Patient-centered outcomes in non-small-cell lung cancer: a real-world perspective.

Aims: To assess non-small-cell lung cancer (NSCLC) patient-centered outcomes in the real world. Methods: This is a prospective study of NSCLC patients treated at a private cancer care institution in Brazil between 2014 and 2019. Results: The report comprises 337 patients. Advanced stage was associated with higher symptom burden - fatigue (p = 0.03), pain (p < 0.001) and arm pain (p = 0.022) - and worse global, social and physical functioning (all p < 0.001). In the first 2 years, most factors evolved to either improvement or stability: cough (p = 0.02), pain (p = 0.002), global functioning (p < 0.001) and emotional functioning (p < 0.001). Staging (p < 0.001), fatigue (p = 0.001) and gender (p = 0.004) were independently associated with overall survival. Conclusions: Our results demonstrate the feasibility of conducting real-world prospective analysis of patient-centered outcomes.

Lay abstract This study looked at patient-centered outcomes in lung cancer in a real-world setting. Standardized quality-of-life questionnaires were used to actively measure patients' perception of their functional well-being and health in a clinical setting. Three hundred thirty-seven patients were enrolled in a private cancer center in Brazil between 2014 and 2019. We demonstrated that patients diagnosed at advanced stages presented with more symptoms and lower capacity to perform daily activities. However, symptoms and functioning tended to improve during treatment. Our results show that it is possible to put patients at the heart of cancer care and use their experience to guide clinical approach.

Evidence Strength of Pharmaceutical Industry-Funded Clinical Trials in Metastatic NSCLC: A Comparison With Other Sources of Funding.

INTRODUCTION: Clinical trials are expensive and often require funding from the pharmaceutical industry (PI). We aimed to compare studies funded by the PI with those funded by other sources in terms of costs, reported results, and strength of evidence. METHODS: We searched PubMed for clinical trial reports on metastatic NSCLC published between 2012 and 2017. We divided all the studies into two groups: studies funded by the PI and those funded by other sources. The primary end point was to compare the evidence strength of each group. The secondary end points were to compare the number of patients included, the number and costs of innovative drugs studied, whether there was preferential reporting of positive results in the experimental arm, and the risk of bias. RESULTS: We found 3004 studies, and of these, we analyzed 477 studies (275 sponsored by the PI and 202 funded by other sources). A total of 85,328 patients overall were included (64,434 in studies sponsored by the PI and 20,894 in studies with other funding sources; p < 0.001). The studies funded by the PI had stronger evidence (p < 0.001), evaluated more innovative therapies (72% versus 36%; p < 0.001), and resulted in a higher proportion of open-access manuscripts (63% versus 47%; p < 0.001). There was no considerable difference regarding the reporting of experimental arm superiority or the risk of bias between the two groups. CONCLUSIONS: Compared with studies from other sources of funding, those funded by the PI in the lung cancer field collected stronger evidence, assessed more expensive and innovative therapies, and seemed to equally emphasize positive and negative results.

Cost-Effectiveness of Cabozantinib in the Second-Line Treatment of Advanced Hepatocellular Carcinoma.

BACKGROUND: Treatment options are limited for patients with advanced hepatocellular carcinoma (HCC) that progresses after treatment with sorafenib. Cabozantinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, recently showed improved overall survival (OS) compared with placebo in sorafenib-pretreated patients with advanced HCC in the CELESTIAL trial. This study assessed the cost-effectiveness of cabozantinib for second-line treatment of patients with advanced HCC from a US healthcare system perspective. PATIENTS AND METHODS: Cost and utility data were extracted from the CELESTIAL trial and used to determine the cost-effectiveness of cabozantinib compared with placebo plus best supportive care. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained by using cabozantinib compared with placebo plus best supportive care in sorafenib-pretreated HCC. RESULTS: In the base-case analysis using data from the CELESTIAL trial, the incremental QALY and ICER were 0.067 and $1,040,675 for cabozantinib compared with placebo and best supportive care. OS reported in the CELESTIAL trial (hazard ratio, 0.76; 95% CI, 0.63-0.92) had the strongest association with the ICER. In one-way sensitivity analyses, there were no scenarios in which cabozantinib was cost-effective. In a cost-threshold analysis, cabozantinib would have to be priced at least $50 per pill to be cost-effective considering a willingness to pay of $100,000 per QALY. Although the CELESTIAL trial demonstrated that cabozantinib improves OS compared with placebo in patients with HCC that progresses after treatment with sorafenib, our analysis shows that cabozantinib is not a cost-effective therapy in this scenario. CONCLUSIONS: At current costs, cabozantinib is not cost-effective for second-line therapy of HCC in the United States.

