Luca Scafuri, Carlo Buonerba, Vincenzo Marotta, Anna Rita Amato, Germano Guerra, Giuseppe Di Lorenzo
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引用次数: 0
Abstract
Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor tolerability should be interpreted alongside treatment benefit, patient-reported outcomes (PROs), and treatment continuation. This narrative review examines these outcomes in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic and early breast cancer.
Summary: In MONALEESA-2, median overall survival (OS) was 63.9 versus 51.4 months with ribociclib plus letrozole versus letrozole alone (hazard ratio [HR] 0.76), while global health-related quality of life (HRQoL) was maintained. PALOMA-2 and MONARCH 3 improved progression-free survival (HRs 0.58 and 0.540) without demonstrated OS improvement. Earlier CDK4/6 inhibitor use in SONIA increased exposure and toxicity without demonstrating improved OS or global HRQoL. In monarchE, with abemaciclib plus endocrine therapy versus endocrine therapy alone, seven-year invasive disease-free survival (iDFS) was 77.4% versus 70.9% (HR 0.734), and OS was 86.8% versus 85.0% (HR 0.842). NATALEE showed a 4.5-percentage-point five-year iDFS difference; its OS estimate remained uncertain. Three-year mean global-health-status changes in NATALEE were -3.10 versus -1.96 points with ribociclib plus a nonsteroidal aromatase inhibitor versus the aromatase inhibitor alone. Grade ≥3 diarrhea occurred in 7.8% of abemaciclib-treated monarchE patients. PALLAS and PENELOPE-B did not demonstrate improved iDFS; 42.2% of PALLAS palbociclib initiators discontinued early, including 27.2% because of adverse events.
Key messages: Global HRQoL, individual symptoms, and continuation answer different questions. Discussions about metastatic treatment should integrate disease control and sequencing; discussions about adjuvant treatment should address absolute recurrence reduction and planned duration. Both require consideration of baseline symptoms, uncertainty, and individual priorities.
期刊介绍：
Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.
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