Real-world Trends, Rural-urban Differences, and Socioeconomic Disparities in Utilization of Narrow versus Broad Next-generation Sequencing Panels.

Advances in genetic technology have led to the increasing use of genomic panels in precision oncology practice, with panels ranging from a couple to hundreds of genes. However, the clinical utilization and utility of oncology genomic panels, especially among vulnerable populations, is unclear. We examined the association of panel size with socioeconomic status and clinical trial matching. We retrospectively identified 9,886 eligible adult subjects in the Mayo Clinic Health System who underwent genomic testing between January 1, 2016 and June 30, 2020. Patient data were retrieved from structured and unstructured data sources of institutional collections, including cancer registries, clinical data warehouses, and clinical notes. Socioeconomic surrogates were approximated using the Area Deprivation Index (ADI) corresponding to primary residence addresses. Logistic regression was performed to analyze relationships between ADI or rural/urban status and (i) use of genomic test by panel size; (ii) clinical trial matching status. Compared with patients from the most affluent areas, patients had a lower odds of receiving a panel test (vs. a single-gene test) if from areas of higher socioeconomic deprivation [OR (95% confidence interval (CI): 0.71 (0.61-0.83), P < 0.01] or a rural area [OR (95% CI): 0.85 (0.76-0.96), P < 0.01]. Patients in areas of higher socioeconomic deprivation were less likely to be matched to clinical trials if receiving medium panel tests [(OR) (95% CI): 0.69 (0.49-0.97), P = 0.03]; however, there was no difference among patients receiving large panel tests (P > 0.05) and rural patients were almost 2x greater odds of being matched if receiving a large panel test [(OR) (95% CI): 1.76 (1.21-2.55), P < 0.01]. SIGNIFICANCE: We identified socioeconomic and rurality disparities in the use of genomic tests and trial matching by panel size, which may have implications for equal access to targeted therapies. The lack of association between large panel tests and clinical trial matching by socioeconomic status, suggests a potential health equity impact, while removing barriers in access to large panels for rural patients may improve access to trials. However, further research is needed.

Copay assistance use and prescription abandonment across race, ethnicity, or household income levels for select rheumatoid arthritis and oral oncolytic medicines.

BACKGROUND: Disparities in prescription abandonment may exacerbate health inequities. Whether copay assistance is associated with changes in prescription abandonment across different patient groups is unknown. OBJECTIVE: To assess disparities in copay assistance use; prescription abandonment across race, ethnicity, or income; and association of copay use with prescription abandonment and whether it differs across race, ethnicity, or household income. METHODS: This pooled, cross-sectional study assessed claims-level prescription data linked to a consumer database containing information on race, ethnicity, and household income for commercially insured patients. The first prescription for rheumatoid arthritis (RA) or oral oncolytic medicines from 2016 to 2020 was included. Logistic regression models measured odds of copay assistance use (copay/discount cards or free-trial voucher) and prescription abandonment (prescription not filled within 30 days of health plan approval). Interaction terms for copay assistance use by race, ethnicity, and income were tested. RESULTS: The sample included 67,674 patients prescribed RA medications and 9,560 prescribed oral oncolytic medications. Copay assistance use across race, ethnicity, and income ranged from 28.2% to 31.1% (RA medicines) and 27.2% to 36.7% (oral oncolytic medicines). Among those prescribed RA medicines and not using copay assistance, Black/African American, Hispanic patients, and those with household incomes less than $50,000 were more likely to abandon prescriptions than White patients and patients with household incomes more than $200,000 (odds ratio [OR] [95% CI], P value: Black/African American: 1.17 [1.06-1.29], P < 0.01; Hispanic: 1.11 [1.01-1.22], P = 0.03; income <$50,000: 1.24 [1.11-1.37], P < 0.01). Among patients using oral oncolytic medicines and not using copay assistance, there was no racial or ethnic difference in prescription abandonment. Patients using oral oncolytics with household incomes less than $50,000 were more likely to use copay assistance (1.34 [1.12-1.61], P < 0.01), but also more likely to abandon their prescriptions if not using copay assistance (1.44 [1.12-1.85], P < 0.01). Copay assistance was associated with a 79% (RA) and 71% (oral oncolytics) lower odds of prescription abandonment (0.21 [0.19-0.24], P < 0.01; 0.29 [0.24-0.36], P < 0.01), which did not differ across race, ethnicity, or income levels (P > 0.05). CONCLUSIONS: Copay assistance has potential to narrow disparities in prescription abandonment for commercially insured Black/African American or Hispanic patients taking RA medicines and patients with household incomes less than $50,000; however, efforts to improve access to copay assistance are needed. Copay assistance, as a factor facilitating equal access to medicines, is an important consideration when evaluating policies that impact access to copay assistance programs. DISCLOSURES: Genentech, Inc., provided funding and support for this study. Dr Wong is an employee of Genentech, Inc., and shareholder of Roche, Inc. Ms Donahue, Mr Thiesen, and Mr Yeaw are employees of IQVIA.

