HR+\/HER2\u2212 breast cancer\u00a0constitutes approximately\u00a065\u201375% of all breast cancer cases worldwide. Although CDK4\/6 inhibitors have\u00a0substantially extended\u00a0progression-free survival (PFS), up to 60% of patients derive no clinical benefit from these agents, underscoring the urgent need for more effective therapeutic strategies. Preclinical evidence has suggested synergistic antitumor activity when angiogenesis inhibitors are combined with CDK4\/6 inhibitors, prompting clinical investigation of this combinatorial approach.\u00a0<\/p>\n
Dr. Min Yan from the Department of Breast Disease at Henan Cancer Hospital led an investigator-initiated, single-center, open-label phase\u00a0Ib\/II trial to evaluate the triple combination of\u00a0famitinib,\u00a0dalpiciclib, and fulvestrant.\u00a0“Although preclinical evidence supports synergistic effects between antiangiogenic therapies and CDK4\/6 inhibitors, clinical data on this combination remain limited,”\u00a0Dr. Yan noted.\u00a0“We therefore initiated this trial to determine whether this regimen could address the substantial unmet clinical needs of the target patient population.”\u00a0The findings were published online in the\u00a0Chinese Medical Journal\u00a0on July 7, 2026.\u00a0<\/p>\n
A total of 46 eligible patients were enrolled. In the phase\u00a0Ib\u00a0dose-finding phase (n = 18), the recommended phase II dose (RP2D)\u00a0was\u00a0established\u00a0as\u00a0famitinib\u00a010 mg\u00a0daily plus\u00a0dalpiciclib\u00a0100 mg\u00a0daily in combination with fulvestrant. In the phase II cohort (n = 28), the confirmed objective response rate (ORR) was\u00a051.9%\u00a0and the disease control rate (DCR) was 92.6%, thereby meeting the prespecified efficacy<\/a> threshold for the first-stage analysis.\u00a0<\/p>\n However, the median PFS was 15.7 months, which did not\u00a0demonstrate\u00a0an advantage over current standard first-line regimens such as\u00a0ribociclib\u00a0plus fulvestrant, which has shown a median PFS of\u00a020.5 months\u00a0in similar patient populations.<\/p>\n
<\/p>\n The ORR observed in our trial was numerically higher, but this did not translate into a longer PFS. This may be attributable to the high rate of dose reductions necessitated by adverse events, which likely compromised dose intensity and long-term efficacy.”\u00a0<\/p>\n
Dr. Min Yan, Department of Breast Disease, Henan Cancer Hospital<\/p>\n
<\/p>\n Safety analyses revealed that the most common grade 3 or higher\u00a0(\u22653)\u00a0treatment-related adverse events\u00a0(TRAEs)\u00a0were hematologic, primarily decreased neutrophil count (96.4%),\u00a0decreased\u00a0leukocyte count (75.0%), and\u00a0decreased\u00a0platelet count (10.7%).\u00a0Nearly all\u00a0patients\u00a0required\u00a0dose reductions due to\u00a0adverse events.\u00a0The addition of\u00a0famitinib\u00a0exacerbated hematologic toxicities beyond those seen with either agent alone,\u00a0necessitating\u00a0frequent dose reductions that\u00a0likely undermined\u00a0treatment efficacy-a phenomenon the researchers attribute to a potential CYP3A4-mediated drug\u2013drug interaction between\u00a0famitinib\u00a0and\u00a0dalpiciclib.\u00a0<\/p>\n Exploratory biomarker<\/a> analyses did not show statistically significant differences in outcomes based on PIK3CA or BRCA1\/2 mutation<\/a> status, though patients with these mutations had numerically shorter PFS compared to wild-type groups.\u00a0<\/p>\n Due to the observed safety concerns and the lack of clear superiority over standard therapies, patient enrollment\u00a0was\u00a0terminated\u00a0early following a comprehensive benefit\u2013risk assessment.\u00a0<\/p>\n “Our findings suggest that angiogenesis inhibitors may not represent a preferred option in the frontline treatment of HR+\/HER2\u2212\u00a0breast cancer, but they may have greater potential in more aggressive subtypes like triple-negative breast cancer or refractory disease,”\u00a0concluded Dr. Yan.\u00a0<\/p>\n The researchers hope that this study\u00a0provides\u00a0valuable insights for future clinical trial design and underscores the importance of rational combination strategies and patient selection in oncology drug development.\u00a0<\/p>\n Source:<\/p>\n Chinese Medical Journals Publishing House Co., Ltd.<\/a><\/p>\n Journal reference:<\/p>\n Zhang, M., et al. (2026). Addition of angiogenesis inhibitors to CDK4\/6 inhibitors and fulvestrant in hormone receptor-positive, HER2-negative advanced breast cancer. Chinese Medical Journal.\u00a0DOI:\u00a010.1097\/CM9.0000000000004191.\u00a0https:\/\/www.ovid.com\/jnls\/cmj\/fulltext\/10.1097\/cm9.0000000000004191~addition-of-angiogenesis-inhibitors-to-cdk46-inhibitors-and<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"HR+\/HER2\u2212 breast cancer\u00a0constitutes approximately\u00a065\u201375% of all breast cancer cases worldwide. Although CDK4\/6 inhibitors have\u00a0substantially extended\u00a0progression-free survival (PFS), up…\n","protected":false},"author":2,"featured_media":909046,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[285086,64,63,17579,1617,4080,137,4082,5311,51491],"class_list":["post-909045","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-angiogenesis","tag-au","tag-australia","tag-breast-cancer","tag-cancer","tag-efficacy","tag-health","tag-hospital","tag-oncology","tag-preclinical"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/909045","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/comments?post=909045"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/909045\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media\/909046"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media?parent=909045"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/categories?post=909045"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/tags?post=909045"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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