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Background/Objectives: This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. Methods: In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017-31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan-Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. Results: Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank p < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both p < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. Conclusions: Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups.
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BACKGROUND: Clinical practice guidelines recommend broad-panel genomic profiling to identify actionable genomic alterations for patients with advanced non-small cell lung cancer (aNSCLC). OBJECTIVE: To assess the cost-effectiveness of large-panel next-generation sequencing (LP-NGS) compared with current empirical single-gene test (SGT) patterns to inform first-line treatment decisions for patients with aNSCLC from a US commercial payer perspective, accounting for the effect of testing turnaround time and time to treatment initiation. METHODS: We developed a discrete-event simulation model to estimate the impact of LP-NGS vs SGT for patients with nonsquamous aNSCLC. Discrete events and timing included testing patterns, receipt of the initial test result, treatment initiation (targeted vs nontargeted therapies), switching, retesting, rebiopsies, clinical trial participation, progression on therapy, and death. LP-NGS and SGT cohorts each comprised 100,000 adults with aNSCLC simulated over a 5-year postdiagnosis period, assumed to have the same distribution of genomic alterations. The model predicted the proportion of patients receiving appropriate first-line therapy according to clinical practice guidelines. Economic outcomes included expected life-years gained, quality-adjusted life-years, and the total costs of care over 5 years. Sensitivity and scenario analyses explored the robustness of the base-case model results. RESULTS: In the base-case model, LP-NGS was likely to identify more alterations than SGT. Total 5-year costs per patient were $539,658 for LP-NGS and $544,550 for SGT (net difference, $4,892 lower costs per patient for LP-NGS), which is likely to be cost-effective 95.1% of the time. The most influential model parameters on the 5-year total costs of care were preprogression nondrug medical costs on nontargeted therapy, NGS turnaround time, and clinical trial participation. CONCLUSIONS: This study suggests that LP-NGS to guide first-line treatment decisions is clinically more appropriate (more likely to identify alterations and subsequently allocate patients to clinically appropriate therapy) and provides a dominant cost-effectiveness treatment strategy over 5 years for patients with newly diagnosed aNSCLC in the United States.
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Carcinoma de Pulmón de Células no Pequeñas , Análisis Costo-Beneficio , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/economía , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/economía , Secuenciación de Nucleótidos de Alto Rendimiento/economía , Años de Vida Ajustados por Calidad de Vida , Masculino , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. MATERIALS AND METHODS: This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients agedâ ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. RESULTS: A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. CONCLUSION: Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Molecular Dirigida , Oncogenes , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Estudios Retrospectivos , Terapia Molecular Dirigida/métodos , Anciano , Adulto , Biomarcadores de Tumor/genética , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Randomized trials have demonstrated that anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) can be safe and efficacious treatments for patients with ALK-positive advanced non-small-cell lung cancer (aNSCLC). However, their safety, tolerability, effectiveness, and patterns of use in real-world patients remain understudied. OBJECTIVE: We sought to assess the overall treatment pattern characteristics, safety, and effectiveness outcomes of real-world patients with ALK-positive aNSCLC receiving ALK TKIs. PATIENTS AND METHODS: This retrospective cohort study using electronic health record data included adult patients with ALK-positive aNSCLC receiving ALK TKIs between January 2012 and November 2021 at a large tertiary medical center, University of California, San Francisco (UCSF), with alectinib or crizotinib as the initial ALK TKI therapy. Our primary endpoints included the incidence of treatment changes (treatment dose adjustments, interruptions, and discontinuations) during the initial ALK TKI treatment, the count and type of subsequent treatments, rates of serious adverse events (sAEs), and major adverse events (mAEs) leading to any ALK TKI treatment changes. Secondary endpoints