KEYNOTE-024 Pembrolizumab Benefits Include HRQoL Outcomes

Patients derive a health-related quality of life advantage from first-line pembrolizumab for PD-L1-expressing metastatic non-small-cell lung cancer compared with chemotherapy

medwireNews: KEYNOTE-024 findings show that first-line pembrolizumab improves or maintains health-related quality of life (HRQoL), compared with platinum-based chemotherapy, in patients with stage IV non-small-cell lung cancer (NSCLC) positive for programmed cell death ligand 1 (PD-L1) expression.

The research, published in The Lancet Oncology, follows earlier results from the phase III trial demonstrating significantly longer progression-free survival and overall survival with the programmed cell death 1 (PD-1) inhibitor than with an investigators’ choice of platinum-doublet chemotherapy.

“Taken together, the superior survival, manageable safety profile, and favourable patient-reported outcome data obtained in the KEYNOTE-024 study suggest that pembrolizumab could be considered as a new standard of care for the first-line treatment of strongly PD-L1-expressing (tumour proportion score of 50% or more), advanced NSCLC”, the investigators believe.

Julie Brahmer, from Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland, USA, and team collated patient-reported outcome measures for 145 patients randomly assigned to receive pembrolizumab and 137 given chemotherapy.

The mean score at baseline in the EORTC Quality of Life Questionnaire (QLQ) Core 30 measure was 62.2 for the pembrolizumab-treated patients and 59.9 for the controls, and by week 15 the scores were 71.0 and 63.7, respectively. The corresponding change from baseline, calculated as the least-squares mean score, showed an improvement in the pembrolizumab arm but a decrease in the control arm (6.9 vs –0.9 points) and this difference reached statistical significance.

This was also reflected in the QLQ LC13 measure of lung cancer-associated symptoms and treatment-related symptoms. Pembrolizumab was associated with less deterioration in the composite endpoint of cough, chest pain and dyspnoea (31 vs 39%) over the 15 weeks, as well as a significantly longer time to deterioration, with median time not reached versus 5.0 months (hazard ratio=0.66).

Whilst acknowledging the relatively small number of patients who continued therapy for up to 33 weeks, the researchers note that the average change in QLQ-Core 30 global health status (GHS) and QoL scores showed more improvement in the pembrolizumab than chemotherapy arm through follow-up.

Julie Brahmer et al also found that disease progression in the first 15 weeks was associated with worsening GHS/QoL scores; for patients without progression, pembrolizumab offered greater score improvement than chemotherapy, while for progressing patients, pembrolizumab was associated with less score deterioration.

Massimo Di Maio, from the University of Turin in Italy, writes in an accompanying comment that the latest KEYNOTE 024 findings are “not surprising” and “reinforce the evidence supporting pembrolizumab as first-line treatment in advanced NSCLC with expression of PD-L1 on at least 50% of tumour cells.”

Believing that patient-reported outcomes and QoL results “allow a more complete definition of benefits and harms” for the treatments available to this population, however, he remarks: “A delay between the publication of primary endpoint results and QOL analysis is common for many trials, but the availability of QOL results along with the primary results would allow a timely evaluation of the benefit-to-risk ratio and of the value of the treatment.”

References

Brahmer JR, Rodríguez-Abreu D, Robinson AG, et al.  Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol; Advance online publication 9 November 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30690-3

Di Maio M. Quality of life: an important element of treatment value. Lancet Oncol; Advance online publication 9 November 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30697-6

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