P2.01-03 Quality of Life Outcomes for FDA-Approved Agents in Advanced Non-Small Cell Lung Cancer

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Symptom control and quality of life (QoL) improvement are among the most important goals of systemic therapy in advanced NSCLC, but they are not required for regulatory approval. We reviewed published QoL data for agents approved for use in advanced NSCLC by the United States Food and Drug Administration (FDA) and explore their potential uses in the era of precision medicine. Through systematic review, we identified 19 agents approved by the FDA for the treatment of advanced NSCLC between 1999 and 2017. Clinical trials associated with regulatory approval of these agents were identified. QoL results were abstracted from study publications, in addition to trial characteristics (phase, sponsor). 46 trials were identified supporting the FDA approval of the 19 agents. Of these, 33 (72%) were phase 3 randomized trials (including 3 cooperative group studies) and 13 (28%) were early phase (I/II) trials. QoL data were reported for 27 trials (59%), including all cooperative group trials. Another 5 (11%) measured QoL but results were not published. The remaining 13 (24%) trials did not measure QoL, 8/13 are phase III, 3/13 phase II and 2 phase I. In trials that reported QoL outcomes, better global QoL and cancer-related symptoms were identified in 17/33 (51%) and 18/33 (55%), respectively. Time to symptom deterioration was reported in 18 (55%) studies, with all but one showing benefit for the approved agent. The remaining studies reported no significant difference in QoL between study treatment arms. All studies reporting improved QoL parameters also reported improved response rates. In trials demonstrating OS and PFS improvement, 3/14 and 10/21 reported better QoL outcomes, respectively. ORR was higher in 26 trials, and it was associated with improvement in QoL in 12/26. Of 12 early phase trials leading to drug approval based on response rate and duration, 6 reported improved QoL outcomes. Three have not yet reported QoL data and 3 did not measure QoL. QoL is clearly associated with response rate but improved QoL or symptom control was only demonstrated in17/33 (51%) and 18/33 (55%) of studies supporting regulatory approval. QoL may be a clinically relevant endpoint for drug approval based on early phase trials of agents with high response rates and should be given further consideration by pharmaceutical sponsors and regulators in this era of precision medicine.