included the hazard ratios (HRs) for median mAE-free survival (mAEFS), real-world progression-free survival (rwPFS), and overall survival (OS) when comparing alectinib with crizotinib. RESULTS: The cohort consisted of 117 adult patients (70 alectinib and 47 crizotinib) with ALK-positive aNSCLC, with 24.8%, 17.9%, and 6.0% experiencing treatment dose adjustments, interruptions, and discontinuation, respectively. Of the 73 patients whose ALK TKI treatments were discontinued, 68 received subsequent treatments including newer generations of ALK TKIs, immune checkpoint inhibitors, and chemotherapies. The most common mAEs were rash (9.9%) and bradycardia (7.0%) for alectinib and liver toxicity (19.1%) for crizotinib. The most common sAEs were pericardial effusion (5.6%) and pleural effusion (5.6%) for alectinib and pulmonary embolism (6.4%) for crizotinib. Patients receiving alectinib versus crizotinib as their first ALK TKI treatment experienced significantly prolonged median rwPFS (29.3 versus 10.4 months) with an HR of 0.38 (95% CI 0.21-0.67), while prolonged median mAEFS (not reached versus 91.3 months) and OS (54.1 versus 45.8 months) were observed in patients receiving alectinib versus crizotinib but did not reach statistical significance. Yet, it is worth noting that there was a high degree of cross-over post-progression, which could significantly confound the overall survival measures. CONCLUSIONS: We found that ALK TKIs were highly tolerable, and alectinib was associated with favorable survival outcomes with longer time to adverse events (AE) requiring medical interventions, disease progression, and death, in the context of real-world use. Proactive monitoring for adverse events such as rash, bradycardia, and hepatotoxicity may help further promote the safe and optimal use of ALK TKIs in the treatment of patients with aNSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Crizotinib/farmacología , Crizotinib/uso terapéutico , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Bradicardia/inducido químicamente , Bradicardia/tratamiento farmacológico , Quinasa de Linfoma Anaplásico/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina QuinasasRESUMEN
Introduction: Patients with early NSCLC (eNSCLC) who experience recurrence are associated with worse survival outcomes, but the economic burden of recurrence is not well characterized. This study evaluated the incremental health care resource utilization and costs of recurrence in Medicare patients with resected eNSCLC. Methods: This retrospective observational study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims. Eligible patients were 65 years and older with newly diagnosed NSCLC stages IB to IIIA (American Joint Committee on Cancer Staging Manual, seventh edition) and surgery between January 2010 and December 2017. Continuous enrollment criteria were applied to ensure appropriate data capture. Per patient per month (PPPM) health care resource utilization and all-cause direct costs were compared for patients with versus without recurrence, which was identified from claims data using diagnosis, procedure, or drug codes. Patients were matched (1:1) using exact matching on cancer stage and treatment, and propensity score matching on other characteristics. Results: In total, 2035 (44%) out of 4595 patients had evidence of recurrence. After matching, 1494 patients were included in each cohort. Patients with recurrence had a significantly higher number of inpatient visits (+0.25 PPPM), outpatient visits (+1.10 PPPM), physician services (+3.70 PPPM), and emergency department (ED) visits (+0.25 PPPM; all p < 0.001). The average follow-up PPPM cost in the recurrence cohort was U.S. dollars $7437 and $1118 in the no-recurrence cohort, resulting in a difference of $6319 PPPM (p < 0.001) with inpatient costs as the largest contributor. Conclusions: On the basis of a real-world population, the recurrence among patients with resected eNSCLC is associated with increased health care resource utilization and costs.
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Aim: Atezolizumab improved disease-free survival (DFS) versus best supportive care (BSC) as adjuvant treatment following resection and platinum-based chemotherapy for stage II-IIIA PD-L1+ NSCLC in IMpower010. Materials & methods: This cost-effectiveness study evaluated atezolizumab versus BSC (US commercial payer perspective) using a Markov model with DFS, locoregional recurrence, first- and second-line metastatic recurrence and death health states, and a lifetime time horizon with 3% annual discounting. Results: Atezolizumab provided 1.045 additional quality-adjusted life-years (QALY) at an incremental cost of $48,956, yielding an incremental cost-effectiveness ratio of $46,859/QALY. Scenario analysis showed similar findings in a Medicare population ($48,512/QALY). Conclusion: At a willingness-to-pay threshold of $150,000/QALY and an incremental cost-effectiveness ratio of $46,859/QALY, atezolizumab is cost-effective versus BSC for adjuvant NSCLC treatment.
