Real-world patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer.

Background: Tucatinib is an oral human epidermal growth factor receptor 2 (HER2)-directed therapy approved in combination with trastuzumab and capecitabine for use in patients with previously treated HER2+ metastatic breast cancer (MBC) with/without brain metastases (BM). To inform clinical decision-making, it is important to understand tucatinib use in real-world clinical practice. We describe patient characteristics, treatment patterns, and clinical outcomes for tucatinib treatment in the real-world setting. Methods: This retrospective cohort study included patients diagnosed with HER2+ MBC (January 2017-December 2022) who received tucatinib treatment in a nationwide, de-identified electronic health record-derived metastatic breast cancer database. Patient demographics and clinical characteristics were described at baseline (prior to tucatinib initiation). Key outcomes included real-world time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and overall survival (rwOS). Results: Of 3,449 patients with HER2+ MBC, 216 received tucatinib treatment (n=153 with BM; n=63 without BM) and met inclusion criteria. Median (range) age of patients was 56 (28-84) years, 57.9% were White, and 68.5% had Eastern Cooperative Oncology Group performance status ≤1. Median (IQR) follow-up from start of tucatinib treatment was 12 (6-18) months. Among all patients who received tucatinib treatment, median (95% CI) rwTTD was 6.5 (5.4-8.8) months with 39.8% and 21.4% remaining on treatment at 12 and 24 months, respectively. Median (95% CI) rwTTNT was 8.7 (6.8-10.7) months. Patients who received the approved tucatinib triplet combination after ≥1 HER2-directed regimen in the metastatic setting had a similar median (95% CI) rwTTD (any line: 8.1 [5.7-9.5] months; second-line (2L) and third-line (3L): 9.4 [6.3-14.1] months) and rwTTNT (any line: 8.8 [7.1-11.8] months; 2L and 3L: 9.8 [6.8-14.1] months) to the overall population. Overall, median (95% CI) rwOS was 26.6 (20.2-not reached [NR]) months, with similar findings for patients who received the tucatinib triplet (26.1 [18.8-NR] months) and was NR in the subgroup limited to the 2L/3L population. Conclusion: Tucatinib treatment in the real-world setting was associated with a similar median rwTTD, rwTTNT, and rwOS as in the pivotal HER2CLIMB trial, with particular effectiveness in patients in the 2L/3L setting. These results highlight the importance of earlier use of tucatinib in HER2+ MBC.

Antiviral Use and Health Care Use Among US Patients With Rheumatoid Arthritis and Influenza in Three Influenza Seasons, 2016-2019.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are vulnerable to severe complications of influenza. We assessed whether health care resource use (HRU) and costs differed between patients with RA and influenza who received antiviral medication compared with matched patients with RA and influenza not receiving antiviral therapy. METHODS: This was a retrospective US health insurance claims analysis over three influenza seasons (each October to April) in 2016-2019. Adults with RA and a subsequent diagnosis of influenza were included. Treated patients (receiving antiviral influenza treatment within 2 days of diagnosis) and untreated patients were propensity score matched using baseline covariates. HRU and costs were assessed for inpatient, emergency department (ED), and outpatient visits and compared between cohorts using χ2 tests and t tests. RESULTS: After matching, 2638 treated and 1319 untreated patients were included. For treated versus untreated patients, the mean number of all-cause outpatient visits was 0.96 versus 1.21 during 14 days of follow-up (P < 0.001) and 1.94 versus 2.24 over 28 days (P = 0.001), respectively. Over 28 days, the mean number of all-cause ED visits was lower among treated (0.23) than untreated (0.30) patients (P = 0.042). The mean number of respiratory-related outpatient visits was significantly lower for treated versus untreated patients, and mean costs for these visits were $17.89 versus $35.27 over 14 days (P < 0.001) and $28.92 versus $48.77 over 28 days (P < 0.001) for treated versus untreated patients, respectively. CONCLUSION: Our findings demonstrate that prompt antiviral treatment after influenza diagnosis may reduce HRU and costs in patients with RA.

Baloxavir vs oseltamivir: reduced utilization and costs in influenza.

