The PACIFIC study is an ongoing international, multicentre, randomized controlled trial that compares durvalumab with placebo in unresectable stage III NSCLC patients who have not progressed after definite treatment with concurrent chemoradiation. Patients were randomly (2:1) assigned to receive either durvalumab (10 mg/kg iv) or placebo every 2 weeks up to 12 months, beginning 1-42 days after the completion of chemoradiotherapy. Given that the primary outcomes of the study had already been reached and previously reported (i.e. PFS and OS benefit in the durvalumab arm with similar safety compared to the placebo arm), the aim of this study was to evaluate one of the secondary endpoints of the trial, namely the comparison of patient-reported outcomes (PROs) between the two arms. For this purpose, PRO symptoms, functioning, and quality of life were assessed with validated questionnaires (EORTC-QLQ-C30 and QLQ-LC13) at baseline and then at certain time-points until disease progression. Changes (deterioration or improvement) of 10-point or greater from baseline to 12 months in key symptoms were considered clinically relevant.
More than 79% and 82% of patients in the durvalumab (n=476) and the placebo (n=237) arm respectively, completed questionnaires up to week 48. No clinically relevant changes were found from baseline to 12 months in cough (adjusted mean change 1.8 in the durvalumab arm vs 0.7 in the placebo arm), dyspnea (3.1 vs 1.4), chest pain (–3.1 vs –3.5), fatigue (–3.0 vs –5.2), appetite loss (–5.8 vs –7.0), physical functioning (0.1 vs 2.0), and quality of life (2.6 vs 1.8). The differences in changes from baseline to 12 months in cough (difference in adjusted mean changes 1.1), dyspnea (1.6), chest pain (0.4), fatigue (2.2), appetite loss (1.2), physical functioning (–1.9), or quality of life (0.8) between the two arms were not clinically relevant as well. Finally, there were no clinically important differences in time to deterioration of the key PROs between the two arms.
Based on these results, the authors concluded that the clinical benefit of durvalumab can be achieved without affecting the PROs, allowing thus the replacement of observation by durvalumab treatment in the standard of care of patients with unresectable stage III NSCLC after the completion of concurrent chemoradiation.
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Although immunotherapy has been the standard of care of selected patients with metastatic (stage IV) NSCLC since a few years ago, the evidence about its effectiveness in patients with unresectable stage III (locally advanced) NSCLC was lacking. Until recently, the standard of care in such patients was concurrent chemoradiation followed by observation until disease progression. The PACIFIC study is the first large randomized controlled trial that demonstrated improved progression free survival (PFS) and overall survival (OS) with the use of durvalumab after the completion of chemoradiation in this population and brought immunotherapy in the standard of care of stage III NSCLC. However, despite the absence of significant differences in the frequency and severity of objectively recorded (e.g. investigator-reported) adverse events between the durvalumab and the placebo arm, there was no clue about the subjective experience (e.g. severity of symptoms, functioning and quality of life) of patients receiving the drug. The present study recorded the subjective experience of patients receiving durvalumab or placebo with the use of PROs and found no difference between the two study arms, strengthening thereby the replacement of observation by durvalumab in the standard of care of patients with unresectable stage III NSCLC.