deidentified database included patients with a lung cancer diagnosis and confirmed advanced NSCLC who received ALK tyrosine kinase inhibitor (TKI) therapy (January 1, 2011, through June 30, 2018). Patient characteristics and treatment patterns were characterized. Real‐world progression‐free survival (rwPFS) and time to discontinuation were calculated using the Kaplan‐Meier method. Results First‐line ALK TKI therapy was administered to 581 patients (27.5% had brain metastasis on or prior to initiation) and second‐line ALK TKI therapy to 254 patients post crizotinib (45.7% had brain metastasis on or prior to second‐line ALK TKI initiation). Crizotinib (84.6%; n = 492) was the most commonly administered first‐line ALK TKI therapy. For second‐line ALK TKI post crizotinib (n = 254), 49.6% received ceritinib, 41.7% received alectinib, 5.9% received crizotinib retreatment, and 2.8% received brigatinib. Median (95% confidence interval [CI]) rwPFS was 7.47 (6.48–8.32) months for first‐line and 7.30 (5.72–8.42) months for second‐line ALK TKI. Median (95% CI) rwPFS was significantly longer among first‐line ALK TKI patients without than with brain metastasis (8.52 [7.57–10.59] vs. 4.97 [3.75–5.99] months; p < .0001) and patients with brain metastasis on or prior to first‐line ALK TKI therapy had a significantly increased risk of progression (hazard ratio ± SE, 1.976 ± 0.112; p < .0001). Conclusion Median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for first‐ and second‐line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population. Implications for Practice Results presented herein describe real‐world treatment of advanced ALK+ NSCLC with ALK TKI therapies from January 2011 through June 2018. Crizotinib was the most commonly prescribed first‐line ALK TKI therapy in this patient population, but the majority of data analyzed were obtained prior to Food and Drug Administration approval of alectinib and ceritinib in the first‐line ALK TKI setting. Physicians should monitor patients closely to help identify when a change in treatment should occur. Patients with non‐small cell lung cancer (NSCLC) characterized by ALK rearrangements may benefit from ALK tyrosine kinase inhibitor (TKI) therapies. This article summarizes the characteristics of patients with ALK+ advanced NSCLC treated with ALK TKI therapy, describes treatment pathways and duration for these patients, and examines real‐world progression‐free survival and treatment discontinuation for patients receiving first‐line and second‐line ALK TKI therapy overall and for the subgroups of patients with and without pre‐existing brain metastasis at ALK TKI initiation

Test structures for the characterization of MEMS and CMOS integration technology

Test structures have been used to study the feasibility of bonding MEMS to CMOS wafers to create an integrated system. This involves bonding of prefabricated wafers and creating interconnects between the bonded wafers. Bonding of prefabricated wafers has been demonstrated using a chemical-mechanical polishing enabled surface planarization process and an oxygen plasma assisted low temperature wafer bonding process. Two interwafer connection approaches have been evaluated. For an oxide bonding approach, interconnects between wafers are established through contact vias, using a standard multilevel metallization process after the wafer bonding process. Resistances of 3.8-5.2 Ω have been obtained from via chain test structures and an average specific contact resistivity of 1.7 × 10-8 Ωcm2, measured from the single via Kelvin structures. For a direct metal contact approach, electrical connections have been achieved during the bonding anneal stage due to stress relief of the aluminium film.</p

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

Abstract 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. Initially, symptomatic AEs were selected based on literature and product labeling reviews, and then core sets of symptomatic AEs were identified by patient and clinician interviews. Qualitative and descriptive analyses were performed using the data collected from three iterative rounds of patient interviews. Results During concept elicitation interviews involving 29 patients, 12 symptomatic AEs were identified and were then adapted into a 25‐item PRO‐CTCAE form for use in future clinical trials along with commonly used PRO measures. Cognitive interviews showed that the PRO‐CTCAE items were easy to answer and appropriate for assessing the patients' experience with symptomatic AEs. This study also assessed disease symptoms, impacts, and overall patient experience. Conclusions The 25‐item PRO‐CTCAE form captures the most relevant symptomatic AEs in this patient population, and it is available for future studies. Baseline characterization of AEs associated with this distinct patient group contributes to our broader knowledge about NSCLC and through platforms like Project Patient Voice will expand our understanding of treatment tolerability and safety for NSCLC. Ultimately, this data collection will help inform decision‐making for patients, caregivers, healthcare providers, and regulators

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

Introduction: This study describes treatment patterns and outcomes in patients with NSCLC with EGFR exon 20 insertions (EGFRex20ins) in the United States. Methods: The Flatiron Health electronic health record database was used to select three cohorts among patients diagnosed with NSCLC with EGFRex20ins (January 1, 2011–February 29, 2020): (1) first-line (1L) or patients receiving 1L therapy after documented EGFRex20ins; (2) second or later-line (≥2L) or patients receiving ≥2L therapy after documented EGFRex20ins; 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 EGFRex20ins 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. Results: Of 237 patients with EGFRex20ins-mutated NSCLC, 129 and 114 patients were included in the 1L and ≥2L cohorts, respectively. In 1L patients, platinum chemotherapy plus nonplatinum chemotherapy (31.0%) and EGFR tyrosine kinase inhibitors (28.7%) were the most common regimens. In ≥2L patients, immuno-oncology monotherapy (28.1%) and EGFR tyrosine kinase inhibitors (17.5%) were the most common index treatments. For any 1L, ≥2L, and ≥2L postplatinum trial-aligned patients, the confirmed overall response rate was 18.6%, 9.6%, and 14.0%, respectively; the median overall survival was 17.0, 13.6, and 11.5 months; the median progression-free survival was 5.2, 3.7, and 3.3 months, respectively. Conclusions: The outcomes for patients with NSCLC with EGFRex20ins were poor. This real-world study provides a benchmark on treatment outcomes in this patient population and highlights the unmet need for improved therapeutic options