Atezolizumab treatment is 'cost-effective' for people in the USA with stage IIIIIA PD-L1+ non-small-cell lung cancer after surgery and chemotherapy. Until recently, people whose doctors told them they have stage IIIIIA non-small-cell lung cancer with PD-L1 expression on ≥1% of tumor cells (known as 'PD-L1+') did not have many treatment options beyond chemotherapy after surgery. Their cancer often returns even after chemotherapy. One treatment called atezolizumab showed good survival results in clinical trials and is approved in the USA for treatment after the lung tumor has been removed in surgery. Understanding how better survival and quality of life is related to the costs of treatment (known as 'costeffectiveness') is important. For example, insurance companies in the USA may use this information to decide what cancer drugs are preferred for insurance coverage. This study found that atezolizumab treatment was 'cost-effective' for people in the USA with stage IIIIIA PD-L1+ non-small-cell lung cancer when it was given after surgery and chemotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Neoplasias Pulmonares/tratamiento farmacológico , Análisis Costo-Beneficio , Antígeno B7-H1 , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Background: This study investigated real-world treatment patterns and overall survival (OS) in early non-small-cell lung cancer patients and the association between OS and time-to-adjuvant-treatment. Materials & methods: This retrospective study using Surveillance, Epidemiology and End Results data linked with Medicare claims included resected early non-small-cell lung cancer patients between 2010 and 2015. Unadjusted OS analyses used Kaplan-Meier curves; adjusted OS analyses used extended Cox proportional hazards models. Results: Only 54-71% of stage II-IIIA patients received any adjuvant treatment. Adjusted risk of death was higher when starting treatment outside 6-8 weeks after surgery (p < 0.05). Conclusion: Improved systemic therapy in the adjuvant chemotherapy setting is needed.
Lung cancer is one of the deadliest cancers in the USA. Most lung cancers are a type called non-small-cell lung cancer (NSCLC). Patients with NSCLC that has not spread to other parts of the body generally have surgery and may receive treatment before surgery, after surgery or both to help fight the cancer. It is not clear how often people receive treatment before or after surgery. It is important to know how patients are being treated because it helps clinicians decide how to use the new treatments that are becoming available. This study used a large database of more than 7000 people aged 65 years and older with lung cancer in the USA to understand how they are treated. More than a third of patients had stage IA NSCLC (39%), followed by stage IB (24%), stage II (20%), stage IIIA (15%) and stage IIIB (2%). Most people had surgery (64%) and some received another treatment after surgery (27%). That treatment was most often about 2 months of chemotherapy, on average. The study also tried to understand how the timing of treatment may have been important for their survival. People who received treatment after surgery lived the longest if they received that treatment about 68 weeks after the surgery. Overall, the study showed that a substantial proportion of people do not receive treatment for their NSCLC after surgery, even though treatment after surgery is recommended by medical guidelines. There is a need for more effective treatments for these patients, and when those treatments are given may be important for their survival.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anciano , Estados Unidos/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Medicare , Quimioterapia Adyuvante , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Recurrence of early-stage non-small cell lung cancer (eNSCLC) is associated with significant mortality and costs. Atezolizumab (ATZ) was recently approved as adjuvant treatment following resection and platinum-based chemotherapy for adults with stage II-IIIA NSCLC with PD-L1 expression ≥1% after demonstrating significant improvement in disease-free survival (DFS) relative to best supportive care (BSC) in the IMpower010 trial (NCT02486718). This study evaluated the population-level impact of ATZ as adjuvant treatment for eNSCLC in the United States by estimating the number and costs of recurrences avoided. METHODS: A Monte Carlo simulation model estimated the cumulative number of recurrences and deaths prevented, along with direct, indirect, and terminal care costs, by treating eNSCLC patients with ATZ compared to BSC. The model included eligible patients treated in any given year and followed over a 5-year period. Recurrence and mortality rates and costs were based on the IMpower010 data and supplemented by estimates from published literature. RESULTS: An estimated 4400 eNSCLC patients in the United States were eligible for adjuvant ATZ in any given year, of whom 2387 would experience recurrence within 5 years with BSC. Following the introduction of ATZ, 1030 (95% confidence interval [CI]: 1023, 1036) recurrences and 369 (95% CI: 362, 376) deaths would be avoided with estimated reductions in cumulative recurrence-related direct, indirect, and terminal care costs of $785 million, $15 million, and $32 million, respectively, over a 5-year time horizon. CONCLUSIONS: Adjuvant ATZ is estimated to prevent a significant number of recurrences and reduce the economic burden of eNSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Estados Unidos/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Análisis Costo-BeneficioRESUMEN
