Real-World Neoadjuvant Treatment Patterns and Outcomes in Resected Non-Small-Cell Lung Cancer.

BACKGROUND: Novel neoadjuvant chemoimmunotherapy treatments are being investigated for locally advanced non-small-cell lung cancer (NSCLC), but real-world outcomes for neoadjuvant treatments are poorly understood. This study examined neoadjuvant treatment patterns, real-world event-free survival (rwEFS) and overall survival (OS) in patients with resected, stage II-III NSCLC in the United States (US). METHODS: This retrospective study identified patients in the SEER-Medicare database (2007-2019) with newly diagnosed stage II, IIIA, and IIIB (N2) NSCLC (AJCC 8th edition) treated with neoadjuvant chemo/chemoradiotherapy and resection (index date: neoadjuvant therapy initiation). Neoadjuvant treatment regimens were described. rwEFS (time from index to first recurrence or death, whichever occurred first) and OS (time from index to death) were summarized by Kaplan-Meier analysis for overall population, by disease stage at diagnosis, and by neoadjuvant treatment modality. RESULTS: 221 patients (stage II, N=70; stage III, N=151) met eligibility criteria. The median follow-up from index was 32.7 months. All patients received neoadjuvant chemotherapy (51%) or chemoradiotherapy (49%) prior to surgery; 97% of patients received platinum-based regimens, among which carboplatin+paclitaxel was the most frequent (45%). In all patients, median rwEFS was 17.6 months and 5-year rwEFS was 20.9%; median OS was 48.5 months and 5-year OS was 44.9%. 71% of patients had disease recurrence during follow-up; among them, 28% developed locoregional recurrence as the first recurrence event. CONCLUSIONS: Patients with resected, stage II-III NSCLC who received neoadjuvant chemo/chemoradiotherapy have high rates of disease recurrence and poor survival outcomes, highlighting need for more effective treatments to improve survival rates.

Event-free survival as a predictor of overall survival and recurrence burden of patients with non-small cell lung cancer receiving neoadjuvant therapy.

OBJECTIVES: Event-free survival has replaced overall survival as a primary end point in many recent and ongoing clinical trials. This study aims to examine the correlation between real-world event-free survival and overall survival and to assess the clinical and economic burden associated with disease recurrence among patients with resected stage II to III non-small cell lung cancer who received neoadjuvant therapy in the United States. METHODS: This retrospective study used the Surveillance, Epidemiology, and End Results Medicare database (2007-2019) to identify patients with newly diagnosed, resected, stage II to IIIB (N2) non-small cell lung cancer who received neoadjuvant therapy. The correlation between real-world event-free survival and overall survival was assessed using the normal scores rank correlation and landmark analysis. Overall survival, all-cause health care resource use and costs, and non-small cell lung cancer-related health care resource use and costs were compared between patients with and without recurrence. RESULTS: A total of 221 patients met the eligibility criteria (median follow-up time from neoadjuvant treatment initiation: 32.7 months). The mean age was 72.1 years, and 57.0% of patients were male. Real-world, event-free survival and overall survival are positively and significantly correlated (0.68; 95% CI, 0.52-0.79). Patients with recurrence had significantly shorter median overall survival (19.3 vs 116.9 months), 4.59 times increased risk of death (95% CI, 2.56-8.26), and significantly higher all-cause and non-small cell lung cancer-related health care resource use and costs (adjusted mean monthly costs per patient difference: $5758 and $3187, respectively [all P < .001]). CONCLUSIONS: These findings help validate event-free survival as a clinically meaningful end point and strong predictor for overall survival and highlight the need for additional novel therapies that may delay or prevent recurrence in resectable stage II and III non-small cell lung cancer.

Health Care Resource Utilization and Costs for Patients with Spinal Muscular Atrophy: Findings from a Retrospective US Claims Database Analysis.

