Scott J. Antonia, MD
Durvalumab treatment over 12 months had no negative effect on key symptoms of lung cancer, physical function, global health status, or quality of life (QoL) in patients with locally advanced, unresectable stage III non–small cell lung cancer (NSCLC) who have not progressed following concurrent chemoradiotherapy.
The findings come from patient-reported outcomes (PROs) compiled during the phase III PACIFIC trial (NCT02125461) that were presented at the 2018 European Lung Cancer Congress (ELCC). Global health status was similar between the durvalumab and placebo groups (HR, 0.99), as was physical functioning (HR, 1.08), and role functioning (HR, 1.00).
The time to deterioration was longer with durvalumab than with placebo for emotional functioning (HR, 0.77), nausea/vomiting (HR, 0.72), insomnia (HR, 0.75), hemoptysis (HR, 0.70), chest pain (HR, 0.74), and arm/shoulder pain (HR, 0.74).
No statistically significant differences between treatment groups in adjusted mean changes from baseline over 12 months were observed using a mixed model for repeated measures analysis of the prespecified symptoms of dyspnea (HR, 0.94), cough (HR, 0.92), chest pain (HR, 0.92), fatigue (HR, 0.90), and appetite loss (HR, 1.08), which all slightly favored durvalumab, except appetite loss.
Lead investigator Scott Antonia MD, PhD, of the H. Lee Moffitt Cancer Center and Research Institute, presented updated QoL results at the 2018 ELCC from a prespecified posthoc analysis of data from the phase III PACIFIC trial of durvalumab versus placebo. The analysis included PRO data adjusted for transient symptom changes by requiring 2 consecutive recordings of symptom deterioration.
“Transient changes in symptoms, such as temporary symptoms due to treatment side effects or comorbidities, may introduce bias and confound an analysis of symptom change associated with disease progression, so we required deterioration to be confirmed at the next consecutive time points,” said Antonia.
In the PACIFIC trial, which took place at 235 centers in 26 countries, 473 patients were randomized to durvalumab and 236 were randomized to placebo. Patients had nonresectable, locally advanced NSCLC and did not have disease progression following ≥2 cycles of platinum-based concurrent chemoradiotherapy. Patients received treatment ranging from 1 to 42 days after chemoradiotherapy. Durvalumab was administered at 10 mg/kg IV every 2 weeks for up to 12 months or until disease progression.
Durvalumab significantly improved progression-free survival (PFS) with a median PFS of 16.8 months with durvalumab compared to 5.6 months with placebo (HR, 0.52; 95% CI, 0.42-0.65; P
<.001). The safety profile in PACIFIC indicated that durvalumab was well tolerated.
“Along with improving efficacy outcomes, such as progression-free survival after concurrent chemoradiotherapy in locally advanced, unresectable NSCLC, it is critical that new therapies are well tolerated in the curative intent setting,” said Antonia.
PROs using EORTC QLQ-C30 v3 and QLQ-LC13 were assessed at baseline and weeks 4 and 8 and every 8 weeks thereafter until week 48. The last assessment for patients who discontinued treatment due to disease progression was done on day 30 after the final dose. Time to deterioration was defined as time from randomization until the first clinically relevant deterioration, with a ≥10-point change considered as clinically relevant.
Compliance with completion of the questionnaires was more than 80% in both treatment arms up to week 48.
“It should be kept in mind that this comparison is not between two drugs but between durvalumab and placebo, which is, in effect, no treatment with no adverse effects,” Antonia noted. “Alongside the positive efficacy and safety data from PACIFIC, these findings further support the clinical benefit of durvalumab in this setting,” said Antonia.
In February 2018, the FDA approved durvalumab for the treatment of patients with locally advanced, unresectable stage III NSCLC who have not progressed following chemoradiotherapy.
Hui R, Özgüroğlu M, Villegas A, et al. Time to deterioration of symptoms with durvalumab in stage III, locally advanced, unresectable NSCLC: post-hoc analysis of PACIFIC patient-reported outcomes. Presented at: the 2018 European Lung Cancer Conference; April 11-14; Geneva, Switzerland. Abstract 233O.<<< 2018 European Lung Cancer Congress