BACKGROUND: Evidence suggests that patients with Medicaid experience lower-quality cancer care than those with commercial insurance. Whether this trend persists in the era of personalized medicine is unclear. This study examined the associations between Medicaid (vs commercial) insurance and receipt of biomarker testing, targeted therapy, and overall survival in patients with advanced non-small cell lung cancer (aNSCLC). METHODS: We conducted a retrospective study of patients who received an aNSCLC diagnosis from January 2011 to September 2019 using a nationwide US healthcare database. Eligible patients were aged 18 to 64 years with Medicaid or commercial insurance at diagnosis. Receipt of biomarker testing (ALK, EGFR, ROS1, BRAF, and PD-L1) was assessed. The likelihood of testing, biomarker-driven therapy (cancer immunotherapy or tyrosine kinase inhibitor treatment), and mortality were compared by insurance type using adjusted Cox regression. RESULTS: Our sample included 6,145 commercially insured and 865 Medicaid beneficiaries. Medicaid beneficiaries were more likely to be Black or African American (20% vs 9.3%; P <.001) and were less likely to have undergone biomarker testing (57% vs 71%; P <.001). In the adjusted analysis, Medicaid beneficiaries were less likely to have evidence of testing (hazard ratio [HR], 0.81; P <.001), any first-line treatment (HR, 0.72; P <.001), and first-line biomarker-driven therapy (HR, 0.70; P <.001). Medicaid beneficiaries with evidence of biomarker testing had a lower risk of death compared with those without evidence of biomarker testing (HR, 1.27 [95% CI, 1.06-1.52]; P =.010). Higher risk of death was observed in patients with Medicaid versus commercially insured patients (HR, 1.23; P <.001); this result remained unchanged after adjusting for biomarker testing (HR, 1.22; P < .001) but was partially ameliorated after adjustment for testing and treatment type (HR, 1.12; P =.010). CONCLUSIONS: Medicaid beneficiaries with aNSCLC were less likely to receive biomarker testing and biomarker-driven therapies, which may in part contribute to a higher observed risk of mortality compared with commercially insured patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Humanos , Cobertura del Seguro , Seguro de Salud , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Medicaid , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: This study investigated biomarker testing and biomarker-guided treatment among patients with metastatic NSCLC in a real-world setting. METHODS: This retrospective study examined adult patients diagnosed with de novo mNSCLC between 01-Jan-2016 and 30-Sep-2019, with follow-up through 31-Dec-2019 using The US Oncology Network structured electronic health records data, with chart review for a subset. RESULTS: Of 2257 patients, 76.3% had results for ≥1 driver mutation (DM) or programmed death ligand-1 (PD-L1) during the study observation period. The proportion with results for all 4 DM before 1L initiation increased from 2017 to 2019. Over 40% had results for anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and c-ros oncogene 1 (ROS1) and 22% for B-Raf proto-oncogene (BRAF) before 1L initiation by structured data. In the chart review subset (n = 197), >70% had results for ALK, EGFR, or ROS1 with 44% for BRAF. Of the 42 ALK+ patients, 5 had results before 1L treatment and 3 received 1L ALK inhibitors. Similar, for the other biomarkers, not all who tested positive for a DM received 1L targeted therapy. The proportion of biomarker-positive patients receiving 1L targeted therapy was higher in chart review versus structured data. However, in both analyses, a substantial proportion did not have results for all 4 DM plus PD-L1 tests for appropriate biomarker-directed 1L treatment selection. CONCLUSIONS: Despite increasing biomarker testing rates, reduced turnaround times, and availability of promising biomarker-based therapies, inadequate testing in the community oncology setting means that not all eligible patients are receiving the most effective therapies up front.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Antígeno B7-H1/metabolismo , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Estudios RetrospectivosRESUMEN
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in the United States. Several anaplastic lymphoma kinase (ALK) rearrangement inhibitors have been approved for the treatment of metastatic ALK-positive non-small cell lung cancer (NSCLC). Effective disease management requires an understanding of how these treatments are used in clinical practice, since low treatment adherence and/or early discontinuation have been associated with poor patient outcomes. Owing to the recency of approvals, real-world data on the use of ALK inhibitors in patients with ALKpositive NSCLC are currently limited; this represents a notable gap in our understanding of ALK treatment use. OBJECTIVE: To assess real-world adherence and persistence with ALK inhibitors in patients with ALK-positive NSCLC. METHODS: This retrospective observational study used US commercial claims for patients aged