INTRODUCTION: Spinal muscular atrophy (SMA) is a neurogenic disorder associated with progressive loss of muscle function, respiratory failure, and premature mortality. This study aimed to describe and compare real-world health care resource utilization (HCRU) and costs for US patients with SMA treated with disease-modifying treatments, including onasemnogene abeparvovec, nusinersen, and/or risdiplam. METHODS: This study used claims and structured electronic medical record data from the HealthVerity claims database (January 1, 2017-March 31, 2021). Eligible patients were aged ≤ 2 years at index (treatment initiation or switch), diagnosed with SMA, had ≥ 1 pharmacy/medical claim for onasemnogene abeparvovec, nusinersen, and/or risdiplam, and continuous enrollment ≥ 1 month pre- and ≥ 2 months post-index. SMA-related HCRU and costs during the study period (> 12 months post-index) were compared between treatment groups before and after propensity score weighting. Costs were adjusted to 2021 USD. RESULTS: Of 74 included patients, 62 (83.8%) received nusinersen and 12 (16.2%) received onasemnogene abeparvovec (monotherapy, n = 9; onasemnogene abeparvovec after nusinersen [switching], n = 3). After weighting, nusinersen-treated patients had greater annual numbers of inpatient (mean 5.3 nusinersen vs. 1.8 onasemnogene abeparvovec) and emergency department (mean 3.0 nusinersen vs. 1.5 onasemnogene abeparvovec; p < 0.05) visits, and greater annual SMA-related medical costs (mean $78,446 nusinersen vs. $29,438 onasemnogene abeparvovec; mean difference $49,007, p < 0.05) than onasemnogene abeparvovec-treated patients. Onasemnogene abeparvovec-treated patients incurred greater SMA-treatment pharmacy costs than nusinersen-treated patients (mean $2,241,875 onasemnogene abeparvovec vs. $693,191 nusinersen; mean difference $1,548,684, p < 0.05). CONCLUSIONS: SMA is associated with substantial economic burden. Patients treated with onasemnogene abeparvovec had greater SMA treatment-related pharmacy costs but lower SMA-related HCRU and medical costs compared with patients receiving nusinersen monotherapy.

Spinal muscular atrophy (SMA) is a crippling neurodegenerative disease with symptoms of respiratory failure, muscle weakness and loss of function, and premature death. This study describes and compares real-world health care resource utilization (HCRU) and costs for US patients with SMA receiving current treatments (e.g., onasemnogene abeparvovec, nusinersen, risdiplam) using claims and electronic medical record data from a US claims database. Patients included (n = 74) in the study were ≤ 2 years old at treatment initiation/switching of treatments (index), had been diagnosed with SMA and had one or more pharmacy or medical claim for onasemnogene abeparvovec, nusinersen, or risdiplam, and were continuously enrolled for ≥ 1 month before and ≥ 2 months after index. SMA-related HCRU and costs during the study period (up to 12 months post-index) were compared between treatment groups before and after propensity score weighting, with costs adjusted to 2021 USD. Propensity score weighting allows better comparison between patients in treatment and comparison groups by assigning patients different "weights." This weighting allows investigators to be certain that differences in outcomes between patient groups are a result of a particular treatment. After weighting, nusinersen-treated patients had a greater number of inpatient and emergency department visits and greater SMA-related medical costs annually, whereas patients who received onasemnogene abeparvovec had greater pharmacy costs. Our study indicates the greater medical costs among patients receiving nusinersen were largely driven by invasive procedures, such as tracheostomy and gastrostomy, that required hospitalization, but the exact mechanism of greater HCRU/costs associated with nusinersen needs to be further assessed.

Evaluation of disease-free survival as a predictor of overall survival and assessment of real-world burden of disease recurrence in resected early-stage non-small cell lung cancer.

