“This study shows for the first time that progression-free survival determination by imaging in a first-line clinical phase III trial indeed also reflects patients’ quality of life.”

— Nadia Harbeck, MD, PhD

Tweet this quote

IN PATIENTS WITH estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer, better quality of life may be prolonged by delaying the progression of the disease, according to an ongoing quality-of-life assessment from the PALOMA-2 study, presented by Nadia Harbeck, MD, PhD, of the Breast Cancer Center at the University of Munich, Germany, and colleagues, at the 2017 European School of Oncology (ESO)/ European Society for Medical Oncology (ESMO) International Consensus Conference for Advanced Breast Cancer (ABC4) in Lisbon, Portugal.¹ 

Analysis of trial data showed that patients whose disease took longer to progress had a significantly greater delay in the deterioration of health-related quality of life compared with patients whose disease progressed earlier, regardless of which treatment they had received. 

“This study is important because it shows for the first time that progression-free survival determination by imaging in a first-line clinical phase III trial indeed also reflects patients’ quality of life,” Dr. Harbeck told The ASCO Post. 

PALOMA-2 Trial 

PALOMA-2 IS an international, multicenter, double-blind, phase III clinical study that evaluated palbociclib (Ibrance) plus letrozole vs placebo plus letrozole in treatment-naive estrogen receptor–positive, HER2-negative advanced/metastatic breast cancer. In the trial, palbociclib demonstrated superiority over placebo in median progression-free survival. Patients who received the drug combination survived about 10 months longer without their disease progressing than did those who did not receive the combination: median of 24.8 months vs 14.5 months, respectively. 

This post-hoc analysis aimed to assess patient-reported health-related quality of life among patients in the study whose disease progressed compared with those whose disease did not, with a data cutoff of February 2016. “The reason we did this particular analysis is because the impact of delaying progression is very controversial, and there are not much data on the impact of delaying progression with regard to health-related quality of life in patients with metastatic breast cancer,” said Dr. Harbeck. 

Key Findings 

IN THE STUDY, 666 patients with estrogen receptor–positive, HER2-negative advanced/metastatic breast cancer were randomized 2:1 to receive either a combination of palbociclib and letrozole (n = 444) or placebo and letrozole (n = 222) as first-line treatment. 

Patients were asked about their physical, social/family, emotional and functional well-being, and additional breast cancer– specific concerns using the Functional Assessment of Cancer Therapy–Breast (FACT-B) questionnaire at baseline, on the first day of the second and third cycles, and on the first day of every other cycle from the fifth cycle until their disease progressed or until the end of treatment. “It’s very simple,” Dr. Harbeck explained. “Higher scores mean better quality of life.” 

Patients were divided into two groups by progression status (progressed vs not progressed) within each treatment arm at the time of data cutoff. Time to deterioration of health-related quality of life was defined as the duration of time between baseline and the first occurrence of a 7-point or greater decrease for the FACT-B total score, with no subsequent increase above the threshold. Median follow-up was 23 months. 

“In both treatment arms combined, we saw a statistically significant delay in the time to deterioration of quality of life in patients who had not progressed versus those who had progressed,” Dr. Harbeck noted. “This was highly statistically significant.” 

The investigators also evaluated the two treatment arms separately and found similar results in both the palbociclib and placebo groups: patients whose disease had not progressed at the time of data cutoff had about 10 months longer time to deterioration in quality of life than did patients whose disease had progressed. 

According to the investigators, these results imply that delay in progression-free survival may help to delay the deterioration of health-related quality of life in estrogen receptor–positive HER2-negative advanced/metastatic breast cancer. 

“I think this is a very important result for our patients,” said Dr. Harbeck. “These are data from the ongoing trial at each cycle, and you can see that progression is reflected in quality-of-life deterioration. So there is something, be it symptoms or other things, that patients associate with deterioration in their health-related quality of life, and we can pick this up with the progression-free survival endpoint.” 

Fatima Cardoso, MD

Additional Commentary 

CHAIR OF THE ABC4 Conference, Fatima Cardoso, MD, Director of the Breast Unit of the Champalimaud Cancer Centre in Lisbon, Portugal, commented in a press release: “Advanced breast cancer is, for the moment, an incurable disease, and, therefore, a balance between quantity and quality of life is of extreme importance to patients. The impact of any new treatment must be measured in both areas. The ESMO Magnitude of Clinical Benefit Scale, a tool developed to give an objective rate to all new treatments and currently used by a growing number of funders, classifies a therapy according to its efficacy in controlling the disease as well as its impact on the quality of life of patients. The use of patient-reported-outcomes is also crucial, since it is much more representative of what is relevant for the patient than evaluation of side effects done by physicians or nurses.” ■

DISCLOSURE: Dr. Cardoso reported no conflicts of interest. 

REFERENCE 

1. Harbeck N, Iyer S, Bhattacharyya H, et al: Impact of disease progression status on time to deterioration of patient reported health related quality of life in first-line ER+, HER2–advanced/metastatic breast cancer patients in the PALOMA-2 study. 2017 ABC4 International Consensus Conference. Abstract OR65. Presented November 2, 2017.