at least 18 years with lung cancer receiving ALK inhibitors (alectinib, brigatinib, ceritinib, crizotinib) between July 1, 2015, and December 31, 2018. Patients' first and any subsequent ALK inhibitor uses were categorized into ALK inhibitor-naive and ALK inhibitor-pretreated cohorts, respectively. Adherence was measured by medication possession ratio and persistence by time from treatment initiation to discontinuation (earliest of a treatment switch or greater than a 60-day gap). Descriptive statistics were used to summarize patient characteristics. Cohort comparisons were made using chi-square tests and t-tests. Persistence and time to next ALK inhibitor were analyzed using Kaplan-Meier methods and the log-rank test. Poisson and Cox regression models of adherence and persistence, respectively, were applied to compare ALK inhibitors. RESULTS: We identified 1,482 patients treated with alectinib (n = 445) or crizotinib (n = 1,037) in the ALK inhibitor-naive cohort; 604, 142, and 134 patients received alectinib, brigatinib, or ceritinib in the ALK inhibitor-pretreated cohort. Adherence during the treatment period (95%-97%) and the proportion of patients with a medication possession ratio of at least 0.8 (92%-95%) were similar for all ALK inhibitors. In the ALK inhibitor-naive cohort, median time to treatment discontinuation with alectinib and crizotinib was 27.1 and 8.8 months, respectively; patients receiving alectinib were 46% less likely to discontinue than patients receiving crizotinib (adjusted hazard ratio [aHR] [95% CI]: 0.54 [0.44-0.65]; P < 0.0001). In the ALK inhibitor-pretreated cohort, the discontinuation risk for alectinib was 64% lower than for ceritinib (aHR [95% CI]: 0.36 [0.27-0.49]; P < 0.0001) and 34% lower than for brigatinib (aHR [95% CI]: 0.66 [0.42-1.02]; P = 0.062). CONCLUSIONS: To our knowledge, this study is the first to address a current research gap by assessing real-world adherence and persistence with ALK inhibitors among patients with ALK-positive NSCLC in real-world clinical practice. Alectinib was associated with longer real-world persistence than other ALK inhibitors, despite similar adherence. Further research with more patients and longer follow-up is needed to link persistence to real-world clinical outcomes. DISCLOSURES: This study was funded by Genentech Inc. Ganti has received research support from Takeda and has provided consulting services to Genentech Inc., AstraZeneca, Flagship Biosciences, Cardinal Health, BioGene, Mirati Therapeutics, Blueprint Medicines, and G1 Therapeutics. Lin, Wong, and Ogale are employees of Genentech Inc. and may own stock in F. Hoffmann-La Roche. Yang was employed by Genentech Inc. at the time of this study. Part of the study findings were presented as a poster at the NCCN 2020 Virtual Annual Conference, April 9, 2020.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Cumplimiento de la Medicación , Adolescente , Adulto , Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Crizotinib/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Cumplimiento de la Medicación/estadística & datos numéricos , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
PURPOSE: In 2018, Medicare issued a national coverage determination (NCD) providing reimbursement for next-generation sequencing (NGS) tests for beneficiaries with advanced or metastatic cancer and no previous NGS testing. We examined the association between NCD implementation and NGS utilization trends in Medicare beneficiaries versus commercially insured patients. METHODS: This was a retrospective study of patients with advanced non-small-cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), or advanced melanoma with a de novo or recurrent advanced diagnosis from January 1, 2011, through December 30, 2019, using a nationwide US electronic health record-derived deidentified database. Patients were classified by insurance and by advanced diagnosis date. NGS testing was assessed by receipt of first NGS test result ≤ 60 days of advanced diagnosis. Interrupted time series analysis assessed NGS utilization pre- and post-NCD effective date by insurance type. RESULTS: The utilization and repeat NGS testing analysis included 70,290 and 4,295 patients, respectively. Use of NGS rose from < 1% in 2011 to > 45% in Q4 2019 in aNSCLC while remaining < 20% in mBC and advanced melanoma. Among patients with aNSCLC, mCRC, or mBC, NGS testing increased post-NCD versus pre-NCD (P < .05). There was no significant difference in trends pre- and post-NCD between Medicare beneficiaries and commercially insured patients in any tumor. Repeat NGS testing was similar before the NCD (Medicare v commercial: 24.8% v 28.5%). Post-NCD, fewer Medicare beneficiaries had repeat NGS testing (27.7% v 36.0%; P < .01). CONCLUSION: Trends in NGS utilization significantly changed post-NCD, although the magnitude of change was not significantly different by insurance type, indicating private insurers may also be incorporating NCD guidance. Implementation of the NCD may have limited use of repeat NGS testing in Medicare beneficiaries.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cobertura del Seguro , Medicare , Estudios Retrospectivos , Estados UnidosRESUMEN
DISCLOSURES: The writing of this letter was sponsored by Roche/Genentech. All authors are employees of, and hold stocks in, F. Hoffmann-La Roche Ltd/Genentech Inc.
