Health state utility values (HSUVs) are an important input to economic evaluations and the choice of HSUV can affect the estimate of relative cost-effectiveness between interventions. This systematic review identified utility scores for patients with metastatic non-small cell lung cancer (mNSCLC), as well as disutilities or utility decrements relevant to the experience of patients with mNSCLC, by treatment line and health state. The MEDLINE®, Embase and Cochrane Library databases were systematically searched (September 2016) for publications describing HSUVs in mNSCLC in any treatment line. The EQ-5D website, the School of Health and Related Research Health Utilities Database (ScHARRHUD) and major pharmacoeconomic and clinical conferences in 2015–2016 were also queried. Studies in adults with previously treated mNSCLC were selected for further analysis. The information extracted included study design, description of treatment and health state, respondent details, instrument and tariff, HSUV or (dis) utility decrement estimates, quality of study, and appropriateness for use in economic evaluations. Of 1883 references identified, 36 publications of 34 studies were included: 19 reported EQ-5D scores; eight reported HSUVs from valuations of vignettes made by members of the public using standard gamble (SG) or time trade-off (TTO); two reported SG or TTO directly elicited from patients; two reported EQ-5D visual analogue scale scores only; one reported Assessment of Quality of Life instrument scores; one reported HSUVs for caregivers to patients with mNSCLC using the 12-item Short-Form Health Survey; and one estimated HSUVs based on expert opinion. The range of HSUVs identified for comparable health states showed how differences in study type, tariff, health state and the measures used can drive variation in HSUV estimates. This systematic review provides a set of published HSUVs that are relevant to the experience of adult patients previously treated for mNSCLC. Our review begins to address the challenge of identifying reliable estimates of utility values in mNSCLC that are suitable for use in economic evaluations, and also highlights how varying estimates result from differences in methodology.

Introduction: For patients with late-stage (metastatic) breast cancer, the impact of treatment on health-related quality of life is a key factor in decision-making. A systematic review was conducted to identify health state utility values (HSUVs) for late-stage breast cancer, derived using methods preferred by health technology assessment (HTA) agencies, by treatment line. The aim was to generate a list of HSUVs, that could help to justify the values used to populate cost-utility models. Areas covered: Ten electronic databases, international congress websites and online HSUV databases were searched (January 1995–May 2014) for HSUVs for adults with late-stage breast cancer that had been derived from methods favoured by HTA agencies. Publications were included only if they reported studies that originated HSUVs. Expert commentary: Large numbers of HSUVs are available for late-stage breast cancer in the published literature. Contrary to expectations, the HSUVs reported in the literature vary greatly for some health states. As a result, the choice of HSUV can have considerable implications for the outcomes of economic evaluations. Standardization of HSUV methodology is expected to reduce variability; however, further research is recommended for assessing the sensitivity of generic preference-based measures in late-stage (metastatic) breast cancer.

Purpose: In the absence of head-to-head trial data, network meta-analysis (NMA) was used to compare trastuzumab emtansine (T-DM1) with other approved treatments for previously treated patients with unresectable or metastatic HER2-positive breast cancer (BC). Methods: Systematic reviews were conducted of published controlled trials of treatments for unresectable or metastatic HER2-positive BC with early relapse (≤ 6 months) following adjuvant therapy or progression after trastuzumab (Tras) + taxane published from January 1998 to January 2018. Random-effects NMA was conducted for overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety endpoints. Results: The NMA included regimens from seven randomized controlled trials: T-DM1 and combinations of Tras, capecitabine (Cap), lapatinib (Lap), neratinib, or pertuzumab (Per; unapproved). OS results favored T-DM1 over approved comparators: hazard ratio (HR) (95% credible interval [95% CrI]) vs Cap 0.68 (0.39, 1.10), LapCap 0.76 (0.51, 1.07), TrasCap 0.78 (0.44, 1.19). PFS trends favored T-DM1 over all other treatments: HR (95% CrI) vs Cap 0.38 (0.19, 0.74), LapCap 0.65 (0.40, 1.10), TrasCap 0.62 (0.34, 1.18); ORR with T-DM1 was more favorable than with all approved treatments. In surface under cumulative ranking curve (SUCRA) analysis T-DM1 ranked highest for all efficacy outcomes. Discontinuation due to adverse events was less likely with T-DM1 than with all comparators except neratinib. In general, gastrointestinal side effects were less likely and elevated liver transaminases and thrombocytopenia more likely with T-DM1 than with comparators. Conclusions: The efficacy and tolerability profiles of T-DM1 are generally favorable compared with other treatments for unresectable or metastatic HER2-positive BC.