Patient perspectives and use of copayment assistance during the COVID-19 pandemic.

BACKGROUND: Copay assistance programs provide financial assistance for patients to access medicines and may be one solution to addressing patient affordability, especially because of additional financial hardships due to the COVID-19 pandemic. These programs have been scrutinized by payers and policymakers, but there is little information on the patient perspective to inform these policy discussions. OBJECTIVE: To understand patients' perspectives and use of copay assistance during the COVID-19 pandemic. METHODS: A nationwide cross-sectional online descriptive patient survey was administered to collect data from adult recent medication users and caregivers. Data on demographics, skipping/stopping medications, current/past/future use of copay assistance, perceptions of copay assistance, and alternative actions taken if copay assistance was unavailable were collected. Descriptive analysis was conducted across the total sample, with subgroup analysis between those using and not using specialty pharmacies conducted on select measures. Analyses were conducted using STATA version 14.2. RESULTS: The final sample consisted of 1,001 adults aged 18 years or older. Twenty-eight percent of respondents reported currently or previously using copay assistance, with use higher among specialty pharmacy users vs non-specialty pharmacy users (46% vs 15%, P < 0.01). Copay assistance programs were viewed positively by most respondents (> 70%), with the proportion who viewed them "somewhat or more positively" during the COVID-19 pandemic growing significantly more among specialty pharmacy users than among non-specialty pharmacy users (53% vs 24%, P < 0.01). Respondents using copay assistance programs indicated they would take on more debt and cut back in other areas as alternatives to copay assistance, if unavailable. The alternative actions differed by specialty pharmacy use, with specialty pharmacy users reporting being more likely to use savings/retirement funds to help cover the cost (44% vs 22%, P < 0.01) or switch insurance plans (36% vs 22%, P = 0.03). CONCLUSIONS: Patients' positive perceptions of copay assistance programs have grown during the COVID-19 pandemic, and removing access to these programs may result in further debt and/or loss of savings for patients, especially for those using specialty medicines. Future patient-centric research is warranted and should be central to informing future policy discussions on the regulation of copay assistance programs. DISCLOSURES: W Wong and K Jinnett are employees of Genentech, Inc, and have stock in Roche (outside the submitted work). Research reported in this publication was supported by Genentech, Inc. Editorial services were provided by Esther Tazartes, MS, of Global Outcomes Group. These services were funded by Genentech, Inc.

Modeling the Ex Ante Clinical Real Option Value in an Innovative Therapeutic Area: ALK-Positive Non-Small-Cell Lung Cancer.

OBJECTIVES: A drug that improves survival and/or disease progression can create real option value (ROV)-the additional health gain from future innovations enabled by a longer survival. ROV can be a relevant consideration for both clinical and payer decision-makers. We aimed to estimate the ex ante ROV for first-line (1L) alectinib in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). METHODS: We developed a Markov model to estimate life-years (LYs) and quality-adjusted life-years (QALYs) gained with 1L alectinib versus 1L crizotinib due to potential future second-line (2L) drugs. Transition probabilities were derived from the phase 3 trial of 1L alectinib and phase 2 trial of 2L brigatinib. We identified drugs being studied in phase 2 and 3 trials in ALK-positive NSCLC at the time of alectinib's 1L approval and projected the likelihood and timing of their arrival and their potential efficacy based on publicly available data. RESULTS: The discounted incremental LYs and QALYs for alectinib increased by 12.9% (95% CR - 2.96%, 34.82%; 1.25 vs. 1.11) and 11.2% (95% CR - 2.14%, 29.29%; 1.03 vs. 0.92), respectively, after accounting for ROV. The incremental ROV of alectinib was sensitive to the projected efficacy of future drugs, uptake level, and the hazard ratio of progression-free survival of alectinib (vs. crizotinib). CONCLUSIONS: Ex ante ROV can be a significant value consideration in therapeutic areas with high levels of expected innovation. The potential efficacy of future drugs and incremental survival with alectinib at the projected time of arrival are important considerations in assessing ROV.

