Advanced melanoma patients successfully treated with a combination of nivolumab and ipilimumab may endure severe side effects, but they do not suffer any clinically meaningful changes in health-related quality of life.
Advanced melanoma patients successfully treated with a combination of nivolumab and ipilimumab may endure severe side effects, but they do not suffer any clinically meaningful changes in health-related quality of life (QoL), according to a new study presented at the Society for Melanoma Research 2015 International Congress, held November 18–21 in San Francisco.
Patient-reported outcomes (PROs), such as symptoms, health-related QoL, and patient-perceived health status, play an important role in clinical trials. “PROs supplement clinical outcomes and provide a holistic understanding of patient experience and treatment effectiveness, and help inform therapeutic choices, disease management practices, reimbursement decisions, and health policy,” said Dirk Schadendorf, MD, director of the department of dermatology at the University Hospital Essen in Essen, Germany.
Several validated cancer-specific PRO instruments have been used in melanoma, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of Cancer Therapy-melanoma subscale.
“Immuno-oncology agents show promise in prolonging survival. It is important to evaluate the quality of extended life of patients during and after treatment. In addition to traditional outcomes, PROs offer insights into the quality of long-term survival,” Dr. Schadendorf said.
The phase III CheckMate 067 trial, which included 945 untreated melanoma patients, found that nivolumab alone and in combination with ipilimumab significantly improved progression-free survival (PFS) and the overall response rate (ORR) compared with ipilimumab alone.
“The PFS and ORR were numerically greater with nivolumab plus ipilimumab, but the combination was associated with more grade 3/4 adverse events,” he said. “The side effects were quite high with the combination, with about 30% of patients discontinuing due to treatment-related adverse events, as compared to 5% with nivolumab and 13% for ipilimumab.”
At baseline, about 90% of patients in all three treatment groups filled out PRO questionnaires on QoL, and after one or more treatments, about 80% completed them. By week 67, only 16 patients completed PRO assessments in each arm; attrition was highest in the ipilimumab arm, he noted.
At week 5, statistically significant reductions in global health occurred in all arms, but the changes were not clinically meaningful. The global health scores returned to baseline levels earlier for nivolumab (week 25) as compared to nivolumab plus ipilimumab and ipilimumab alone (week 31). Similar results were noted for QoL subscales.
“No clinically meaningful changes in global health were observed from baseline within 1 year, and no changes in any of the functional scales,” he said.
In conclusion, Dr. Schadendorf said that “even though the nivolumab plus ipilimumab arm had a higher frequency of adverse events, no clinically meaningful health-related QoL changes from baseline were observed in any of the treatment arms. The combination did not show any deterioration in health-related QoL compared to either treatment alone, even in the subgroup of patients experiencing grade 3/4 adverse events.”
He noted that one of the limitations of the study is that patients who discontinued treatment after experiencing progressive disease or adverse events, regardless of response, were not included in the analyses.
Further analyses and longer-term follow-up of health-related QoL data will confirm whether these findings hold up.