Dirk Schadendorf, MD
There were few differences in quality of life (QoL), global health, and symptom burden between patients with melanoma who were treated with nivolumab (Opdivo) plus ipilimumab (Yervoy) or either agent alone, according to a recent analysis of patient-reported outcomes from the phase III CheckMate-067 trial.
After one year of follow-up, patients in the nivolumab plus ipilimumab arm of the CheckMate-067 trial experienced no clinically meaningful change in health-related QoL—even though they showed significant improvements in survival. Additionally, patients treated with nivolumab alone or ipilimumab alone showed no significant changes in QoL compared to baseline, said Dirk Schadendorf, MD, during a presentation at the 2015 Society for Melanoma Research Congress.
“The nivolumab plus ipilimumab treatment arm had the highest frequency of adverse events, but these adverse events did not seem to affect patient-reported QoL outcomes,” said Schadendorf, director of the department of dermatology, the West German Cancer Center at the University Hospital in Essen, Germany.
In the CheckMate-067 study, 945 patients with advanced melanoma were treated with nivolumab alone, ipilimumab alone, or the combination of nivolumab plus ipilimumab. Results revealed that patients in the combination arm showed improved progression-free survival (PFS). The median PFS with the combination was 11.5 versus 6.9 months with nivolumab alone and 2.9 months with ipilimumab alone.
Adverse events (AEs) were more frequent with the combination treatment, with 55% of patients in nivolumab plus ipilimumab having grade 3/4 AEs versus 16.3% with nivolumab alone and 27.3% with ipilimumab. Additionally, over 29% of patients in the combination arm experienced a treatment-related AE leading to treatment discontinuation.
Despite the higher incidence, AEs in the CheckMate-067 study were short-lived. The median time for resolution of grade 3/4 AEs was 1.7 to 4.2 weeks, Schadendorf said.
To assess patient-reported QoL, researchers used the EORTC QLQ30 cancer specific QoL questionnaire and the EQ-5D scale, which assesses health status and global health. The EQ-5D includes a visual analog scale (VAS) in which patient rate their health status on a scale from 0 to 100, as well as a descriptive system which asks participants to rate 5 dimensions of their health in terms of self-care, mobility, usual activities, pain/discomfort and anxiety/depression.
Schadendorf noted that patient characteristics were well balanced among the treatment arms at baseline, suggesting that it is unlikely that pre-existing patient health outcomes affected the results.
Reductions were seen in EORTC scores across all arms (P
≤.01); however, these findings were not deemed to be clinically meaningful (≤10 points change). At week 5, there was reduction of 2.7, 4.3, and 3.1 points for nivolumab alone, nivolumab plus ipilimumab, and ipilimumab alone, respectively. Scores returned to baseline levels by week 25 in the nivolumab alone arm and by week 31 in the combination and ipilimumab alone arms.
The EQ-5D scores improved at week 13 with nivolumab alone (P
= .042), which persisted throughout the trial. However, in the ipilimumab containing arms, EQ-5D scores initially worsened before returning to baseline by week 13 for the combination and by week 19 for ipilimumab alone. VAS scores were stable for the nivolumab-containing arms and worsened with ipilimumab until week 23.
“Even among patients who suffered severe toxicities such as colitis, treatment did not appear to have a significant effect on quality of life,” Schadendorf said. “Do the results in this study indicate that patients don’t care about toxicity when they receive a large survival benefit, or is it that QoL wasn’t affected because the toxicities were short-lived?” he asked.
One shortcoming of the analysis was that patients who discontinued treatment were not included in QoL assessment, Schadendorf said. To account for this, data are being analyzed that include patients who progressed or discontinued. Additionally, patients will continue to be followed in the study to assess whether the tumor control benefits observed in CheckMate-067 will affect long-term patient QoL outcomes, he said.
“One possible explanation for our findings in this study could be that the tools we have now—utilized in our analysis—are not very useful for assessing QoL in patients treated with newer immunotherapy agents,” Schadendorf said. “Yet these are the only instruments we have that are validated, and it could take years to obtain new and better validated tools.”
Schadendorf D, Long G, Larkin J, et al. Patient reported outcomes (PROs) from a phase 3 study of Nivolumab (NIVO) alone or combined with Ipilimumab (IPI) versus IPI in patients with advanced melanoma. CheckMate 067. Presented at the Society for Melanoma Research 2015 International Congress; November 18-21, 2015; San Francisco, CA.
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