Impact of co-pay assistance on patient, clinical, and economic outcomes.

OBJECTIVES: Patient assistance programs (eg, co-pay assistance) may reduce patients' out-of-pocket costs for prescription medicines, providing financial assistance to access medicines for reduced or no cost. A literature review to identify peer-reviewed articles on studies evaluating the impact of co-pay assistance on clinical, patient, and economic outcomes was conducted. STUDY DESIGN: A literature review was conducted by searching Embase and MEDLINE. METHODS: The population of interest was patients who had received co-pay assistance; the intervention was co-pay assistance; comparator was no co-pay assistance; and outcomes were treatment adherence, compliance, discontinuation, interruption, barriers to adherence, and specific therapeutic outcomes. Articles from the United States published between January 2015 and June 2021 were included. RESULTS: A total of 1249 initial articles were identified, of which 19 published articles representing 12 studies were included. Most studies were retrospective claims analyses (n = 10); there was also 1 randomized controlled trial and 1 prospective and observational study. One article assessed the association between co-pay assistance and patient-reported outcomes, 7 explored the relationship between co-pay assistance and clinical outcomes, and 6 assessed the impact of policy/program changes on co-pay assistance. Co-pay assistance was associated with improved treatment persistence/adherence across various diseases, with limited indirect evidence of this translating into clinical outcomes improvements. Lack of long-term outcomes and uncertainty around program sustainment from co-pay assistance programs are limitations. CONCLUSIONS: Limited evidence suggests a potential link between co-pay assistance and clinical outcomes; future research addressing study design challenges in measuring the effects of co-pay assistance is needed.

Associations Between Medicaid Insurance, Biomarker Testing, and Outcomes in Patients With Advanced NSCLC.

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.

Alignment of health plan coverage policies for somatic multigene panel testing with clinical guidelines in select solid tumors.

Aim: Commercial plan coverage policies for multigene panel tests may vary and could result in geographic variation in coverage due to the fragmented nature of the commercial insurance market. This study aimed to characterize the alignment of multigene panel tests coverage policies to that of clinical guidelines, overall and by state. Materials & methods: We reviewed NCCN Guidelines® for four tumors. Public coverage policies were identified via web search. Payer policies included those with the largest or second largest number of commercial lives in each state. Policies were classified as 'more restrictive' or 'consistent' with the guidelines. Results: Of 38 plans/policies reviewed, 71% were classified as 'more restrictive' than the guidelines, with variation in the number of commercial lives by state. Among these, 52% restricted on panel size and 63% restricted in all or select tumors. Conclusion: Most coverage policies were more restrictive. Clinical guideline clarity and state policies may improve alignment to guidelines and geographic variations.

The level of coverage provided by commercial plan policies for tests that simultaneously assess multiple genes for cancer (multigene panel tests) may vary, and the availability of these tests differs depending on geographic location. This may be due to the variable nature of the commercial insurance market. This study aimed to understand how well aligned the coverage for multigene panel tests provided by insurance policies is with recommendations from clinical guidelines, both overall and by US state. NCCN Guidelines^® for four cancer types were reviewed and public insurance coverage policies were identified via internet searches. The insurance policies included those with the largest or second largest number of commercial lives in each state. Policies were judged to be either 'more restrictive' or 'consistent' with the clinical guidelines. Of the 38 plans/policies we reviewed, almost three-quarters (71%) were judged to be 'more restrictive' than the guidelines, with differences in the number of commercial lives by state. About half (52%) were restricted on the number of genes to be tested and almost two-thirds (63%) restricted in all or select types of cancer. We found that most insurance policies were more restrictive than the guidelines ­ therefore covering fewer genes in each test, a different set of genes in each test or restricted to certain types of cancer. Clearer clinical guideline and state policies may help to improve alignment to guidelines and geographic differences.

