Economic Impact of Next-Generation Sequencing Versus Single-Gene Testing to Detect Genomic Alterations in Metastatic Non-Small-Cell Lung Cancer Using a Decision Analytic Model.

PURPOSE: The aim of the current study was to assess the economic impact of using next-generation sequencing (NGS) versus single-gene testing strategies among patients with metastatic non-small-cell lung cancer (mNSCLC) from the perspective of the Centers for Medicare & Medicaid Services (CMS) and US commercial payers. METHODS: A decision analytic model considered patients who were newly diagnosed with mNSCLC who received programmed death ligand 1 and genomic alteration tests-EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1-using upfront NGS (all alterations tested simultaneously plus KRAS), sequential testing (sequence of single-gene tests), exclusionary testing (KRAS plus sequential testing), and hotspot panels (EGFR, ALK, ROS1, and BRAF tested simultaneously plus single-gene tests or NGS for MET, HER2, RET, and NTRK1). Model outcomes for each strategy were time-to-test results, the proportion of patients identified harboring alterations with or without US Food and Drug Administration-approved therapies, and total testing costs. A budget impact analysis assessed the economic effects of increasing the proportion of NGS-tested patients. RESULTS: In a hypothetical 1,000,000-member health plan, 2,066 Medicare-insured patients and 156 commercially insured patients were estimated to have mNSCLC and to be eligible for testing. Time-to-test results were 2.0 weeks for NGS and the hotspot panel, faster than exclusionary and sequential testing by 2.7 and 2.8 weeks, respectively. NGS was associated with cost savings for both CMS ($1,393,678; $1,530,869; and $2,140,795 less than exclusionary, sequential testing, and hotspot panels, respectively) and commercial payers ($3,809; $127,402; and $250,842 less than exclusionary, sequential testing, and hotspot panels, respectively). Increasing the proportion of NGS-tested patients translated into substantial cost savings for both CMS and commercial payers. CONCLUSION: Use of upfront NGS testing in patients with mNSCLC was associated with substantial cost savings and shorter time-to-test results for both CMS and commercial payers.

Can Ethiopia Finance the Continued Development of Its Primary Health Care System If External Resources Decline?

Ethiopia's recent improvements in health outcomes benefited from the large increase in development assistance for health received in recent years, most of which supported its primary care system. Increased domestic resource mobilization for health will be needed to sustain progress given recent and likely future declines in external support. We estimate a projection model of Ethiopian government domestic resource mobilization potential compared with future health care delivery costs in order to assess Ethiopia's ability to finance its planned primary health care system. For the period of Ethiopia's current five-year health sector plan (2016-2020), the projection model indicates that if real external resources remain at the levels of 2011, domestic resource mobilization may only provide half of the estimated funds needed. Including out-of-pocket spending currently captured as retained user fees, Ethiopia is more likely to successfully finance continued delivery of primary care. Over 20 years, 2016-2035, the future sustainability of primary care services without increasing contributions from households will depend largely on significant economic growth and more government funding for primary care. Our modeling suggests that Ethiopia can substantially support further development of primary care services, even in the face of declining external support. However, it is unlikely to achieve its goals solely through "business as usual." Ethiopia is already moving forward with timely adoption of sound strategies to maintain progress. External partners should support these trends to enable transition plans to greater domestic funding with minimal disruption to positive progress that has been and is being made.

Is time to progression associated with post-progression survival in previously treated metastatic non-small cell lung cancer with BRAF V600E mutation? A secondary analysis of phase II clinical trial data.

OBJECTIVE: Longer time to progression (TTP) is associated with prolonged post-progression survival (PPS) in anaplastic lymphoma kinase+non-small cell lung cancer (NSCLC). This study evaluated whether TTP is associated with PPS among previously treated patients with metastatic v-Raf murine sarcoma viral oncogene homolog B V600E NSCLC receiving dabrafenib as monotherapy or in combination with trametinib. DESIGN: Secondary analysis of phase II clinical trial data. SETTING: Patients who experienced disease progression treated with dabrafenib monotherapy or in combination with trametinib as second line or later in an open-label, non-randomised, phase II study. PRIMARY OUTCOME MEASURES: The primary outcome was the TTP-PPS association. PPS was assessed with Kaplan-Meier analysis among patients with shorter versus longer TTP (< or ≥6 months). The TTP-PPS association was quantified in the Cox models adjusting for clinical covariates. RESULTS: Of the 84 included patients who progressed on dabrafenib monotherapy (n=57) or combination therapy (n=27), 60 (71%) died during post-progression follow-up. Patients with TTP ≥6 months experienced significantly longer PPS compared with those with TTP <6 months (median PPS: 9.5 vs 2.7 months, log-rank p<0.001). Each 3 months of longer TTP was associated with a 32% lower hazard of death following progression (HR 0.68, 95% CI 0.52 to 0.88) in the multivariable Cox model. Similar associations were seen in each treatment arm. CONCLUSION: A longer TTP duration after treatment with dabrafenib monotherapy or combination therapy was associated with significantly longer PPS duration. TRIAL REGISTRATION NUMBER: NCT01336634; Post-results.

Comparative Efficacy of Treatments for Previously Treated Advanced or Metastatic Non-Small-Cell Lung Cancer: A Network Meta-Analysis.

INTRODUCTION: Due to the rarity of BRAF V600E mutation, no randomized study has compared the combination targeted therapy dabrafenib + trametinib with other second-line treatments for advanced or metastatic non-small-cell lung cancer (NSCLC). A network meta-analysis (NMA) was conducted to assess the comparative efficacy of treatments among patients with previously treated advanced or metastatic NSCLC. METHODS: Randomized trials of dabrafenib + trametinib, docetaxel, erlotinib, nintedanib + docetaxel, nivolumab, pemetrexed, pembrolizumab, and best supportive care as second-line or above treatments for advanced or metastatic NSCLC identified in a systematic literature review were included in the NMA. Overall response rates (ORRs) and disease control rates (DCRs) were compared using logit models; progression-free survival (PFS) and overall survival (OS) were compared using fractional polynomial hazards models. Dabrafenib + trametinib was linked into the evidence network through a matching-adjusted indirect comparison versus nivolumab. RESULTS: Ten trials met the inclusion criteria and were included in the NMA. Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with the highest odds of achieving overall response (12.2, 1.2, and 0.7 times higher, respectively, compared with docetaxel). Estimated DCR was higher for dabrafenib + trametinib, nintedanib + docetaxel, and pemetrexed compared with other treatments. Patients treated with dabrafenib + trametinib, nivolumab, and pembrolizumab had the lowest hazards of disease progression or death during follow-up (72, 61, and 29% lower hazard of progression at 6 months; 61, 48, and 46% lower hazard of death at 1 year, respectively, compared with docetaxel). CONCLUSION: Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with higher ORR and prolonged PFS and OS compared with chemotherapy in previously treated advanced or metastatic NSCLC. FUNDING: Novartis Pharmaceuticals Corporation.