Overall survival indirect treatment comparison between brigatinib and alectinib for the treatment of front-line anaplastic lymphoma kinase-positive non-small cell lung cancer using data from ALEX and final results from ALTA-1L.

BACKGROUND: Second-generation anaplastic lymphoma kinase (ALK) gene targeted tyrosine kinase inhibitors (TKIs) alectinib and brigatinib have shown efficacy as front-line treatments for ALK-positive non-small cell lung cancer (NSCLC). No head-to-head data are currently available for brigatinib vs alectinib in the ALK-TKI-naive population. OBJECTIVE: To estimate the relative overall survival (OS) for brigatinib vs alectinib with indirect treatment comparisons (ITCs) using ALEX and ALTA-1L clinical trial data. METHODS: The latest aggregate data from the ALEX trial and final patient-level data from ALTA-1L were used. ITCs were conducted with/without treatment crossover adjustments to estimate relative OS. Bucher methods, anchored matching-adjusted indirect comparisons (MAICs) and unanchored MAICs were employed in ITCs without treatment crossover adjustments. An inverse probability of censoring weight Cox model, a marginal structure model and rank-preserving structural failure time models (with/without re-censoring) within an anchored MAIC were used in ITCs with treatment crossover adjustments. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. RESULTS: HRs for brigatinib vs alectinib for relative OS generated from ITCs without treatment crossover adjustments ranged from 0.90 (95% CI: 0.59-1.38) in the unanchored MAIC to 1.20 (95% CI: 0.69-2.11) using the Bucher method. Methods employing treatment switching adjustments estimated HRs for relative OS ranging from 0.74 (95% CI: 0.38-1.45) to 1.11 (95% CI: 0.63-1.94). Results from all ITCs did not indicate statistically different survival profiles. CONCLUSION: Regardless of ITC methodology, OS is comparable for brigatinib vs alectinib in patients with ALK+ NSCLC previously untreated with an ALK inhibitor

Indirect comparisons of brigatinib and alectinib for front-line ALK-positive non-small-cell lung cancer.

Aim: To conduct an indirect treatment comparison (ITC) of the relative efficacy of brigatinib and alectinib for progression-free survival in people with tyrosine kinase inhibitor (TKI)-naive ALK-positive non-small-cell lung cancer (NSCLC). Methods: Final aggregate and patient-level data from the ALTA-1L trial comparing brigatinib to crizotinib and published aggregate data from ALEX (comparing alectinib to crizotinib) were contrasted using Bucher ITC and matching-adjusted indirect comparisons (MAICs). Results: No statistically significant differences were identified between brigatinib and alectinib in reducing the risk of disease progression overall and in patients with baseline central nervous system metastases. Conclusion: Brigatinib appeared similar to alectinib in reducing risk of disease progression for people with TKI-naive ALK-positive NSCLC

Benefit of Prompt Vs Delayed Initiation of Triple Therapy Following an Exacerbation in Patients with COPD in Japan: A Retrospective Cohort Study

Alexandrosz Czira,1 Shoko Akiyama,2 Takeo Ishii,2 Robert P Wood,3 Lucinda J Camidge,3 Hannah Wallis,3 Thomas Jennison,3 Rosie AC Wild,3 Masao Yarita,2 Kenichi Hashimoto,2 Kieran J Rothnie,1 Afisi S Ismaila4,5 1Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, Middlesex, UK; 2Value Evidence and Outcomes, Japan Medical and Development, GSK, Tokyo, Japan; 3Real-World Evidence, Adelphi Real World, Bollington, UK; 4Value Evidence and Outcomes, R&D Global Medical, GSK, Collegeville, PA, USA; 5Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Kieran J Rothnie, Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, Middlesex, TW8 9GS, UK, Tel +44 7920 369573, Email [email protected]: There is currently limited evidence for the optimal timing of triple therapy initiation in Japan, which is crucial for optimizing strategies for the effective treatment of chronic obstructive pulmonary disease (COPD). This study assessed the impact of prompt vs delayed initiation of triple therapy following a COPD exacerbation on clinical and economic outcomes in patients in Japan.Patients and Methods: Retrospective cohort study of patients in the Medical Data Vision Co., Ltd. database initiating triple therapy as single-inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol or budesonide/glycopyrronium/formoterol) or multiple-inhaler triple therapy within 180 days of a moderate-to-severe exacerbation (index). For the main analysis, patients were categorized as prompt or delayed initiators, initiating triple therapy within 0– 30 days or 31– 180 days of index, respectively. Inverse probability of treatment weighting based on propensity scores was used to adjust for measured confounders between prompt and delayed cohorts.Results: For the main analysis, 610 (60.3%) and 402 (39.7%) patients were prompt and delayed initiators, respectively. The rate of subsequent moderate-to-severe exacerbations following index exacerbation was numerically lower in prompt vs delayed initiators (weighted rate ratio 0.95, 95% confidence interval [CI]: 0.74– 1.21; P = 0.6603). Time-to-first subsequent moderate-to-severe exacerbation increased significantly in prompt vs delayed initiators (weighted hazard ratio 0.77, 95% CI: 0.64– 0.93; P = 0.0053). In patients indexed on a severe exacerbation, delayed initiation resulted in significantly higher 90-day all-cause readmissions vs prompt initiation (42.1% vs 30.6%; P = 0.0329 [weighted estimates]). Weighted healthcare resource utilization rates were numerically lower in prompt vs delayed initiators, and weighted direct costs (all cause and COPD-related) were significantly lower in prompt initiators.Conclusion: This real-world study demonstrated that earlier initiation of triple therapy resulted in several benefits in clinical outcomes for COPD and may also reduce the economic burden of COPD management in Japan.Plain Language Summary: Patients with chronic obstructive pulmonary disease (COPD) can experience flare-ups in their symptoms, known as exacerbations. If exacerbations continue despite patients taking either one or a combination of two respiratory medications, guidelines suggest that they should take a combination of three treatments, known as triple therapy. In Japan, the best timing for patients to start triple therapy following an exacerbation is currently unknown, therefore this study compared the impact on clinical and economic outcomes of patients starting triple therapy 0– 30 days (prompt initiators) or 31– 180 days (delayed initiators) after their first exacerbation. When looking at clinical outcomes for COPD, we found that prompt initiators had a significantly longer time period from starting triple therapy to experiencing their next moderate-to-severe exacerbation, and those who had an initial severe exacerbation had significantly fewer hospital readmissions during the 90 days that followed their initial exacerbation than delayed initiators. When looking at economic outcomes for COPD, we found that medical costs were significantly lower in prompt versus delayed initiators. Findings of this study suggest that starting triple therapy earlier following an exacerbation may lead to improved clinical outcomes for patients with COPD in Japan and can reduce the cost of managing this disease.Keywords: healthcare resource utilization, hospital readmissions, direct medical costs, inverse probability of treatment weighting, single inhaler triple therapy, multiple inhaler triple therap