Real-world adherence and persistence with anaplastic lymphoma kinase inhibitors in non-small cell lung cancer.

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.

Trends in Use of Next-Generation Sequencing in Patients With Solid Tumors by Race and Ethnicity After Implementation of the Medicare National Coverage Determination.

Importance: In March 2018, Medicare issued a national coverage determination (NCD) for next-generation sequencing (NGS) to facilitate access to NGS testing among Medicare beneficiaries. It is unknown whether the NCD affected health equity issues for Medicare beneficiaries and the overall population. Objective: To examine the association between the Medicare NCD and NGS use by insurance types and race and ethnicity. Design, Setting, and Participants: A retrospective cohort analysis was conducted using electronic health record data derived from a real-world database. Data originated from approximately 280 cancer clinics (approximately 800 sites of care) in the US. Patients with advanced non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), or advanced melanoma diagnosed from January 1, 2011, through March 31, 2020, were included. Exposure: Pre- vs post-NCD period. Main Outcomes and Measures: Patients were classified by insurance type and race and ethnicity to examine patterns in NGS testing less than or equal to 60 days after diagnosis. Difference-in-differences models examined changes in average NGS testing in the pre- and post-NCD periods by race and ethnicity, and interrupted time-series analysis examined whether trends over time varied by insurance type and race and ethnicity. Results: Among 92 687 patients with aNSCLC, mCRC, mBC, or advanced melanoma, mean (SD) age was 66.6 (11.2) years, 51 582 (55.7%) were women, and 63 864 (68.9%) were Medicare beneficiaries. The largest racial and ethnic categories according to the database used and further classification were Black or African American (8605 [9.3%]) and non-Hispanic White (59 806 [64.5%]). Compared with Medicare beneficiaries, changes in pre- to post-NCD NGS testing trends were similar in commercially insured patients (odds ratio [OR], 1.03; 95% CI, 0.98-1.08; P = .25). Pre- to post-NCD NGS testing trends increased at a slower rate among patients in assistance programs (OR, 0.93; 95% CI, 0.87-0.99; P = .03) compared with Medicare beneficiaries. The rate of increase for patients receiving Medicaid was not statistically significantly different compared with those receiving Medicare (OR, 0.92; 95% CI, 0.84-1.01; P = .07). The NCD was not associated with statistically significant changes in NGS use trends by racial and ethnic groups within Medicare beneficiaries alone or across all insurance types. Compared with non-Hispanic White individuals, increases in average NGS use from the pre-NCD to post-NCD period were 14% lower (OR, 0.86; 95% CI, 0.74-0.99; P = .04) among African American and 23% lower (OR, 0.77; 95% CI, 0.62-0.96; P = .02) among Hispanic/Latino individuals; increases among Asian individuals and those with other races and ethnicities were similar. Conclusions and Relevance: The findings of this study suggest that expansion of Medicare-covered benefits may not occur equally across insurance types, thereby further widening or maintaining disparities in NGS testing. Additional efforts beyond coverage policies are needed to ensure equitable access to the benefits of precision medicine.

Modeling the Ex Post Real Option Value in Metastatic Melanoma Using Real-World Data.

OBJECTIVES: Real option value (ROV) is created when a drug enables a patient to live long enough to benefit from a future innovation. Few studies have quantified ROV in the real world. We aimed to estimate the ex post ROV for ipilimumab in metastatic melanoma using real-world data (RWD). METHODS: We developed a framework for calculating ROV using RWD, accounting for the health gain in the standard therapy arm and the uptake of future innovations. A Markov model was developed to estimate the quality-adjusted life-years (QALYs) gained with ipilimumab compared with chemotherapy for patients with or without subsequent cancer immunotherapy (CIT). A nationwide electronic health record-derived, deidentified database was used to estimate survival and uptake of CIT. RESULTS: The incremental QALYs gained for ipilimumab compared with chemotherapy without subsequent CIT were 1.74. With subsequent CIT, the incremental QALYs compared with chemotherapy increased by 0.92, 0.60, 0.33, 0.18, 0.10, and 0.02 when CIT became available 0, 3, 6, 9, 12, and 24 months after the initiation of first-line treatment, respectively. The results were most sensitive to the survival benefit of ipilimumab, the survival benefit of subsequent CIT, and the uptake of CIT. CONCLUSIONS: This is the first study to estimate ex post ROV using RWD. The ex post ROV was between 1% and 54% of conventional value for patients who received a diagnosis within 2 years before CIT availability. Further studies are needed to understand ROV in other disease areas, particularly those with longer survival times.

Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in ROS1+ NSCLC.

Aim: Generating direct comparative evidence in prospective randomized trials is difficult for rare diseases. Real-world cohorts may supplement control populations. Methods: Entrectinib-treated adults with advanced ROS1 fusion-positive NSCLC (n = 94) from Phase I/II trials (ALKA-372-001 [EudraCT2012-00148-88], STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]) were compared with a real-world crizotinib-treated cohort (n = 65). Primary end point, time-to-treatment discontinuation (TTD); secondary end points, PFS and OS. Results: Median (95% CI) weighted TTD: 12.9 (9.9-17.4) months for entrectinib; 8.8 (6.2-9.9) months for crizotinib (weighted hazard ratio: 0.72 [0.51-1.02]). Median OS with entrectinib was not reached, weighted median OS with crizotinib was 18.5 (15.1-19.9) months. Conclusion: Entrectinib administered in clinical trials may be associated with longer TTD than a real-world crizotinib population.

Real-world evidence for option value in metastatic melanoma.

BACKGROUND: The concept of real option value (ROV) suggests there is added value in treatments that extend life because they enable a patient to live long enough to benefit from future innovative treatments. Real-world evidence of this novel value element is scant, limiting its consideration in formal value assessments. OBJECTIVE: To calculate the ROV in clinical practice of ipilimumab for treatment of advanced melanoma, with evaluation of survival until availability of cancer immunotherapy (CIT). METHODS: This was a retrospective analysis of electronic health records from a US nationwide deidentified database including data from approximately 280 cancer clinics. Participants were patients with advanced or metastatic melanoma diagnosed after January 1, 2011, who initiated treatment before April 19, 2015, and were treated with first-line and second-line ipilimumab or chemotherapy, up to availability of CIT. The proportions of patients surviving and receiving CIT and overall survival by line of therapy were calculated. Baseline demographics were used to weight Kaplan-Meier curves using stabilized inverse probability of treatment weighting. ROV was estimated for patients receiving first-line or second-line ipilimumab with or without subsequent CIT and first-line or second-line chemotherapy with or without subsequent CIT. RESULTS: Overall, 721 patients were included in the study, with a total sample size of 733 (12 patients in both groups). For first-line ipilimumab, 50% of patients survived to the availability of CIT, while only 18% of first-line chemotherapy users survived to the same date. For second-line ipilimumab, 37% of patients survived to availability of CIT vs 21% of patients using second-line chemotherapy. 45% of first-line ipilimumab and 52% of second-line ipilimumab patients who survived to the availability date received CIT. ROV for first-line ipilimumab averaged 3.7 months of additional survival, while those who initiated second-line ipilimumab averaged 4.8 months. The combined estimated ROV was 3.9 months. CONCLUSIONS: This study provides real-world evidence of ROV and adds to the growing literature that may support inclusion of this novel value concept for innovative therapies alongside more traditional measures of value. Further evaluation of ROV in clinical areas with varying survival and innovation is warranted. DISCLOSURES: This study was funded by Genentech, Inc., which was involved in conducting the study. Wong and To are employees of Genentech, Inc. Veenstra, Garrison, Li, and Lee have served as consultants to Genentech, Inc. Data were presented at ISPOR 2021; May 17-20, 2021; as a virtual podium presentation.

Novel Approach Using Administrative Claims to Evaluate Trends in Oncology Multigene Panel Testing for Patients Enrolled in Medicare Advantage Health Plans.