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Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Benzamidas , Humanos , Indazoles , Pirazoles , PirimidinasRESUMEN
OBJECTIVE: To characterize Bacillus Calmette-Guérin (BCG) treatment patterns and associated outcomes in a large cohort of patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Our retrospective analysis of patients aged ≥66 years with stage 0-1 urothelial bladder carcinoma diagnosed between 2000 and 2012 in the United States Surveillance, Epidemiology, and End Results-Medicare database estimated proxies for recurrence and secondary events and both all-cause and bladder cancer-specific mortality. Proportional hazards models were used in conditional landmark analyses to compare adequate (≥5 induction instillations and ≥2 maintenance instillations) and inadequate BCG, stratified by National Comprehensive Cancer Network risk group. RESULTS: Of 39,532 patients who met the selection criteria, 16,225 (41.0%) received BCG; of them, 4602 (28.4%; 11.6% overall) received adequate treatment. Adequately treated patients were slightly younger and healthier than inadequately treated patients. Half of patients with intermediate- and high-risk NMIBC did not receive BCG; few received adequate treatment. At the 12-month landmark, adequate BCG treatment was associated with decreased risks of recurrence and of cancer-specific and all-cause mortality in patients with intermediate- and high-risk disease. CONCLUSION: We observed lower than expected use of adequate BCG treatment in patients with intermediate- to high-risk NMIBC despite evidence of improved outcomes, which suggested that practice patterns may not be in line with management recommendations in this population.
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Vacuna BCG/administración & dosificación , Carcinoma de Células Transicionales/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Intravesical , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Esquema de Medicación , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/prevención & control , Pautas de la Práctica en Medicina/tendencias , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVES: The goal of this study was to establish a claims-based mechanism for identifying patients with metastatic non-small cell lung cancer (mNSCLC) and high levels of patient-reported cancer-related symptoms who could benefit from engagement with health care programs. STUDY DESIGN: A cross-sectional survey of patients with mNSCLC was conducted from July 2017 to May 2018. Surveys were mailed to patients who were within 3 months of cancer treatment and enrolled in a Medicare Advantage health plan. METHODS: Pain, fatigue, and sleep disturbance were measured using the Patient-Reported Outcomes Measurement Information System. Depression was assessed using the Patient Health Questionnaire-2. Medical claims were linked to survey results to identify comorbidities and assess preindex health care resource utilization. Cluster analysis was used to differentiate patients based on patient-reported pain interference, pain intensity, depression, and sleep disturbance. Logistic regression was used to identify claims-based measures associated with more severe symptoms. RESULTS: For 698 respondents, 2 distinct symptom clusters were identified: a less severe (38.4%) cluster and a more severe (61.6%) cluster. Patients in the more severe cluster were younger, were more frequently dually eligible for Medicare and Medicaid, and more frequently had prescription fills for opioids. Claims-based factors associated with the more severe cluster included 2 or more 30-day fills for opioids in the prior 6 months, age younger than 75 years, depression diagnosis or antidepressants, bone metastases, and pain-related outpatient visits. CONCLUSIONS: The claims-based factors associated with the severe symptom cluster can enable identification of patients with mNSCLC who could benefit from clinical outreach programs to enhance the care and support provided to these patients.
