As reported in The Lancet Oncology by Hui et al, no clinically important differences in patient-reported outcomes were observed among patients receiving durvalumab vs placebo after chemoradiation for stage III unresectable non–small cell lung cancer (NSCLC) in the phase III PACIFIC trial.
The PACIFIC trial has shown significantly improved progression-free and overall survival with durvalumab vs placebo in patients with unresectable stage III NSCLC with no disease progression after at least two cycles of platinum-based chemoradiotherapy.
Study Details
In the double-blind trial, 476 patients were assigned to receive durvalumab at 10 mg/kg and 237 were assigned to receive placebo every 2 weeks for up to 12 months following chemoradiotherapy. Patient-reported outcomes were assessed by the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-Lung Cancer 13 (QLQ-LC13) at randomization, at weeks 4 and 8, every 8 weeks until week 48, and then every 12 weeks until disease progression.
Higher scores on symptom scales and items represent greater symptom severity and higher scores on global health status/quality of life and functioning scales indicate better status/function. Changes from baseline to 12-month follow-up in key symptoms were analyzed using a mixed model for repeated measures (MMRM) and time-to-event analyses. Clinically relevant changes were defined as 10-point or greater changes from baseline.
Key Findings
Median follow-up was 25.2 months. More than 79% of patients treated with durvalumab and more than 82% of patients treated with placebo completed questionnaires up to week 48. The investigators reported:
- Between baseline and 12 months, key patient-reported outcomes remained stable and showed no clinically relevant changes from baseline. MMRM-adjusted mean changes for durvalumab vs placebo patients were 1.8 vs 0.7 for cough, 3.1 vs 1.4 for dyspnea, −3.1 vs −3.5 for chest pain, −3.0 vs −5.2 for fatigue, −5.8 vs −7.0 for appetite loss, 0.1 vs 2.0 for physical functioning, and 2.6 vs 1.8 for global health status/quality of life.
- No clinically relevant between-group differences in adjusted mean changes from baseline to 12 months were observed for cough (1.1), dyspnea (1.6), chest pain (0.4), fatigue (2.2), appetite loss (1.2), physical functioning (−1.9), or global health status/quality of life (0.8).
- No clinically relevant between-group differences were observed in time to deterioration for most symptoms, functioning terms, or global health status/quality of life; time to deterioration of other pain (pain other than in chest, arms, or shoulders) was longer in patients treated with durvalumab.
The investigators concluded: “Our findings suggest that a clinical benefit with durvalumab can be attained without compromising patient-reported outcomes. This result is of note because the previous standard of care was observation alone, with no presumed detriment to patient-reported outcomes.”
Rina Hui, PhD, of Westmead Hospital and University of Sydney, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
