CHICAGO – Patients with advanced breast cancer whose aromatase inhibitor therapy was supplemented with a cycline-dependent kinase inhibitor had better progression-free survival with no drop in quality of life. Health-related quality of life for patients on the combination therapy was equivalent to that of patients on monotherapy in most aspects, but patients receiving both therapies had a sustained and clinically meaningful decrease in pain.
Also, the time to definitive deterioration by 10% or more of the global health status/quality of life scale score was similar between treatment arms (hazard ratio [HR] 0.944; 95% confidence interval [CI] 0.720-1.237).
The MONALEESA-2 trial had previously shown that the CDK 4/6 inhibitor ribociclib, when added to the aromatase inhibitor letrozole, significantly improved progression-free survival for postmenopausal patients with hormone receptor-positive, HER2 negative advanced breast cancer, when compared to letrozole in combination with placebo.
Sunil Verma, MD, reported on health-related quality of life and symptoms in the two arms of MONALEESA-2, reporting change from baseline, time to a definitive 10% deterioration, and the mean scores for on-treatment time compared to end of treatment on the global health status/quality of life subscale of the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-30).
“During treatment, overall health-related quality of life was maintained from baseline and was similar in both arms,” said Dr. Verma, the study’s first author. Changes during treatment were not statistically significant, and did not reach the predetermined threshold for a clinically meaningful difference. The effect of such key symptoms as fatigue, nausea, and vomiting on quality of life was similar regardless of whether patients received ribociclib or placebo, he said; though symptom scores were slightly higher for patients in the active arm of the study, the results were not clinically significant.
Reporting validated, cancer-specific patient-reported outcomes from the trial, Dr. Verma, professor and head of the department of oncology at the University of Calgary, (Alta.), sought to “highlight the patient experience with a focus on health-related quality of life and symptoms,” he said during his presentation at the annual meeting of the American Society of Clinical Oncology.
“A clinically meaningful – more than 5-point – improvement from baseline in pain score was maintained up to and including cycle 15 in the ribociclib plus letrozole arm,” said Dr. Verma. The placebo arm had a mild, clinically insignificant improvement at most assessment points. For both treatment arms, pain scores increased a bit above baseline levels at the time of disease progression or end of therapy, he said.
Patients completed the EORTC 30-item core quality of life questionnaire at their screening visit, and then every 8 weeks for the first 18 months. Then, they completed the questionnaires every 12 weeks until they experienced disease progression, died, were lost to follow-up or withdrew from the study, or stopped treatment.
Statistical analysis of the questionnaire results took into account the patients’ baseline scores, treatments received, and how they were stratified. Investigators assessed both statistical significance and the clinical meaningfulness of changes, defined as a change of 5-10 points.
In MONALEESA-2, 334 patients each were allocated to the ribociclib + letrozole arm and the placebo + letrozole arm. Patients in both arms, said Dr. Verma, were very compliant with questionnaire completion. Over 90% of patients who were eligible completed questionnaire through cycle 19 of ribociclib or placebo. He explained that the overall numbers completing the questionnaire declined with time, as more patients had disease progression.
It’s important to include these measures, he said, because patients and their families care about “the quality of the time gained,” so patient-reported outcomes should be a part of risk-benefit assessments for new cancer therapies. “While delaying disease progression may help to maintain patient quality of life, the addition of novel treatments to existing therapies can add toxicities, which may diminish quality of life,” said Dr. Verma.
Dr. Verma reported financial relationships with multiple pharmaceutical companies, including Novartis, which funded the study.
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