Introduction: Non-cytotoxic therapy has changed the treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients and significantly improved outcomes. As survival outcomes continue to improve, quality of life (QOL) has become an important measure of success, and QOL analysis is increasingly being incorporated in clinical trial design. The objective of this systematic review was to assess the methodological quality of QOL analysis in NSCLC Randomized Clinical Trials (RCTs) involving biologic agents to treat NSCLC. Additionally, we assessed whether QOL measures included specific tools for neurological and cognitive measures for patients with central nervous system (CNS) involvement. Methods: A systematic literature search was performed using Medline, Embase, and Web of Science databases to identify NSCLC RCTs published between January 1 st ,1996 and January 10 th , 2020 reporting Quality of Life (QOL) measures. Only RCTs that both enrolled previously untreated patients with advanced NSCLC and had QOL analysis were included. Full-text analysis and data extraction was performed in duplicate. The CONSORT-PRO Extension checklist was used to evaluate the quality of included trials. Results: 4,439 abstracts were screened, of which only 96 RCTs met inclusion and exclusion criteria for analysis. 41,927 patients were enrolled in the included trials. The majority of trials included patients with treated brain metastases, but only 19 RCTs (8,444 patients) specified the incidence of CNS metastases at baseline with a median proportion of 11.57% (IQR 9.2 -23.2%). 33 trials involved biologic agents irrespective of tumor mutational status, and 17 studies only included patients that harbored a targetable mutation. The QOL assessment tools that were most commonly applied were EORTC-QLQ-LC13 (43 RCTs) and EORTC-QLQ-C30 (55 RCTs). The median number of verified CONSORT-PRO Extension criteria in the included trials was 3, and only in 10 trials were all 6 criteria well-documented. The least verified criteria were the following: report of statistical approaches for missing data (27 RCTs) and the discussion of limitations for QOL generalizability to clinical practice (41 RCTs). Only 13 RCTs performed subgroup analyses to specifically evaluate QOL. Better methodological quality of QOL reporting, defined by the number of fulfilled CONSORT-PRO Extension criteria, was observed in trials that included and specified the incidence of CNS metastases at baseline (p¼0.046) and in studies that only included patients with targetable mutations (p¼0.02) Conclusion: Considering the improving survival of lung cancer patients, more efforts should be pursued to analyze QOL in these patients. Further developing, standardizing, and implementing specific tools to analyze QOL is necessary to reflect the real-life experience of lung cancer patients in the era of personalized medicine.

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Objectives: We explored the temporal relationship between PRO changes, which are used to measure therapeutic impact, and subsequent clinical outcomes in mCRPC. MethOds: COU-AA-301 was a multinational, double-blind, randomized phase 3 trial of abiraterone acetate plus prednisone compared with prednisone alone in mCRPC patients progressing after chemotherapy, with an Eastern Cooperative Oncology Group performance status of ≤ 2. Using data from COU-AA-301 (N = 1195) over the first 181 days of treatment, we explored relationships between changes in clinical time-to-event outcomes and PROs measuring fatigue, pain, physical well-being (PWB), functional well-being (FWB), and prostate cancer-specific signs and symptoms. Cox regression models were developed to assess the relationship between each PRO (separately and for all simultaneously), and overall survival (OS) and radiographic progression-free survival as dependent variables, adjusting for important baseline clinical and PRO characteristics. Results: In each individual model, patients with PRO improvements had a reduced risk of death and radiographic progression compared with patients with worsening or stable PROs during follow-up. Hazard ratios (95% confidence intervals) for OS in patients with improved fatigue intensity, pain intensity, PWB, FWB, and prostate cancer-specific symptoms were 0.