HRQoL Stable During Ipilimumab Therapy For High-Risk Melanoma

Patients given adjuvant ipilimumab for high-risk stage III melanoma do not experience a significant global decrease in health-related quality of life compared with placebo-treated controls

medwireNews: Ipilimumab toxicity does not translate into a significant impact on global health-related quality of life (HRQoL), suggests a secondary analysis of the EORTC 18071 trial of patients with high-risk stage III cutaneous melanoma.

The study investigators previously reported results for the phase III trial indicating that the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor significantly extended recurrence-free survival compared with placebo, but that a quarter of patients experienced grade 3–4 adverse events.

However, they now report in The Lancet Oncology that, although 39% of patients discontinued ipilimumab during the induction phase of the trial because of toxicity, participants did not experience a clinically relevant decrease in global HRQoL, defined as a 10-point or greater decrease on the EORTC QLQ-C30 instrument score.

Michael Brundage and Timothy Hanna, from Queen’s University in Kingston, Ontario, Canada, write in a linked comment that “[t]he contrast between the investigator-reported toxicity and the global HRQoL results seems counterintuitive and might raise concern regarding the validity of the HRQoL findings.”

They caution that there was an imbalance in data available for patients given ipilimumab and placebo and that patients with poorer HRQoL might be less likely to complete the questionnaire.

Nevertheless, they commend the use of a “well-validated instrument” and say that it is “plausible” that severe symptoms might have a “modest impact” on global HRQoL “since these symptoms can be effectively managed and thus [are] transient.”

Overall, 94% of patients completed the HRQoL at baseline, 75% at week 24 and 51% at week 108, report Corneel Coens, from EORTC Headquarters in Brussels, Belgium, and co-authors.

At baseline, the 475 patients given ipilimumab had a mean global HRQoL score of 72.96 versus 77.32 for the 476 placebo-treated patients, with corresponding scores of 72.32 and 76.48 at the end of four induction doses given on days 1, 22, 43 and 64. Although scores significantly differed between the treatment arms at both times, there was not a clinically relevant difference, the researchers explain.

The biggest differences in the mean global health score between the ipilimumab and placebo groups were at weeks 7 (71.55 vs 76.97) and 10 (69.52 vs 77.41) and were not clinically relevant.

At week 10, however, patients given ipilimumab experienced clinically relevant deteriorations in diarrhoea, insomnia and fatigue compared with controls, with a greater than 10-point difference noted for diarrhoea (7.67 vs 18.17) and insomnia (15.17 vs 25.60).

Corneel Coens et al admit that some researchers have advocated for a lower threshold for clinically relevant change, such as a 4-point difference in HRQoL score that would have resulted in several clinically relevant global score decreases in the current study.

“Therefore, the observed deteriorations in the ipilimumab group cannot be dismissed as trivial and should be interpreted with care”, they say.

Nevertheless, the investigators conclude: “This study shows that ipilimumab treatment can result in an improvement in recurrence-free survival compared with that after placebo treatment, with little impairment in HRQoL measured with the QLQ-C30 questionnaire, despite severe side-effects.” 

References

Coens C, Suciu S, Chiarion-Sileni V, et al. Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial. Lancet Oncol; Advance online publication 2 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30015-3

Brundage M, Hanna T. Adjuvant ipilimumab for stage III melanoma: the patient voice. Lancet Oncol; Advance online publication 2 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30003-7

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