Projecting long-term clinical outcomes with larotrectinib compared with immune checkpoint inhibitors in metastatic nonsmall cell lung cancer and differentiated thyroid cancer.

BACKGROUND: Larotrectinib is approved for patients with advanced NTRK gene fusion-positive solid tumors. Prior studies demonstrated promising results with larotrectinib compared with other systemic therapy. However, comparisons to checkpoint inhibitors, such as nivolumab or pembrolizumab, have not been done. OBJECTIVE: To estimate and compare expected life-years (LYs) and quality-adjusted LYs (QALYs) for patients with nonsmall cell lung cancer (NSCLC) eligible for larotrectinib vs patients with unknown NTRK gene fusion status on nivolumab or pembrolizumab. We also assessed patients with metastatic differentiated thyroid cancer (DTC), as pembrolizumab may be considered in certain circumstances. METHODS: We developed partitioned survival models to project long-term comparative effectiveness of larotrectinib vs nivolumab or pembrolizumab. Larotrectinib survival data were derived from an updated July 2021 analysis of 21 adult patients (≥18 years of age) with metastatic NTRK gene fusion-positive NSCLC and 21 with DTC. Survival inputs for nivolumab and pembrolizumab were obtained from published articles. Progression-free and overall survival were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Log-normal). Exponential fits were chosen based on goodness-of-fit and clinical plausibility. RESULTS: In NSCLC, larotrectinib resulted in gains of 5.87 and 5.91 LYs compared to nivolumab and pembrolizumab, respectively, which translated to gains of 3.53 and 3.56 QALYs. In DTC, larotrectinib resulted in a gain of 5.23 LYs and 4.24 QALYs compared to pembrolizumab. CONCLUSIONS: In metastatic NSCLC and DTC, larotrectinib may produce substantial life expectancy and QALY gains compared to immune checkpoint inhibitors. Additional data with longer follow-up will further inform this comparison.

Drug-drug interaction potential among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with novel androgen receptor inhibitors.

BACKGROUND: Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients are often older and use concurrent medications that increase the potential for drug-drug interactions (pDDIs). This study assessed pDDI prevalence in real-world nmCRPC patients treated with apalutamide, darolutamide, or enzalutamide. RESEARCH DESIGN AND METHODS: Castrated prostate cancer patients without metastases prior to androgen receptor inhibitor initiation were identified retrospectively via Optum Clinformatics Data Mart claims data (8/2019-3/2021). The top 100 concomitant medications were assessed for pDDIs. RESULTS: Among 1,515 patients (mean age: 77 ± 8 years; mean Charlson Comorbidity Index: 3 ± 3), 340 initiated apalutamide, 112 darolutamide, and 1,063 enzalutamide. Common concomitant medication classes were cardiovascular (80%) and central nervous system (52%). Two-thirds of the patients received ≥5 concomitant medications; 30 (30/100 medications) pDDIs were identified for apalutamide and enzalutamide each and 2 (2/100 medications) for darolutamide. Most pDDIs had risk ratings of C or D, but four for apalutamide were rated X. Approximately 58% of the patients on apalutamide, 5% on darolutamide, and 54% on enzalutamide had ≥1 identified pDDI. CONCLUSIONS: Results showed a higher frequency of pDDIs in patients receiving apalutamide and enzalutamide vs darolutamide. The impact of these could not be determined retrospectively. DDI risk should be carefully evaluated when discussing optimal therapy for patients with nmCRPC.

Next-Generation Sequencing Trends among Adult Patients with Select Advanced Tumor Types: A Real-World Evidence Evaluation.

There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health care claims database (January 1, 2014, to June 30, 2021; N = 63,209) examined NGS use trends over time. A modest increase in NGS was observed across tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%). A similar increase in NGS rates was also observed across key periods; however, rates in the final key period remained <10% for patients with breast, colorectal, head and neck, soft tissue sarcoma, and thyroid cancers, as well as central nervous system tumors. The median time to NGS from diagnosis was shortest among patients with non-small-cell lung cancer and longest for patients with breast cancer. Predictors of NGS varied by tumor type; test rates for minorities in select tumor types appeared comparable to the White population. Despite improving payer policies to expand coverage of NGS and molecular biomarker-based therapy approvals, NGS rates remained low across tumor types. Given the potential for improved patient outcomes with molecular biomarker-based therapy, further efforts to improve NGS rates are warranted.

Comparing costs and health care resource utilization between nmHSPC and mHSPC patients: a retrospective claims analysis.

BACKGROUND: Prostate cancer is common among men in the United States, and hormone sensitive-prostate cancer (HSPC) is the predominant etiology. However, there is a paucity of evidence documenting the financial impact of metastatic disease within this etiology. OBJECTIVE: To estimate the differences in health care resource utilization (HCRU) and costs for patients with nonmetastatic HSPC (nmHSPC) and metastatic HSPC (mHSPC) and their payers. METHODS: We conducted a retrospective cohort analysis using claims data from the IBM MarketScan databases from January 2016 to December 2019. HSPC was defined as having at least 1 inpatient services or 2 outpatient services claims with a prostate cancer diagnosis and a claim for androgen deprivation therapy use within 6 months of the initial diagnostic claim. Metastatic patients had a secondary diagnosis code of metastasis with their initial diagnostic claim. We compared mean 12-month HCRU, patient out-of-pocket (OOP), and payer costs between patients with nmHSPC and mHSPC using multivariable linear regression. RESULTS: 4,329 patients met the study inclusion criteria, 600 of which had mHSPC. Patients with mHSPC had more outpatient prescription fills (10.91 additional fills; 95% CI = 8.09-13.99) and outpatient services visits (10.61 additional visits; 95% CI = 8.38-13.04) but similar other HCRU. The overall 12-month costs of patients with mHSPC were significantly greater than patients with nmHSPC for patient OOP ($1,244; 95% CI = $1,004-$1,513) and payers ($113,725; 95% CI = $91,494-$141,127). CONCLUSIONS: Compared with patients with nmHSPC, individuals with mHSPC incur greater HCRU and significant personal and overall financial burden. DISCLOSURES: This study had no outside funding support. The authors have nothing to disclose.