OBJECTIVES: To determine whether baloxavir use is associated with lower health care resource utilization (HCRU) and costs for secondary influenza complications post treatment compared with oseltamivir. STUDY DESIGN: Retrospective cohort study. METHODS: Patients filling a prescription for baloxavir or oseltamivir within 48 hours following an influenza-related outpatient visit were identified in the 2018-2019 influenza season from the US Truven MarketScan Research Databases and propensity matched 1:2 (baloxavir:oseltamivir). Outcomes were assessed 15 and 30 days after antiviral treatment and included all-cause, all respiratory-related, and select respiratory-related (influenza, asthma, chronic obstructive pulmonary disease, or infection) HCRU and costs. RESULTS: The study included 5080 baloxavir-treated and 10,160 matched oseltamivir-treated patients. All-cause emergency department (ED) visits and inpatient hospitalizations were lower in baloxavir-treated patients, with a statistically significant difference in the percentage hospitalized at 30 days (0.3% vs 0.5%; P = .04). ED visits for all or select respiratory-related conditions were significantly reduced with baloxavir (P < .01 for all comparisons). Mean per-patient cost savings at day 30 for all-cause, all respiratory-related, and select respiratory-related conditions were $79, $50, and $51, respectively, despite slightly higher prescription costs for baloxavir. In high-risk patients (baloxavir: n = 1958; oseltamivir: n = 3949), the incidence of ED visits was significantly lower for all respiratory-related and select respiratory-related conditions (P < .01); cost savings with baloxavir in the high-risk cohort were substantially greater than in the overall cohort. CONCLUSIONS: Treatment of patients with influenza with single-dose baloxavir was generally associated with lower HCRU and costs post treatment compared with oseltamivir, particularly in high-risk patients.

Work Productivity Outcomes Associated with Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis.

OBJECTIVE: This study evaluated work and activity impairment in patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs). METHODS: Data were obtained from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis. Patients with relapsing-remitting or secondary progressive MS who completed surveys in 2018 and 2019 and received ≥ 6 months of an eligible therapy, including OCR, injectable therapy, and oral therapy, were included. Outcomes were assessed using the patient-reported Work Productivity and Activity Impairment questionnaire. Doubly robust estimation, which combined propensity score weighting and regression modeling, was used to compare treatments, controlling for baseline clinical and demographic characteristics. RESULTS: This study included 630 patients (OCR, n = 90; injectable DMT, n = 224; oral DMT, n = 316) with a mean (standard deviation) age of 42 (11) years. A greater proportion of OCR-treated patients had an Expanded Disability Status Scale score of ≥ 3 at treatment initiation compared with those receiving oral and injectable DMTs (51 vs. 15% and 15%, respectively), and a smaller proportion of OCR-treated patients received treatment for ≥ 1 year (43 vs. 90% and 92%, respectively). OCR-treated patients had higher odds of employment [odds ratio (95% confidence interval) 3.4 (1.5-7.7) vs. oral DMT, 5.6 (2.6-12.0) vs. injectable DMT], lower overall work productivity loss [difference (95% confidence interval) - 10.0% (- 6.1 to - 15.0%) vs. oral DMT, - 13.0% (- 8.5 to - 17.0%) vs. injectable DMT] and lower activity impairment [difference (95% confidence interval) - 11% (- 7.1 to - 16.0%) vs. oral DMT, - 9.7% (- 5.0 to - 14.0%) vs. injectable DMT]. CONCLUSION: This real-world evidence suggests that patients with MS treated with OCR experience lower work and activity impairment than patients treated with other DMTs.

Multiple sclerosis (MS) is the most common progressive neurological disease in young adults. It typically starts between the ages of 20 and 40 years­arguably some of the most productive years of an individual's life­and it has a large impact on many aspects of everyday life for the rest of a person's life. The reduction in the ability to do routine activities, including working, results in a large economic burden. Disease-modifying treatments (DMTs) available for MS, particularly high-efficacy DMTs, have been shown to improve work productivity. This study looked at work and activity impairment using the Work Productivity and Activity Impairment Questionnaire in patients with MS who were treated with ocrelizumab (OCR) or other DMTs for ≥ 6 months. A total of 630 patients with relapsing­remitting MS (RRMS) or secondary progressive MS (SPMS) from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis were included in the study, including 90, 316 and 224 patients who completed ≥ 6 months of treatment with OCR, oral or injectable therapy. Compared with patients receiving oral or injectable DMTs, those receiving OCR had higher odds of employment [odds ratio (OR) vs. oral DMT 3.4; OR vs. injectable DMT 5.6], lower overall work productivity impairment (difference vs. oral DMT − 10%; difference vs. injectable DMT − 13%) and lower activity impairment (difference vs. oral DMT − 11%; difference vs. injectable DMT − 9.7%). These findings in patients with RRMS or SPMS being treated in the real world suggest that OCR may reduce the impact of MS disease on work productivity more than other DMTs.

Cost-Effectiveness of Cannabidiol Adjunct Therapy versus Usual Care for the Treatment of Seizures in Lennox-Gastaut Syndrome.

