Pembrolizumab 1st-Line in NSCLC Also Boosts Quality of Life

Liam Davenport

December 08, 2016

VIENNA — More good news about using the immunotherapy pembrolizumab (Keytruda, Merck & Co) in the first-line treatment of advanced non–small cell lung cancer (NSCLC). Not only does it improve survival, new data show that it also improves quality of life (QoL) in comparision with chemotherapy.

Pembrolizumab was associated with clinically meaningful improvements in health-related QoL scores as well as an increase in the time to deterioration of symptoms in comparison with standard chemotherapy, said lead author Julie R. Brahmer, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland.

She said these new QoL data, when "combined with the superior progression-free survival [PFS] and overall survival [OS], as well as manageable safety profile that's been presented previously," led her to suggest that "pembrolizumab may be a new standard of care in the first-line treatment of advanced non–small cell lung cancer in patients with PD-L1 [programmed cell death ligand 1] expression scores of at least 50%."

The current findings, which were presented here at the 17th World Conference on Lung Cancer (WCLC), come from a preplanned analysis of results from the landmark KEYNOTE-024 clinical trial, which has already shown a survival benefit, as reported recently by Medscape Medical News.

The main results from the KEYNOTE-24 study were presented recently at the 2016 European Society for Medical Oncology and were simultaneously published in the New England Journal of Medicine.

The study was conducted in 305 patients with advanced NSCLC who had not yet received treatment and whose lung cancer biopsy results showed no epidermal growth factor receptor or anaplastic lymphoma kinase mutations and high expression of PD-L1 (≥50% of tumor cells).

The patients were randomly allocated to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years or 4 to 6 cycles of platinum-doublet chemotherapy. Patients in the latter group were switched to pembrolizumab if they experienced disease progression.

In this patient population, pembrolizumab alone gave superior results to a platinum-containing doublet chemotherapy — median PFS was 10.3 vs 6 months (hazard ratio [HR], 0.50), respectively.

The secondary endpoint of OS was also significantly better with pembrolizumab. OS at 6 months was 80% vs 72% (HR, 0.60); at 1 year, OS was 70% vs 54%.

Study Details

Dr Brahmer noted that for the current, prespecified analysis, the team looked at changes in baseline to week 15 in EORTC QLQ-C30 global health status/QoL scores, as well as the time to deterioration in the EORTC QLQ-LC13 composite endpoint of cough, chest pain, and dyspnea.

For purposes of the composite endpoint, dyspnea was defined as a decrease in symptoms of ≥10 points from baseline, confirmed by a second adjacent decrease in symptoms of ≥10 points. The assessment instruments were completed by patients after the first three cycles and every 9 weeks thereafter until disease progression, discontinuation, or 30-day safety assessment.

Importantly, there was a high level of compliance with the assessments that was maintained during follow-up, with 96% of patients in the pembrolizumab group and 93% of patients in the chemotherapy group completing the EORTC QLQ-C30 at baseline; at week 15, 85% and 79% of patients, respectively, completed it.

On constrained longitudinal data analysis, there was an improvement in EORTC QLQ-C30 global health status scores between baseline and week 15 with pembrolizumab, at a mean change of +6.9.

Scores in the chemotherapy arm, on the other hand, decreased over the same period, at a mean change of -0.9. The difference in mean change in scores between pembrolizumab-treated and chemotherapy-treated patients, at 7.8, was found to be significant (P = .002).

Dr Brahmer argued that the difference in mean change in scores between the pembrolizumab and chemotherapy arms, although small, was "clinically meaningful."

She said: "Some people might argue that a 7-point difference might not be clinically significant, but when you have patients treated with disease such as non–small cell lung cancer, where you have a lot of symptoms, a smaller change may be clinically significant.

"This is supported by some publications that say at least a 4-point difference one could consider as clinically significant," she added.

Moreover, there was a significant improvement in the time to deterioration on the EORTC QLQ-LC13 composite endpoint, with pembrolizumab patients less likely than chemotherapy patients to experience a deterioration event, at 46 vs 58 events, (HR, 0.66; P = .029).

Dr Brahmer noted: "We think it's very important to point out this time to deterioration of symptoms. Patients treated with pembrolizumab had a longer time until their symptoms deteriorated compared to those patients treated with chemotherapy."

These findings were reflected in differences in changes on function and symptom subscales of the EORTC QLQ-C30 between pembrolizumab and chemotherapy treatment groups, with pembrolizumab associated with a number of improvements in scores, as opposed to the decreases seen with chemotherapy.

These differences were also seen in changes in EORTC QLQ-LC13 individual symptoms. However, it is noteworthy that none of the differences in individual symptom scores on either instrument between the two treatment groups reached significance.

Discussing the study after its presentation, Michael Boyer, MD, PhD, chief clinical officer and conjoint chair of medical oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia, commented that it was "well conducted" and that the "appropriate instruments and analysis" were used.

He said: "I think what these data are telling us is that drugs that are effective tend to improve quality of life, provided they do not have significant toxicities or problems that they create.

"And I think that this gives us confidence to use these agents in the first-line setting in the knowledge that, not only do they improve overall survival, they at least maintain quality of life and, in this case, in fact improve quality of life."

Dr Boyer added: "That is important, because it lets us know that our patients are benefiting from this improvement of quality of life, as well as from their duration of life."

The study was supported by Merck & Co, Inc. Dr Brahmer is a member of the advisory board member at Merck. Dr Boyer has received research funding and honoraria have been paid to his institution from several organizations, including Merck.

17th World Conference on Lung Cancer (WCLC). Abstract PL04a.01. Presented December 7, 2016.

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