PURPOSE: To develop an approach to identify and evaluate recent use of multigene panel testing over time. METHODS: We conducted a retrospective database analysis using medical and pharmacy claims data. Medicare Advantage Prescription Drug Plan members diagnosed with select malignant solid tumors were identified. The pattern of somatic genetic testing for each patient was evaluated from January 2016 through December 2018. Tests were classified by the number of genes tested in the panel: < 50 (small or medium) and ≥ 50 (large). RESULTS: An initial feasibility study using our novel approach for identifying panel tests resulted in 2.4 and 1.2 times more large and medium panels, respectively, identified compared with using procedure codes alone. A total of 121,675 eligible patients were identified, with 131,915 unique cancer cases. Overall, 5,457 (4.5%) patients received any panel test from 2016 to 2018. We found the number of tests performed each quarter increased from 238 in Q1 of 2016 to 755 in Q4 of 2018. The highest number of cases were genitourinary cancers; however, the highest proportion of cancer-related genetic testing was among patients with respiratory cancer. Across all tumor types, the proportion of large-panel tests performed as a function of all multigene panel tests increased from 20.7% of tests in Q1 of 2016 to 46.4% of tests in Q4 of 2018. The three cancer categories with the highest count of cancer-related panel tests, respiratory cancer, GI cancer, and female reproductive cancer, had a consistently greater proportion receiving a panel test at any point postindex. CONCLUSION: Across a variety of cancers, use of somatic, large-panel cancer-related genetic testing, as a proportion of all somatic cancer-related genetic testing, increased from 2016 to 2018, although testing overall was low.

Association Between Medicare's National Coverage Determination and Utilization of Next-Generation Sequencing.

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.

Estimated Impact of Public and Private Sector COVID-19 Diagnostics and Treatments on US Healthcare Resource Utilization.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has imposed a considerable burden on the United States (US) health system, with particular concern over healthcare capacity constraints. METHODS: We modeled the impact of public and private sector contributions to developing diagnostic testing and treatments on COVID-19-related healthcare resource use. RESULTS: We estimated that public sector contributions led to at least 30% reductions in COVID-19-related healthcare resource utilization. Private sector contributions to expanded diagnostic testing and treatments led to further reductions in mortality (- 44%), intensive care unit (ICU) and non-ICU hospital beds (- 30% and - 28%, respectively), and ventilator use (- 29%). The combination of lower diagnostic test sensitivity and proportions of patients self-isolating may exacerbate case numbers, and policies that encourage self-isolating should be considered. CONCLUSION: While mechanisms exist to facilitate research, development, and patient access to diagnostic testing, future policies should focus on ensuring equitable patient access to both diagnostic testing and treatments that, in turn, will alleviate COVID-19-related resource constraints.

Value of Precision Medicine in Advanced Non-Small Cell Lung Cancer: Real-World Outcomes Associated with the Use of Companion Diagnostics.

BACKGROUND: Companion diagnostic (CDx) testing for patients with advanced non-small cell lung cancer (aNSCLC) identifies patients more likely to benefit from biomarker-driven treatments. METHODS: Patients with nonsquamous cell (non-Sq) aNSCLC from the Flatiron Health database (diagnosed January 1, 2011-May 31, 2018) who had CDx testing were compared with those who had no reported evidence of testing. The association between CDx testing and overall survival was evaluated by unadjusted and adjusted Cox proportional hazards regression models. Logistic regression analysis identified characteristics associated with CDx testing. The revised modified Lung Cancer Prognostic Index and other factors identified a priori were included in the adjusted models. RESULTS: A total of 17,555 patients with non-Sq aNSCLC (CDx, n = 14,732; no CDx, n = 2,823) with mean ± SD age of 67.2 ± 10.0 years were included. Most were insured (91.7%) and white (67.1%). Asian patients and those who were never-smokers were more likely to undergo CDx testing. Those with CDx testing lived longer than those without (median [95% confidence interval (CI)] survival, 13.04 [12.62-13.40] vs. 6.01 [5.72-6.24] months) and had a decreased mortality risk (adjusted hazard ratio [95% CI], 0.72 [0.69-0.76]). A survival advantage was also seen for patients with CDx testing who received biomarker-driven first-line therapy. CONCLUSION: Patients with non-Sq aNSCLC who had CDx testing had a greater survival benefit than those without, supporting broader use of CDx testing in routine clinical practice to identify patients more likely to benefit from precision medicine. IMPLICATIONS FOR PRACTICE: Companion diagnostic (CDx) testing coupled with biomarker-driven treatment offers a greater survival benefit for patients with advanced non-small cell lung cancer (aNSCLC). In this study, patients with nonsquamous aNSCLC from Flatiron Health, a large, real-world oncology database, with CDx testing had a reduced mortality risk and lived longer than patients without reported evidence of CDx testing; those who received biomarker-driven therapy as their first line of treatment were likely to survive three times longer than those who did not. These results demonstrate the clinical utility of CDx testing as the first step in treating nonsquamous aNSCLC in real-world clinical practice.