BACKGROUND: Cannabidiol (CBD) is a novel therapy for the treatment of Lennox-Gastaut Syndrome (LGS), a rare, treatment-refractory epileptic encephalopathy. Two pivotal trials found CBD 20 mg/kg/day conferred a reduction from baseline in median drop seizure frequency of 44% and 42%, respectively, compared with 22% and 17%, respectively, in the usual care arms. No economic evaluations have been published to date. This analysis assessed the cost effectiveness of CBD adjunct therapy compared with usual care alone in LGS from the US payer perspective. METHODS: We developed a lifetime horizon Markov decision analytic model. Efficacy, healthcare costs (2020 US$), and health state utilities were ascertained from published clinical trials, retrospective analyses, and time trade-off interviews conducted in the UK, respectively. Fifteen-year-old patients entering the model transitioned to states representing a percentage reduction in drop seizure frequency from baseline, where they remained until reverting back to baseline drop seizure frequency, or death. One-way and probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty, and scenario analyses investigated the impact of various assumptions. Costs and outcomes were discounted at 3%. RESULTS: Compared with usual care alone, CBD yielded 0.7 additional quality-adjusted life-years (QALYs) and $314,900 additional healthcare expenditure, resulting in $451,800 per QALY. Uncertainty in health state utilities were the largest contributor to uncertainty in the results. Results from the 5000-simulation probabilistic sensitivity analysis indicated a 0% chance of CBD being cost effective at a $150,000 per QALY willingness-to-pay threshold, with a 95% credible range for the incremental cost-effectiveness ratio of $325,300-$690,000 per QALY. CONCLUSION: CBD does not appear to be a cost-effective therapeutic option in LGS patients at a willingness-to-pay threshold of $150,000/QALY.

Economic Value of Pharmacogenetic Testing for Cancer Drugs with Clinically Relevant Drug-Gene Associations: A Systematic Literature Review.

BACKGROUND: Pharmacogenetic testing can provide predictive insights about the efficacy and safety of drugs used in cancer treatment. Although many drug-gene associations have been reported in the literature, the strength of evidence supporting each association can vary significantly. Even among the subgroup of drugs classified by the PharmGKB database to have a high or moderate level of evidence, there is limited information regarding the economic value of pharmacogenetic testing. OBJECTIVES: To: (a) summarize the available pharmacoeconomic evidence assessing the value of pharmacogenetic testing for cancer drugs with clinically relevant drug-gene associations; (b) determine the quality of the studies that contain this evidence; and (c) discuss the quality of this evidence with respect to the level of evidence of the drug-gene associations. METHODS: The PharmGKB database was used to identify cancer drugs with clinically relevant drug-gene associations graded high (1A, 1B) or moderate (2A, 2B). A systematic literature review was conducted using these drugs. Ovid MEDLINE and Embase databases were searched to identify cost-effectiveness, cost-utility, or cost-minimization studies comparing pharmacogenetic testing to an alternative. Cost and effect values from every relevant comparison within the studies were extracted, and the incremental cost-effectiveness ratio (ICER) was either extracted or calculated for each comparison. Quality assessment was conducted for each study using the Quality of Health Economic Studies (QHES) instrument. Qualitative synthesis was used to summarize the data. RESULTS: The search yielded 2,191 citations, of which 35 studies met the inclusion criteria. Pharmacoeconomic studies were available for the following drugs from the PharmGKB database: fluoropyrimidine, 6-mercaptopurine, irinotecan, carboplatin, cisplatin, erlotinib, gefitinib, cetuximab, panitumumab, and trastuzumab. The studies were conducted in Asia, Europe, Canada, the United States, and Mexico and reported cost-utility, cost-effectiveness, and cost-minimization outcomes. The mean QHES score was 80 (SD = 22) for the studies of drug-gene pairs with high (1A, 1B) and moderate (2A, 2B) levels of evidence (1A = 82, 1B = 93, 2A = 71, and 2B = 74). There was variation across studies in terms of reporting. 109 relevant comparisons were identified within the studies. Of those that reported cost per life-year or cost per quality-adjusted life-year (n = 58 comparisons), pharmacogenetic testing was dominant in 21% overall and 42%, 21%, 17%, and 5% of the comparisons in Asia, Europe, Canada, and the United States, respectively. Variability was observed in the ICER values regardless of geographic region or drug. Pharmacogenetic testing was cost saving in 17 of 19 cost-minimization comparisons and was favored most frequently when compared with genetically indiscriminate strategies containing the drug of interest. CONCLUSIONS: There was mixed evidence regarding the value of pharmacogenetic testing to guide cancer treatment. For future pharmacogenomic-related economic studies, we recommend prioritizing clinically relevant drug-gene associations and greater adherence to available best practice guidelines for conducting and reporting economic evaluation studies. DISCLOSURES: No outside funding supported this review. Part of Hussain's research time was supported by a Merit Review Award (I01 BX000545), Medical Research Service, U.S. Department of Veterans Affairs. Hussain also reports personal fees from Bristol-Myers Squibb, AstraZeneca, Novartis, Bayer HealthCare Pharmaceuticals, and France Foundation, outside the submitted work. Onukwugha reports grants from Pfizer and Bayer HealthCare Pharmaceuticals, along with advisory board fees from Novo Nordisk, outside the submitted work. Faruque, Neuberger, and Noh have nothing to disclose.