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Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Revisión de Utilización de Seguros/estadística & datos numéricos , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/terapia , Aceptación de la Atención de Salud/estadística & datos numéricos , Brote de los Síntomas , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Medicare Part C/estadística & datos numéricos , Persona de Mediana Edad , Metástasis de la Neoplasia/fisiopatología , Metástasis de la Neoplasia/terapia , Estudios Retrospectivos , Estados UnidosRESUMEN
Aims: To describe healthcare utilization and cost associated with the short-term and long-term complications of cystectomy among commercially insured bladder cancer patients in the United States.Materials and methods: This retrospective, observational cohort study evaluated adults with bladder cancer receiving a transurethral resection of bladder tumor followed by a partial or radical cystectomy procedure using U.S. administrative claims from the 2005-2015 IBM MarketScan Commercial and Medicare Supplemental databases. Bladder cancer patients were classified into two cohorts: partial cystectomy or radical cystectomy. Cystectomy complications were identified during the cystectomy admission, short-term period, and long-term period. Complication-related utilization and cost outcomes were reported in aggregate during the cystectomy admission and per patient per month (PPPM) during the short-term and long-term follow-up periods.Results: Of 5136 patients who received a cystectomy, 488 (9.5%) received partial cystectomy and 4648 (90.5%) received radical cystectomy. The mean (SD) costs of complications during the cystectomy admission were $11,728 ($43,380) for radical cystectomy and $4657 ($25,668) for partial cystectomy. In the short-term period, PPPM complication-related healthcare costs were $638 [$3793] for partial cystectomy and $2681 [$14,705] for radical cystectomy. In the long-term period, PPPM complication-related healthcare costs were $544 [$2580] for partial cystectomy and $1619 [$7874] for radical cystectomy.Conclusions: Cystectomy-related complications, especially with radical cystectomy, present a substantial financial burden to patients and payers immediately after surgery as well as in the long term. Targeted interventions which improve clinical outcomes but reduce substantial costs associated with cystectomy for bladder cancer are needed.
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Cistectomía/efectos adversos , Costos de la Atención en Salud , Complicaciones Posoperatorias/economía , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Estudios RetrospectivosRESUMEN
BACKGROUND: Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC. METHODS: US administrative claims data (Truven Health MarketScan Commercial Databases) were used to assess trends in 1 L treatment initiation in mRCC (2006-2015) and characterize patterns of individual 1 L treatments, baseline characteristics, comorbidities and treatment-related AEs from 2011 through 2015. Outcomes were evaluated by drug class and route of administration. RESULTS: Ten-year trend analysis (n = 4270) showed that TK/VEGF-directed therapy rapidly became more common than mTOR-directed therapy, and oral treatments were favored over intravenous (IV) treatments. Overall, 1992 eligible patients initiated 1 L treatment for mRCC from 2011 through 2015: 1752 (88%) received TK/VEGF-directed agents and 233 (12%) received mTOR-directed agents; 1674 (84%) received oral treatments, and 318 (16%) received IV treatments. The most common 1 L treatment was sunitinib (n = 849), followed by pazopanib (n = 631), temsirolimus (n = 157) and bevacizumab (n = 154). Patient characteristics and comorbidities, including age, diabetes and congestive heart failure, were independent predictors of 1 L mRCC treatment choice. The three most common potentially 1 L treatment-related AEs were nausea/vomiting (128.2 per 100 patient-years [PY]), hypertension (69 per 100 PY) and renal insufficiency (44.6 per 100 PY). A wide variety of agents were used as second-line (2 L) therapy. Substantial latency of onset was observed for several potentially treatment-related toxicities in patients treated with TK/VEGF- or mTOR-directed agents. CONCLUSIONS: In the US, 1 L TK/VEGF inhibitor uptake in recent years appears largely in line with national approvals and guidelines, with varied 2 L agent use. Although retrospective evaluation of claims data cannot assess underlying causality, insights from these real-world RCC treatment and AE patterns will be useful in informing medical and payer decisions.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Renales/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Neoplasias Renales/epidemiología , Pautas de la Práctica en Medicina , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Estudios Transversales , Bases de Datos Factuales , Femenino , Encuestas de Atención de la Salud , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: To reduce health care costs and improve care, payers and physician groups are piloting value-based and episodic or bundled-care payment models in oncology. Disease progression and associated costs may affect these models, particularly if such programs do not account for disease severity and progression risk across patient populations. This study estimated the incremental cost of disease progression in patients diagnosed with metastatic breast cancer (mBC), colorectal cancer (mCRC) and lung cancer (mLC) and compared costs among patients with and without progression. METHODS: This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of mBC, mCRC, and mLC and systemic antineoplastic agent use from July 1, 2006, to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS: Of 5,709 patients with mBC, 3,707 patients with mCRC, and 5,201 patients with mLC, 56.8% of patients with mBC, 58.1% of those with mCRC, and 80.3% of those with mLC patients had evidence of disease progression over 12 months. Among patients with mBC and mCRC, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, which accounted for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with mBC, mCRC, and mLC. In each of the three cancer types, delays in progression were associated with lower health care costs. CONCLUSION: Progression of mLC, mBC, and mCRC was associated with higher health care costs over a 12-month period. Delayed cancer progression was associated with substantial cost reductions in patients with each of the three cancer types. IMPLICATIONS FOR PRACTICE: Data on the rates and incremental health care costs of disease progression in patients with solid tumor cancers are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with lung cancer, breast cancer, and colorectal cancer and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in our study quantify the economic value of delaying or preventing disease progression and may inform payers and physician groups about value-based payment programs.