Information regarding the comparative efficacy of first-generation receptor tyrosine kinase inhibitors is limited. This matching-adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)) and entrectinib (ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267)) were used. Adults (≥18 years) across trials were matched on available baseline characteristics. Outcomes evaluated included overall response rate (ORR), complete response (CR) rate, duration of response (DoR), overall survival (OS), progression-free survival (PFS), any serious treatment-related adverse events of grade ≥ 3 (TRAEs), and TRAEs leading to treatment discontinuation. The MAIC included 74 patients from entrectinib trials and 117 and 147 patients for the larotrectinib efficacy and safety populations, respectively. Post-matching, larotrectinib was associated with a significantly longer median duration of OS than entrectinib (p < 0.05) and a numerically longer median PFS (p = 0.07). ORR was similar for both agents (p = 0.63). The CR rate was higher (p < 0.05) and the DoR was longer for larotrectinib (p < 0.05). Safety outcomes were comparable and low for both treatments. Results were consistent in sensitivity analyses. These findings suggest favorable efficacy for larotrectinib and comparable safety profiles versus entrectinib in treating tropomyosin receptor kinase fusion cancer.

Background Spinal muscular atrophy (SMA) is a rare neuromuscular disease that affects motor neurons, resulting in progressive skeletal muscle weakness and atrophy. Objective The aim was to understand the value patients with SMA and caregivers place on treatment attributes and to estimate health utilities for SMA treatment outcomes from a general public sample. Methods Two discrete choice experiments were designed to elicit treatment preferences and health utilities, respectively. Patients with Type 2 and non-ambulatory Type 3 SMA, caregivers of patients with SMA and a general public sample in the UK completed the surveys. Patients and caregiver participants were recruited through patient associations. General public participants were recruited via a survey recruitment panel. Attributes included motor function, breathing function, treatment administration, treatment reactions, eyesight monitoring, contraception (patients only) and overall survival (general public only). Clustered conditional logit models were used to estimate treatment preferences, and marginal rates of substitution were used to estimate disutilities. Results Adult patients (n = 84) were twice as likely to choose a treatment with improved (vs. stable) motor and breathing function and four to five times less likely to choose a treatment with deteriorated (vs. stable) motor and breathing function as a treatment outcome. Caregivers (n = 83) were three to nine times more likely to choose improved and two to four times less likely to choose deteriorated (vs. stable) motor and breathing function. Both patients and caregivers preferred oral over intrathecal treatment. Treatment reactions, eyesight monitoring or contraception had no significant effect on patient choices. Conversely, caregivers preferred avoidance of treatment reactions. General public data (n = 506) yielded disutilities for unable to sit (− 0.408), need for > 16 h daily mechanical breathing support (− 0.304) and intrathecal therapy (− 0.071). Conclusions Study results show the importance of motor and breathing function to patients and caregivers, and an oral treatment preference. Disutilities (decrements to utility) were substantial for SMA disease outcomes and care aspects.

PURPOSE: Evidence suggests that neurotrophic tyrosine receptor kinase ( NTRK) gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult and pediatric tumor types. However, despite robust clinical response to tyrosine receptor kinase (TRK) inhibitors, the natural history and prognostic implications of NTRK fusions in solid tumors are poorly understood. It is important to evaluate their prognostic significance on survival to provide some context to the clinical effectiveness observed in clinical trials of TRK-targeted therapies. METHODS: A systematic literature review was conducted in Medline, Embase, Cochrane, and PubMed to identify studies comparing the overall survival (OS) of patients with NTRK fusion–positive ( NTRK+) versus NTRK fusion–negative ( NTRK–) tumors. Five retrospective matched case-control studies published before 11 August 2022 were assessed for inclusion, and three were selected for the meta-analysis (sample size: 69 NTRK+, 444 NTRK–). Risk of bias was assessed using the Risk of Bias Assessment tool for Non-randomized Studies tool. The pooled hazard ratio (HR) was estimated using a Bayesian random-effects model. RESULTS: In the meta-analysis, the median follow-up ranged from 2 to 14 years and the median OS was between 10.1 and 12.7 months (where reported). Comparing patients with tumors NTRK+ and NTRK–, the pooled HR estimate for OS was 1.51 (95% credible interval, 1.01 to 2.29). The patients analyzed had no previous or current exposure to TRK inhibitors. CONCLUSION: In patients not treated with TRK inhibitor therapies, those with NTRK+ solid tumors have a 50% increased risk of mortality within 10 years from diagnosis or the start of standard therapy compared with those with NTRK– status. Although this is the most robust estimate of the comparative survival rate to date, further studies are required to reduce uncertainty.