Real-World Clinical and Economic Outcomes and the Role of Bevacizumab in Patients With Non-Small-Cell Lung Cancer With Liver Metastases.

PURPOSE: Liver metastases are associated with poor outcomes in patients with advanced non-small-cell lung cancer (aNSCLC). Nevertheless, the vasculature in the liver microenvironment may be conducive to the use of antiangiogenesis inhibitors to potentially improve outcomes. Limited real-world clinical and economic data are currently available for this patient subpopulation. METHODS: Two retrospective cohort analyses were conducted using data from an electronic health record (n = 14,209) and a claims database (n = 9,017). Patients with aNSCLC with and without liver metastases were identified in each database. Patients with baseline liver metastases in the electronic health record database were further categorized into two subgroups-those who had or had not received bevacizumab-containing regimens. Multivariable Cox proportional hazards regression models were used to adjust for baseline characteristics to evaluate the effect of treatment of bevacizumab. RESULTS: Liver metastases were associated with significantly poorer survival (median overall survival, 6.3 months v 10.1 months) and higher costs and health care resource utilization-total per-patient-per-month costs of $27,589 versus $19,607. Cost differences were primarily driven by inpatient costs, including a two-fold increase in hospitalizations and a 1.7-fold higher mean length of stay. Treatment with bevacizumab was associated with improved survival. Whereas overall survival improved in patients with and without baseline liver metastases who received bevacizumab, the relative survival benefit was greater in patients with liver metastases (hazard ratio, 0.63 [95% CI, 0.50 to 0.81] v hazard ratio, 0.80 [95% CI, 0.74 to 0.86]). CONCLUSION: Patients with aNSCLC with liver metastases have poorer survival and a higher cost and health care resource utilization burden. Bevacizumab was associated with a survival benefit in patients with aNSCLC with liver metastases.

Are National Comprehensive Cancer Network Evidence Block Affordability Ratings Representative of Real-World Costs? An Evaluation of Advanced Non-Small-Cell Lung Cancer.

PURPOSE: The National Comprehensive Cancer Network (NCCN) developed the Evidence Blocks framework to assess the value of oncology regimens. This study characterizes the relationship between real-world costs and NCCN affordability ratings (ARs) for advanced non-small-cell lung cancer (aNSCLC) treatments. METHODS: Using the MarketScan and PharMetrics Plus databases, we identified patients treated between 2012 and 2017 with an aNSCLC regimen evaluated by the NCCN Evidence Blocks. We estimated adjusted mean total per-patient-per-month (PPPM) costs and drug costs for each regimen using a log-linked gamma generalized linear model. Weighted regression was used to examine the correlation between adjusted mean PPPM costs per regimen and NCCN AR. RESULTS: A total of 25,162 patients with aNSCLC (mean age, 63 years [standard deviation, 10 years]; 52% male) had identifiable regimens. Mean total PPPM cost by therapeutic class ranged from $16,824 for epidermal growth factor receptors to $41,815 for immunotherapy-based treatment. Epidermal growth factor receptor and anaplastic lymphoma kinase inhibitor treatment had lower ARs compared with generic chemotherapy. No therapy was listed as AR group 5 (least expensive). In pairwise comparisons, AR group 1 had significantly higher PPPM total costs compared with AR groups 2 and 4. There were no significant differences in PPPM total cost among AR groups 2, 3, and 4. CONCLUSION: Real-world aNSCLC treatment costs are often inconsistent with the NCCN ARs. Given that NCCN Evidence Blocks are intended to inform provider-patient discussions and other decision support resources, such as the NCCN Categories of Preference, our results suggest that the NCCN ARs require further refinement and validation.