BACKGROUND: Intermediate endpoints, such as disease-free survival (DFS), have shown good correlation with overall survival (OS) in early-stage non-small cell lung cancer (NSCLC) clinical trials. However, real-world data are limited, and no previous real-world study has quantified the clinical and economic burden of disease recurrence. OBJECTIVE: To examine the association between real-world DFS (rwDFS) and OS and quantify the association between NSCLC recurrence and health care resource utilization (HCRU), health care costs, and OS in patients with resected early-stage NSCLC in the United States. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2019) for patients with newly diagnosed stage IB (tumor size ≥ 4 cm) to IIIA (American Joint Committee on Cancer 7th edition) NSCLC who underwent surgery for primary NSCLC were analyzed in this retrospective observational study. Baseline patient demographic and clinical characteristics were described. rwDFS and OS were compared between patients with vs without recurrence using Kaplan-Meier curves and the log-rank test; their correlation was assessed using normal scores rank correlation. All-cause and NSCLC-related HCRU and health care costs were summarized, and mean monthly allcause and NSCLC-related health care costs were compared between cohorts using generalized linear models. RESULTS: Of the 1,761 patients who underwent surgery, 1,182 (67.1%) had disease recurrence; these patients had shorter OS from the index date and shorter subsequent OS at each postsurgery landmark (ie, 1, 3, and 5 years) than those without recurrence (all P < 0.001). OS and rwDFS were significantly correlated (0.57; P < 0.001). Patients with recurrence also had significantly higher all-cause and NSCLC-related HCRU and mean monthly all-cause and NSCLC-related health care costs during the study period. CONCLUSIONS: Postsurgery rwDFS was significantly correlated with OS in patients with early-stage NSCLC. Patients with postsurgery recurrence had a higher risk of death and incurred higher HCRU and health care costs than those without recurrence. These findings highlight the importance of preventing or delaying recurrence in patients with resected NSCLC. DISCLOSURES: Dr West is Senior Medical Director at AccessHope and an Associate Professor at City of Hope. He also serves on the advisory board for Amgen, AstraZeneca, Genentech/Roche, Gilead, Merck, Mirati Therapeutics, Regeneron, Summit Therapeutics, and Takeda and as a speaker for AstraZeneca and Merck. Drs Hu, Chirovsky, and Samkari are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and own stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Drs Zhang, Song, Gao, and Signorovitch, Mr Lerner, and Ms Jiang are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, which funded the development and conduct of this study and article. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention's National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the National Cancer Institute's SEER Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors.

Treatment Patterns and Outcomes in Resected Early-stage Non-small Cell Lung Cancer: An Analysis of the SEER-Medicare Data.

BACKGROUND: As the non-small cell lung cancer (NSCLC) adjuvant treatment landscape evolves, an evaluation of treatment patterns and outcomes of patients with early-stage, resected NSCLC eligible for adjuvant treatment in routine clinical practice is needed to better understand the unmet needs in this patient population. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2007-2019) were used to identify patients with newly diagnosed stage IB (tumor size ≥4cm)-IIIA (AJCC 7th edition) NSCLC who received primary surgery (index date). We assessed adjuvant treatment patterns, real-world disease-free survival (rwDFS; time from index date to first recurrence or death) and overall survival (OS; time from index date to death), and loco-regional recurrence pattern and treatment distribution. RESULTS: Among 1761 patients with primary surgery, mean age was 73.8 years; 47.9% were male; and 83.9% were white. Approximately 41% of patients received adjuvant chemotherapy; median time from surgery to adjuvant chemotherapy initiation was 48 days, and the most frequently observed adjuvant chemotherapy regimen was carboplatin+paclitaxel (24.5%). In the overall population, median rwDFS was 24.8 months and OS was 76.7 months; 5-year rwDFS and OS rates were 29.3% and 57.5%, respectively. Among 392 patients with loco-regional recurrence, the most frequently observed treatment was curative radiation monotherapy (28.2%). CONCLUSION: Despite clinical guideline recommendations, rate of adjuvant chemotherapy among patients with resected early-stage NSCLC was low in clinical practice. Overall, among patients with early-stage NSCLC treated with conventional primary surgery, poor survival outcomes were observed, highlighting the need for and importance of more effective adjuvant treatments.