The Combination of Ribociclib plus Endocrine Therapy Improves Health-Related Quality of Life in Premenopausal Women with Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer

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For younger, premenopausal women, there are inherent difficulties related to breast cancer diagnosis and management that clinicians should consider. When facing the challenges of their diagnoses, younger women find it particularly important to maintain quality of life (QoL), and this poses a unique clinical challenge.1,2 Advanced breast cancer is generally associated with reduced QoL; however, improvement or stabilization of global QoL and specific disease-related symptoms can be achieved through appropriate treatment selection.

The MONALEESA-7 trial evaluated the safety and efficacy of the cyclin-dependent kinase 4/6 inhibitor (CDK4/6) ribociclib plus endocrine-based therapy in premenopausal patients with advanced breast cancer. Participants were randomized to receive either ribociclib or placebo, plus either a nonsteroidal aromatase inhibitor (letrozole or anastrozole) or tamoxifen. All patients received goserelin.3

In this phase 3 study, patient-reported outcomes were used to assess health-related QoL. In pre- and perimenopausal patients, previous reports had shown improvements in progression-free survival (PFS) and overall survival (OS) when ribociclib was combined with endocrine therapy.3,4

Currently, recommended first-line therapy for premenopausal women with hormone–receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer is endocrine therapy with ovarian suppression combined with a CDK4/6 inhibitor.5,6 Unfortunately, treatment resistance and disease progression eventually occur.

When compared with placebo, PFS was prolonged with ribociclib treatment, with a median of 13.0 months in the placebo arm and median 23.8 months in the treatment arm (P <.0001).3 The combination of ribociclib and endocrine therapy yielded a statistically significant longer OS rate, with a 29% reduction in the relative risk of death compared with placebo, and estimated OS rates of 70.2% compared with 46.0% at 42 months.4

At the beginning of each visit, patients were asked to complete assessment questionnaires and these were administered repeatedly throughout the course of treatment. This was to assist with the evaluation of patient-reported outcomes and included the use of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire core 30 (QLQ-C30) and Breast cancer module. The EQ-5D-5L was used to evaluate patient-reported outcome measures of health-related quality of life (HRQoL), treatment-related side effects and functioning, and disease symptoms.

Time to deterioration (TTD) 10% in the global health status and QoL scale and secondary patient-reported outcome variables of the EORTC QLQ-C30 were analyzed based on a 10-point threshold, which is considered the clinically meaningful threshold. A worsening in QoL score by 10% compared with baseline, with no subsequent improvement above this threshold observed during the treatment period, or death due to any cause, was the definitive 10% deterioration definition.

In the ribociclib arm, the improvement in global health status was complemented by a longer PFS. This was particularly meaningful because it implied that an improved QoL during treatment as well as a longer time without disease progression was demonstrated in patients receiving ribociclib. This probably played a role in driving longer TTD 10% in global health status.

In the ribociclib arm, there were 335 patients who had evaluable EORTC QLQ-C30 assessments, compared with 337 patients in the placebo arm. Patients treated with the combination of ribociclib and endocrine therapy showed a longer TTD ≥10% in global HRQoL. When a nonsteroidal aromatase inhibitor was prescribed, patients experienced similar benefits when combined with ribociclib, compared with placebo in terms of global HRQoL and pain.

The researchers concluded that HRQoL was preserved for a longer period of time when patients were treated with a combination of ribociclib and endocrine therapy. When these QoL findings are analyzed in light of previous reports of improved PFS and OS, there is strong and clear support of a clinical benefit-to-risk ratio in pre- and perimenopausal patients with HR+/HER2- advanced breast cancer.

Source

Harbeck N, Franke F, Villanueva-Vazquez R, et al. Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7). Ther Adv Med Oncol. 2020;12:1758835920943065.

References

  1. Radecka B, Litwiniuk M. Breast cancer in young women. Ginekol Pol. 2016;87:659-663.
  2. Mello Ramirez Medina J, de Araujo Trugilho I, Mendes GNB, et al. Advanced clinical stage at diagnosis of breast cancer is associated with poorer health-related quality of life: a cross-sectional study. Eur J Breast Health. 2018;15:26-31.
  3. Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19:904-915.
  4. Im SA, Lu YS, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381:307-316.
  5. Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol. 2018;29:1634-1657.
  6. NCCN clinical practice guidelines in oncology (NCCN Guidelines): breast cancer, version 3. 2019. www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed March 9, 2021.

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