Cost-effectiveness of Osimertinib in the First-Line Treatment of Patients With EGFR-Mutated Advanced Non-Small Cell Lung Cancer.

Importance: The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients. Objective: The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC. Design, Setting, and Participants: For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first- and second-generation EGFR-TKIs over a 10-year time horizon. All direct costs were based on US and Brazilian payer perspectives. Main Outcomes and Measures: The main outcome of this study was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained by using osimertinib compared with first- or second-generation EGFR-TKIs in previously untreated EGFR-mutated NSCLC. Results: In the base case using the data as reported in the FLAURA trial, the incremental QALY for osimertinib was 0.594 compared with the first- and second-generation EGFR-TKIs. In the United States, the osimertinib ICERs were $226 527 vs erlotinib, $231 123 vs gefitinib, and $219 874 vs afatinib. In Brazil, the ICERs were $162 329, $180 804, and $175 432, respectively. The overall survival (95% CI) reported in the FLAURA trial (hazard ratio, 0.63; 95% CI, 0.45-0.88) had the strongest association with the ICER (ranging from $84 342 to $859 771). Osimertinib price adjustments to the FLAURA trial data improved cost-effectiveness. For example, a discount of 10% on osimertinib acquisition cost was associated with a 20% decreased ICER compared with the base case ICER, and a discount of 20% on osimertinib acquisition cost was associated with a 40% decreased ICER compared with the base case ICER. Conclusions and Relevance: At current costs, by World Health Organization cost-effectiveness threshold criteria, osimertinib is not cost-effective for first-line therapy of EGFR-mutated NSCLC in either the United States or Brazil.

PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data.

AIM: The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. METHODS: We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. RESULTS: 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). CONCLUSION: PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung cancer and the role of PD-L1 as a predictive biomarker.

BACKGROUND: Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. METHODS: To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. RESULTS: Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%. For those with PD-L1 expression <1%, nivolumab showed a trend for improved survival compared with docetaxel. CONCLUSIONS: The available data reinforce nivolumab activity against NSCLC in first-line or subsequent lines. Although PD-L1 expression is related to greater response, PD-L1 negative patients had also some benefit.

EGFR and EML4-ALK Updated Therapies in Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer is the leading cancer-related cause of death. OBJECTIVE: We review the latest therapies for NSCLC with EGFR and ELM4-ALK mutations as well as the most relevant studies and promising patents. METHOD: A literature search of PubMed database was carried out to identify recent Clinical Trials using EGFR therapies and novel patents involving diagnosis and therapies on NSCLC. We conducted a search to find new therapy strategies, new biomarkers, and selected five patents we find relevant. RESULTS: Over the last few years, identification of cancer harboring epidermal growth factor receptor mutations (EGFR) or chromosomal rearrangements of anaplastic lymphoma kinase (ALK) led to new ways in classifying and treating NSCLC. On the other hand, acquired resistance are a constantly challenge in the management of patients with these mutations and new drugs options are in development to improve and amplify treatment strategies. CONCLUSIONS: Currently, EGFR TKIs (e.g.: erlotinib, gefitinib, osimertinib) and ALK inhibitors (crizotinib, ceritinib, alectinib) provided a new face for advanced NSCLC outcomes. To understand the disease molecular profile is mandatory to define the best approach for each patient.

The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis.

BACKGROUND: Tumor programmed death ligand one (PD-L1) expression has been studied in several trials in non-small-cell lung cancer. METHODS: We assessed the potential role of PD-L1 expression according to Cochrane Collaboration's Guidelines. RESULTS: 13 studies with 1979 patients were included. Among 915 PD-L1 negative patients this rate was 13% (RR 2.08; 95% CI: 1.49-2.91; p < 0.01). The response rate has increased concurrent to the PD-L1 expression (Pearson's correlation, r = 0.43). PD-L1 expression was also related to better 24-weeks progression-free rate (RR 0.79; 95% CI: 0.71-0.89) and a trend toward better 1-year overall survival rate (RR 0.96; 95% CI: 0.87-1.06). CONCLUSION: Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment.