Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer : patient-reported outcomes from the FLIPPER trial

In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2− advanced breast cancer (ABC). We assessed health-related quality of life (QoL) using patient-reported outcomes (PROs). In this phase II double-blinded study, PROs were assessed at baseline after every three cycles and at the end of the treatment using the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23. Time to deterioration (TTD) in global health status (GHS)/QoL was defined as a decrease of ⩾10 points. Changes from baseline (CFB) and TTD were analysed using linear mixed-effect and Cox regression models, respectively. Of the 189 randomised (1:1) patients, 178 (94%) completed ⩾1 post-baseline assessment; 50% received ⩾22 cycles of study treatment, with a questionnaire compliance >90%. Mean baseline scores were comparable between arms. GHS/QoL scores were maintained throughout the palbociclib/fulvestrant treatment. CFB showed significant differences for GHS/QoL, appetite loss, constipation and systemic therapy side effect scores favouring placebo/fulvestrant. TTD in GHS/QoL was delayed in placebo/fulvestrant versus palbociclib/fulvestrant [30.3 versus 11.1 months; adjusted hazard ratio (aHR): 1.57, 95% CI: 1.03-2.39, p = 0.036]; this difference was not significant in patients with progressive disease (aHR: 1.2, 95% CI: 0.6-2.2, p = 0.658). No statistically significant differences in TTD were found for the other QLQ-C30 and QLQ-BR23 scales. Although TTD in GHS/QoL was prolonged with placebo/fulvestrant, no differences were observed on other functional or symptom scales. This finding and the improvement in PFS support the combination of palbociclib/fulvestrant as a beneficial therapeutic option for HR+/HER2− ABC. Sponsor Study Code: GEICAM/2014-12 EudraCT Number: 2015-002437-21 ClinTrials.gov reference: NCT0269048

HER2+ Breast Cancer Escalation and De-Escalation Trial Design: Potential Role of Intrinsic Subtyping

Long-term outcomes in breast cancer patients differ based on the molecular subtype, with HER2-E being the most aggressive one. Advances in clinical practice have dramatically shifted HER2+ breast cancer prognosis. Risk adapted strategies to individualize therapies are necessary. De-escalation approaches have been encouraged based on the risks of clinical-pathological factors. Molecular gene subtyping could further accurately define HER2 addicted tumours that are sensitive to anti-HER2 therapies, thus sparing unnecessary treatments. The transition from immunochemistry to molecular profiling in HER2+ breast cancer is discussed

HER2+ Breast Cancer Escalation and De-Escalation Trial Design: Potential Role of Intrinsic Subtyping

Classical clinical research has been developed according to immunohistochemical breast cancer subtypes, instead of designing trials specifically for each molecular subtype. Efforts in de-escalating treatment should focus on identifying a subgroup of HER2 oncogene addicted tumours that are especially sensitive to anti-HER2 therapies and, thus, spare unnecessary treatments. A prognostic assay that integrates molecular tumour features with clinical and pathologic variables and accurately defines a group of HER2 addicted tumours remains the best candidate among these strategies