Predictors, Resource Utilization, and Short-term Costs of Laser Trabeculoplasty Versus Medication Management in Open-Angle Glaucoma.

PURPOSE: Adjunctive laser trabeculoplasty (LT) is an alternative to topical medications for open-angle glaucoma (OAG). The purpose was to: (1) identify predictors of LT vs glaucoma medication treatment; and (2) estimate the resource utilization and short-term costs associated with LT vs medication management. DESIGN: Retrospective administrative claims analysis. METHODS: Medical and pharmacy claims data between 2007 and 2012 were analyzed to identify prostaglandin analogue monotherapy OAG patients with an index date LT claim or second medication class claim. Patients were followed for 12 months pre-index and 24 months post-index. Predictive LT attributes included age, sex, employment status, medication adherence, comorbidity status, and geographic region. Short-term costs included glaucoma-specific and comprehensive healthcare encounters. Cohort comparisons were analyzed using χ(2) and Student t tests, logistic regression (predictive), and generalized linear models (cost). RESULTS: The study included 4743 LT and 16 484 medication patients. Baseline demographics were similar but significant differences were identified for comorbidities, adherence, and geography. Younger age (odds ratio [OR]: 1.21; P < .001), low adherence (OR: 1.18; P = .001), high comorbidities (OR: 1.12; P = .006), and region (OR: 1.50; P < .001) significantly predicted LT receipt. Within LT patients, 60% did not have a pharmacy claim 45 days post-index; by 2 years, this reduced to 20%. LT attributed significantly higher medical ($2684 vs $1980; P < .0001), lower pharmacy ($807 vs $1467; P < .0001), and greater overall costs ($3441 vs $3408; P = .325). CONCLUSIONS: Poor adherence, younger age, and more comorbidities were predictors of receiving LT. Despite the potential for LT to address adherence, most patients had a medication claim within 2 years. Overall, LT does not provide glaucoma-specific cost savings.

An adherence based cost-consequence model comparing bimatoprost 0.01% to bimatoprost 0.03%.

OBJECTIVES: Estimate the long-term direct medical costs and clinical consequences of improved adherence with bimatoprost 0.01% compared to bimatoprost 0.03% in the treatment of glaucoma. METHODS: A cost-consequence model was constructed from the perspective of a US healthcare payer. The model structure included three adherence levels (high, moderate, low) and four mean deviation (MD) defined health states (mild, moderate, severe glaucoma, blindness) for each adherence level. Clinical efficacy in terms of IOP reduction was obtained from the randomized controlled trial comparing bimatoprost 0.01% with bimatoprost 0.03%. Medication adherence was based on observed 12 month rates from an analysis of a nationally representative pharmacy claims database. Patients with high, moderate and low adherence were assumed to receive 100%, 50% and 0% of the IOP reduction observed in the clinical trial, respectively. Each 1 mmHg reduction in IOP was assumed to result in a 10% reduction in the risk of glaucoma progression. Worse glaucoma severity health states were associated with higher medical resource costs. Outcome measures were total costs, proportion of patients who progress and who become blind, and years of blindness. Deterministic sensitivity analyses were performed on uncertain model parameters. RESULTS: The percentage of patients progressing, becoming blind, and the time spent blind slightly favored bimatoprost 0.01%. Improved adherence with bimatoprost 0.01% led to higher costs in the first 2 years; however, starting in year 3 bimatoprost 0.01% became less costly compared to bimatoprost 0.03% with a total reduction in costs reaching US$3433 over a lifetime time horizon. Deterministic sensitivity analyses demonstrated that results were robust, with the majority of analyses favoring bimatoprost 0.01%. Application of 1 year adherence and efficacy over the long term are limitations. CONCLUSIONS: Modeling the effect of greater medication adherence with bimatoprost 0.01% compared with bimatoprost 0.03% suggests that differences may result in improved economic and patient outcomes.