BACKGROUND: Recent randomized clinical trials (RCTs) have explored survival benefits of second-line treatments (2LTs) in patients who have rapidly progressed and/or are refractory to first-line treatment, and these trials have determined an existing unmet need for these patients with aggressive non-small cell lung cancer (NSCLC). However, specific characterization of aggressive NSCLC is lacking, thus a systematic literature review was conducted to explore the definitions of aggressive NSCLC.
METHODS: We systematically searched Medline, Embase, BioSciences Information Service, the Cochrane Library, and abstracts from scientific meetings (through October 2017) to identify RCTs reporting the efficacy and/or safety of select 2LTs in patients with advanced NSCLC who have characteristics associated with aggressive disease(AD). Six potential overarching categorizations of these characteristics (based on expert clinical opinion) were explored: (1) refractory and/or progressive disease as best response to prior treatment, (2) rapid progression, (3) short duration on previous treatment, (4) high tumor burden or size, (5) short duration since start of last treatment, and (6) high symptom burden.
RESULTS: The 14 identified studies had one or more subgroups within five of the six categorizations (11, 2, 1, 2, and 4 studies presented subgroups within categories 1-5, respectively). No RCTs presenting a subgroup of patients for category 6 were identified. Within each category, the identified subgroup definitions varied (15, 4, 3, 2, and 7 different definitions within categories 1-5, respectively). Reporting of whether a subgroup was prespecified or not was limited and often unclear; 6 studies indicated that subgroup analyses of patients with AD characteristics were preplanned. Moreover, baseline characteristics for the subgroup of patients with AD were often not reported.
CONCLUSION: Definitions of AD varied, both across the identified studies of 2LTs and within the predetermined categorizations, with refractory being the most frequent followed by short duration since start of last treatment. With the emerging clinical importance of AD, more standard use of these definitions within RCTs may allow for greater comparison across 2LTs and will enable indirect treatment comparisons of the results. As with any subgroup, clarity on preplanned versus post hoc analysis is important for interpretation and should be specified. Additional studies powered to assess treatment benefits in advanced NSCLC patients with AD are needed.
