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To justify the dose regimen and dose modification scheme for patients with ABC, the pharmacokinetic (PK), safety, and efficacy data of ribociclib were analyzed. The data of several phase\u00a01\u20103 clinical studies were pooled and analyzed to characterize the relationship between exposure (dose or PK) and efficacy (progression\u2010free survival (PFS), time to response, and OS) or safety (neutropenia and QT interval prolongation). The exposure\u2013efficacy analysis showed no apparent relationship between ribociclib exposure and efficacy (PFS and OS), and efficacy analysis by dose reduction showed that patients with ABC continued to benefit from the treatment following dose reduction, supporting the starting dose of 600\u00a0mg as well as dose reductions to 400 and 200\u00a0mg. The exposure\u2013safety analysis showed that neutropenia and QT prolongation are related to ribociclib exposure that can be effectively managed by individualized dose modification (dose reduction\/interruption). Collective evidence from the exposure\u2013response analyses for efficacy and safety support the use of ribociclib in combination with ET partners at the starting dose of 600\u00a0mg, and also the effectiveness of individualized dose reductions in managing safety, while maintaining efficacy, in patients with HR+\/HER2\u2212 ABC. This analysis illustrates the utility of quantitative assessment in justifying dose selection and dose modification for oncology medicines.<\/jats:p>","DOI":"10.1002\/jcph.2310","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T07:10:40Z","timestamp":1689750640000},"page":"1359-1370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Quantitative Assessment of Ribociclib Exposure\u2013Response Relationship to Justify Dose Regimen in Patients with Advanced Breast Cancer"],"prefix":"10.1002","volume":"63","author":[{"given":"Yan","family":"Ji","sequence":"first","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Darstein","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Yang","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunava","family":"Chakravartty","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Zarate","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Yun","family":"Ho","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-4080-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-17-0627"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.09.019"},{"key":"e_1_2_10_6_1","unstructured":"Novartis Press Release. 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