In patients with advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC), first-line afatinib significantly improved progression-free survival (PFS) and objective response vs. platinum-doublet chemotherapy in the phase III LUX-Lung 3 and LUX-Lung 6 trials, and significantly improved PFS, time to treatment failure and objective response vs. gefitinib in the phase IIb LUX-Lung 7 trial. We report post-hoc analyses of efficacy, safety and patient-reported outcomes (PROs) in afatinib longterm responders (LTRs) in these trials. Methods: Treatment-naïve patients with stage IIIB/IV EGFRm + NSCLC randomized to afatinib in LUX-Lung 3/ LUX-Lung 6/LUX-Lung 7 were included in the analysis. Patients treated with afatinib for ≥ 3 years were defined as LTRs. Results: In LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7, 24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinibtreated patients were LTRs. Baseline characteristics were similar to the study populations, except for the proportions of women (LUX-Lung 3/LUX-Lung 6 only; 92/78% vs. 64% overall) and Del19-positive patients (63-79% vs. 49-58% overall). Median treatment duration among LTRs was 50, 56 and 42 months, and median PFS was 49.5, 55.5, and 42.2 months in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7, respectively. Median overall survival could not be estimated. Frequency of afatinib dose reduction was consistent with the LUX-Lung 3/LUX

Objectives Assistive reproductive therapies can help those who have difficulty conceiving but different forms of assistive reproductive therapies are associated with different treatment characteristics. We undertook a large, multinational discrete choice experiment to understand patient preferences for assistive reproductive therapies. Methods We administered an online discrete choice experiment with persons who had experience with subfertility or assistive reproductive therapies in the USA, UK, the Nordic region (Denmark, Norway, Sweden, Finland), Spain, and China. Attributes encouraged trade-offs between effectiveness, risk of adverse effects, treatment (dis)comfort, (in)convenience, cost per cycle and shared decision making. We used multinomial logit and mixed-logit models to estimate preferences and attribute importance by country/region, and estimated willingness to pay for changes in attribute levels. Results A total of 7565 respondents participated. Mixed logit had a better fit than multinomial logit across all samples. Preferences moved in expected directions across all samples, but the relative importance of attributes differed between countries. Willingness to pay was greatest for improvements in effectiveness and a greater degree of shared decision making, and we observe a substantial 'option value' independent of treatment characteristics. Unexpectedly, preferences over cost were insignificant in the Chinese sample, limiting the use of willingness to pay in this sample. Conclusions Respondents balanced concerns for effectiveness with other considerations, including the cost and (dis)comfort of treatment, and the degree of shared decision making, but there is also substantial option value independent of treatment characteristics, demonstrating value of assistive reproductive therapies to individuals with experience of subfertility. We hypothesise that price insensitivity in the Chinese sample may reflect a degree of social desirability bias.

Highlights A quantitative survey was completed by infertile patients and partners to patients  Respondents waited an average of 3 years before receiving an infertility diagnosis  Motivational coherence within couples was a key driver to seek fertility treatment  Offerings of supportive services were positively correlated to treatment initiation  Perceived cost was the most frequently reported barrier to fertility treatment 2 Barriers and factors associated with significant delays to initial consultation and treatment for infertile patients and partners to infertile patients.

PurposeThe de facto standard method for valuing EQ-5D health states is the time trade-off (TTO), an iterative choice procedure. The TTO requires a starting point (SP), an initial offer of time in full health which is compared to a fixed offer of time in impaired health. From the SP, the time in full health is manipulated until preferential indifference. The SP is arbitrary, but may influence respondents, an effect known as anchoring bias. The aim of the study was to explore the potential anchoring effect and its magnitude in TTO experiments.MethodsA total of 1249 respondents valued 8 EQ-5D health states in a Web study. We used the lead time TTO (LT-TTO) which allows eliciting negative and positive values with a uniform method. Respondents were randomized to 11 different SPs. Anchoring bias was assessed using OLS regression with SP as the independent variable. In a secondary experiment, we compared two different SPs in the UK EQ-5D valuation study TTO protocol.ResultsA 1-year increase in the SP, corresponding to an increase in TTO value of 0.1, resulted in 0.02 higher recorded LT-TTO value. SP had little impact on the relative distance and ordering of the eight health states. Results were similar to the secondary experiment.ConclusionThe anchoring effect may bias TTO values. In this Web-based valuation study, the observed anchoring effect was substantial. Further studies are needed to determine whether the effect is present in face-to-face experiments.

Background The therapeutic landscape for non-small-cell lung cancer (NSCLC) patients that have common epidermal growth factor receptor (EGFR) mutations has changed radically in the last decade. The availability of these treatment options has an economic impact, therefore a budget impact analysis was performed. Methods A budget impact analysis was conducted from a Dutch healthcare perspective over a 5-year time horizon in EGFR-mutant NSCLC patients receiving first-line afatinib (Gilotrif ®) versus first-line osimertinib (Tagrisso ®), followed by subsequent treatments. A decision analysis model was constructed in Excel. Scenario analyses and one-way sensitivity analysis were used to test the models' robustness. Results Sequential treatment with afatinib versus first-line treatment with osimertinib showed mean total time on treatment (ToT) of 29.1 months versus 24.7 months, quality-adjusted life months (QALMs) of 20.2 versus 17.4 with mean cost of €108,166 per patient versus €143,251 per patient, respectively. The 5-year total budget impact was €110.4 million for the afatinib sequence versus €158.6 million for the osimertinib sequence, leading to total incremental cost savings of €48.15 million. Conclusions First-line afatinib treatment in patients with EGFR-mutant NSCLC had a lower financial impact on the Dutch healthcare budget with a higher mean ToT and QALM compared to osimertinib sequential treatment.