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Neoplasias de la Mama/economía , Neoplasias Colorrectales/economía , Neoplasias Pulmonares/economía , Modelos Económicos , Anciano , Antineoplásicos/economía , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/epidemiología , Progresión de la Enfermedad , Costos de los Medicamentos , Femenino , Costos de la Atención en Salud , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/epidemiología , Masculino , Medicare/economía , Persona de Mediana Edad , Metástasis de la Neoplasia , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: To reduce health care costs and improve care, payers and physician groups are switching to quality-based and episodic or bundled-care models. Disease progression and associated costs may affect these models, particularly if such programs do not account for differences in disease severity and progression risk within the cohort. This study estimated the incremental cost of disease progression in patients diagnosed with chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), and non-Hodgkin's lymphoma (NHL) and compared costs among patients with and without progression. METHODS: This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of CLL, AML, and NHL and systemic antineoplastic agent use from July 1, 2006 to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS: Of 1,056 patients with CLL, 514 patients with AML, and 7,601 patients with NHL, 31.1% of patients with CLL, 63.8% of those with AML, and 36.9% of those with NHL had evidence of disease progression. Among patients with CLL and NHL, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, accounting for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with CLL, AML, and NHL. In each of the three cancer types, the longer disease progression was delayed, the lower the health care costs. CONCLUSION: Progression of CLL, AML, and NHL was associated with higher health care costs over a 12-month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types. IMPLICATIONS FOR PRACTICE: Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non-Hodgkin's lymphoma and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in this study will assist future studies in quantifying the cost impact of decreased progression rates and will inform payers and physician groups about setting rates for episode and bundled payment programs.
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Costos de la Atención en Salud , Leucemia Linfocítica Crónica de Células B/economía , Leucemia Mieloide Aguda/economía , Linfoma no Hodgkin/economía , Anciano , Antineoplásicos/economía , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Costos de los Medicamentos , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Mieloide Aguda/epidemiología , Linfoma no Hodgkin/epidemiología , Masculino , Medicare , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Bevacizumab is a standard first-line (L1) treatment for metastatic colorectal cancer (mCRC) patients regardless of RAS status. This retrospective study examined treatment patterns and outcomes in a community oncology sample of KRAS mutant mCRC patients treated with chemotherapy (C) or C plus bevacizumab (CB) in L1. METHODS: This study used medical records from the Vector Oncology Data Warehouse. Eligible patients were confirmed KRAS mutant mCRC and received L1 C or CB. Kaplan-Meier analysis assessed L1 progression-free survival (PFS) and overall survival (OS). Cox regression models examined the interaction of tumor location (R/L) with treatment. RESULTS: CB (n = 264) compared to C (n = 109) patients were younger, less likely performance status (PS) impaired, and more likely with liver metastases. Median unadjusted PFS was 10.41 months (95% CI 9.0-11.3) in CB and 7.66 months (95% CI 6.5-9.1) in C patients (p = 0.174). Median unadjusted OS was 26.91 months (95% CI 24.3-29.3) in CB and 23.33 months (95% CI 19.7-29.2) in C patients (p = 0.571). For patients with right- vs. left-sided tumors, C (but not CB)-treated patients had higher adjusted risk for progression (HR = 1.715, 95% CI 1.108, 2.653; p = 0.015). CONCLUSIONS: CB- vs. C-treated KRAS mutant mCRC patients may have a meaningful PFS benefit. Patients with right-sided tumors treated with C were at higher risk for disease progression than patients with left-sided tumors. Tumor location had no significant effect on outcomes in the CB cohort.