OBJECTIVES: The objective of this study was to assess current evidence on epidemiological, clinical and humanistic burden among ALK+NSCLC patients receiving approved first-line ALK inhibitors.

METHODS: An SLR following PRISMA guidelines with scope defined in terms of PICOS criteria (Population, Intervention, Comparators, Outcomes and Study Design) was conducted. EMBASE, MEDLINE and Cochrane databases (1/2008−9/2018) and conference proceedings (2016−2018) were searched, along with ClinicalTrials.gov and health technology assessments. Prospective and retrospective studies as well as studies reporting quality of life (QOL) or utility data were included. Weighted averages of patient characteristics and outcomes were determined among studies investigating approved first-line ALK inhibitors (crizotinib, ceritinib, alectinib) in ALK+NSCLC.

RESULTS: We identified 239 eligible records: 215 real-world evidence (RWE) and 25 QOL. Based on 140 studies reporting patients’ characteristics, average age was 56.4 years, 49.4% were male and 36.2% were smokers. Clinical outcomes with first-line ALK inhibitors were reported in 97 studies (89 retrospective, 8 prospective) with samples ranging from 6−428 patients. 32 studies reported brain metastases at baseline (7.6%−55.0%). All studies included crizotinib and 9.3% of studies included alectinib and/or ceritinib. On average, median overall survival was 27.8 months, with 70.6% and 55.2% of patients surviving at 12 and 24 months, respectively. Median progression-free survival (mPFS) was 10.1 months and overall response rate was 60.9% with first-line ALK inhibitors. EORTC QLQ-C30 or QLQ-LC13 were the main QOL instruments. QOL diminished with disease progression, utility values ranged 0.6−0.8 in first-line treated stable patients versus 0.5−0.6 in those with progression.

CONCLUSIONS: This SLR suggests that currently real-world used first-line ALK inhibitors showed poor survival rates and short PFS among ALK+NSCLC patients. Disease progression was associated with reduced patient QoL. These results indicate a need for more effective first-line treatments for ALK+NSCLC.