{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:52:25Z","timestamp":1791478345611,"version":"4.3.4"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"abstract":"<jats:p>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 \u22123.10 versus \u22121.96 points with ribociclib plus a nonsteroidal aromatase inhibitor versus the aromatase inhibitor alone. Grade \u22653 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.<\/jats:p>","DOI":"10.1159\/ocl\/aebag020","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:28:48Z","timestamp":1791113328000},"source":"Crossref","is-referenced-by-count":0,"title":["Stage-specific quality of life and tolerability of CDK4\/6 inhibitors in HR-positive\/HER2-negative breast cancer: a narrative review"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-8300","authenticated-orcid":false,"given":"Luca","family":"Scafuri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Buonerba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Marotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Amato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germano","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Lorenzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,10,7]]},"container-title":["Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/ocl\/aebag020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:03:04Z","timestamp":1791475384000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/ocl\/aebag020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/ocl\/aebag020","archive":["Portico"],"relation":{},"ISSN":["0030-2414","1423-0232"],"issn-type":[{"value":"0030-2414","type":"print"},{"value":"1423-0232","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}