PROs Were Consistent with the ITT Population Across PD-L1 Subgroups in Patients with Stage III NSCLC Receiving Durvalumab or Placebo

In PACIFIC, durvalumab significantly improved the primary endpoints progression-free survival (PFS) and overall survival (OS), with similar safety and without compromising patient reported outcomes (PROs), versus placebo in patients with locally advanced non-small cell lung cancer (NSCLC, ITT population). According to an analysis of PROs from the phase III PACIFIC trial by PD-L1 expression status, PRO outcomes by PD-L1 subgroups were generally consistent with those of the ITT population, suggesting that patients’ symptoms, functioning and global health status/quality of life (QoL) were maintained regardless of PD-L1 expression. Findings were presented at the 2019 European Lung Cancer Congress (ELCC), held 10 to 13 April in Geneva, Switzerland.

The PACIFIC study was conducted in patients with unresectable, stage III NSCLC who did not show disease progression following platinum-based concurrent chemoradiotherapy (cCRT). Significantly improved PFS and OS were demonstrated with durvalumab compared to placebo, thereby meeting the study primary endpoints. No detrimental effect was reported with durvalumab or placebo across PROs, prompting Marina C. Garassino, of the Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy, and colleagues to retrospectively investigate the impact of tumour PD-L1 expression on PROs to better understand the benefit/risk profile of durvalumab across all PD-L1 subgroups.

In PACIFIC, the patients received cCRT with ≥2 chemotherapy cycles; thereafter, patients were randomised 2:1 to durvalumab at 10 mg/kg or placebo i.v. every 2 weeks up to 12 months. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25%) and post-hoc (1%) cut-offs. The patients were analysed according to PD-L1 expression: TC 25% status (< 25%, ≥25%) and TC 1% status (< 1%, ≥1%), and PD-L1 unknown.

PROs were assessed using the EORTC Quality of Life Questionnaire 30 (QLQ-C30) and the lung cancer specific EORTC QLQ-LC13; the score range is 1 to 100 for both questionnaires. Higher scores on symptom scales represent greater symptom severity; higher scores on the global health status/QoL and functioning scales indicate better health status or function.

Changes from baseline were derived and summarised overall and by PD-L1 status, hazard ratios (HRs) for time to deterioration (TTD) were determined using a Cox proportional-hazards model, and odds ratios (ORs) for improvement rates were determined by logistic regression. 

Improvements in dysphagia and alopecia were observed in both study arms

Of the 713 randomised patients, 63% provided a tissue sample of sufficient quality and quantity to determine PD-L1 expression and 37% had unknown PD-L1 status.

The results of PRO analyses in the PD-L1 TC 25%, TC 1% and PD-L1 unknown subgroups for durvalumab compared to placebo were generally similar to those reported in the ITT population. Most PROs remained stable over time from baseline across all 5 PD-L1 subgroups, with no clinically meaningful differences observed between durvalumab and placebo, which was defined as a ≥10 points change from baseline.

However, similar to the ITT population, clinically meaningful improvements from baseline at week 48 were observed across most PD-L1 subgroups for dysphagia (mean changes of -8.1 to -20.9) and for alopecia (mean changes -15.5 to -26.9) with durvalumab and for dysphagia (mean changes -10.4 to -19.4) and alopecia (mean changes -15.8 to -31.3) with placebo. 

Results from pre-specified and post hoc TTD analyses of PROs by PD-L1 subgroup were also generally similar to those of the ITT population, with overlapping HRs and 95% confidence intervals.

Similarly, improvement rates according to PD-L1 subgroup indicated PROs were generally similar to those of the ITT population, with overlapping ORs and 95% confidence intervals observed.

Conclusions

Based upon these findings, the investigators were able to concludethat PRO results by PD-L1 subgroups were generally consistent with those of the ITT population, suggesting that patients’ symptoms, functioning and global health status/QoL were maintained regardless of PD-L1 expression, including among patients with PD-L1 TC <1%.

Reference

LBA2 – Garassino MC, Paz-Ares L, Hui R, et al. Patient-reported outcomes (PROs) with durvalumab by PD-L1 expression in unresectable, stage III NSCLC (PACIFIC).