Suparna Wedam, Preeti Narayan, Haley Gittleman, Joyce Cheng, Vishal Bhatnagar, Hairat Sabit, Lauren S L Price, Nam Atiqur Rahman, Haw-Jyh Chiu, Nikolett Biel, Tiffany Ricks, Mallorie Fiero, Shenghui Tang, Christy Osgood, William Pierce, Richard Pazdur, Paul G Kluetz, Laleh Amiri-Kordestani
{"title":"美国食品和药物管理局批准：Inavolisib联合Palbociclib和Fulvestrant治疗内分泌耐药、pik3ca突变、激素受体阳性、人表皮生长因子受体2阴性、局部晚期或转移性乳腺癌","authors":"Suparna Wedam, Preeti Narayan, Haley Gittleman, Joyce Cheng, Vishal Bhatnagar, Hairat Sabit, Lauren S L Price, Nam Atiqur Rahman, Haw-Jyh Chiu, Nikolett Biel, Tiffany Ricks, Mallorie Fiero, Shenghui Tang, Christy Osgood, William Pierce, Richard Pazdur, Paul G Kluetz, Laleh Amiri-Kordestani","doi":"10.1200/JCO-25-00663","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The US Food and Drug Administration (FDA) approved inavolisib with palbociclib and fulvestrant for adults with endocrine-resistant, <i>PIK3CA</i>-mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer (MBC), as detected by an FDA-approved test, FoundationOne Liquid CDx assay, after recurrence on or after completing adjuvant endocrine therapy.</p><p><strong>Patients and methods: </strong>Approval was based on INAVO120, a randomized, double-blind, placebo-controlled trial in 325 patients with endocrine-resistant, <i>PIK3CA</i>-mutated, hormone receptor-positive, HER2-negative, locally advanced or MBC. Patients were randomly assigned (1:1) to either inavolisib (n = 161) or placebo (n = 164) in combination with palbociclib and fulvestrant.</p><p><strong>Results: </strong>INAVO120 met its primary end point of progression-free survival (PFS) by investigator assessment, with a median PFS of 15.0 months for inavolisib + palbociclib + fulvestrant versus 7.3 months for placebo + palbociclib + fulvestrant (hazard ratio [HR], 0.43 [95% CI, 0.32 to 0.59]; <i>P</i> < .0001). The objective response rate was 58% (95% CI, 50 to 66) versus 25% (95% CI, 19 to 32). The median duration of response was 18.4 months (95% CI, 10.4 to 22.2) versus 9.6 months (95% CI, 7.4 to 16.6). Interim analysis of overall survival did not reach statistical significance but was supportive of the overall benefit-risk assessment with a HR of 0.64 (95% CI, 0.43 to 0.97). Consistent with the PI3Kα inhibitor class, common adverse reactions noted with inavolisib included hyperglycemia, stomatitis, diarrhea, and rash.</p><p><strong>Conclusion: </strong>The approval of inavolisib with palbociclib plus fulvestrant was based on a statistically significant and clinically meaningful improvement in PFS observed in the INAVO120 trial. Before this approval, there were no specific therapies approved by the FDA for the first-line treatment of patients with endocrine-resistant, hormone receptor-positive advanced or MBC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3123-3131"},"PeriodicalIF":41.9000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant, <i>PIK3CA</i>-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Locally Advanced or Metastatic Breast Cancer.\",\"authors\":\"Suparna Wedam, Preeti Narayan, Haley Gittleman, Joyce Cheng, Vishal Bhatnagar, Hairat Sabit, Lauren S L Price, Nam Atiqur Rahman, Haw-Jyh Chiu, Nikolett Biel, Tiffany Ricks, Mallorie Fiero, Shenghui Tang, Christy Osgood, William Pierce, Richard Pazdur, Paul G Kluetz, Laleh Amiri-Kordestani\",\"doi\":\"10.1200/JCO-25-00663\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The US Food and Drug Administration (FDA) approved inavolisib with palbociclib and fulvestrant for adults with endocrine-resistant, <i>PIK3CA</i>-mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer (MBC), as detected by an FDA-approved test, FoundationOne Liquid CDx assay, after recurrence on or after completing adjuvant endocrine therapy.</p><p><strong>Patients and methods: </strong>Approval was based on INAVO120, a randomized, double-blind, placebo-controlled trial in 325 patients with endocrine-resistant, <i>PIK3CA</i>-mutated, hormone receptor-positive, HER2-negative, locally advanced or MBC. Patients were randomly assigned (1:1) to either inavolisib (n = 161) or placebo (n = 164) in combination with palbociclib and fulvestrant.</p><p><strong>Results: </strong>INAVO120 met its primary end point of progression-free survival (PFS) by investigator assessment, with a median PFS of 15.0 months for inavolisib + palbociclib + fulvestrant versus 7.3 months for placebo + palbociclib + fulvestrant (hazard ratio [HR], 0.43 [95% CI, 0.32 to 0.59]; <i>P</i> < .0001). The objective response rate was 58% (95% CI, 50 to 66) versus 25% (95% CI, 19 to 32). The median duration of response was 18.4 months (95% CI, 10.4 to 22.2) versus 9.6 months (95% CI, 7.4 to 16.6). Interim analysis of overall survival did not reach statistical significance but was supportive of the overall benefit-risk assessment with a HR of 0.64 (95% CI, 0.43 to 0.97). Consistent with the PI3Kα inhibitor class, common adverse reactions noted with inavolisib included hyperglycemia, stomatitis, diarrhea, and rash.</p><p><strong>Conclusion: </strong>The approval of inavolisib with palbociclib plus fulvestrant was based on a statistically significant and clinically meaningful improvement in PFS observed in the INAVO120 trial. Before this approval, there were no specific therapies approved by the FDA for the first-line treatment of patients with endocrine-resistant, hormone receptor-positive advanced or MBC.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"3123-3131\"},\"PeriodicalIF\":41.9000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO-25-00663\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO-25-00663","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant, PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Locally Advanced or Metastatic Breast Cancer.
Purpose: The US Food and Drug Administration (FDA) approved inavolisib with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer (MBC), as detected by an FDA-approved test, FoundationOne Liquid CDx assay, after recurrence on or after completing adjuvant endocrine therapy.
Patients and methods: Approval was based on INAVO120, a randomized, double-blind, placebo-controlled trial in 325 patients with endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, HER2-negative, locally advanced or MBC. Patients were randomly assigned (1:1) to either inavolisib (n = 161) or placebo (n = 164) in combination with palbociclib and fulvestrant.
Results: INAVO120 met its primary end point of progression-free survival (PFS) by investigator assessment, with a median PFS of 15.0 months for inavolisib + palbociclib + fulvestrant versus 7.3 months for placebo + palbociclib + fulvestrant (hazard ratio [HR], 0.43 [95% CI, 0.32 to 0.59]; P < .0001). The objective response rate was 58% (95% CI, 50 to 66) versus 25% (95% CI, 19 to 32). The median duration of response was 18.4 months (95% CI, 10.4 to 22.2) versus 9.6 months (95% CI, 7.4 to 16.6). Interim analysis of overall survival did not reach statistical significance but was supportive of the overall benefit-risk assessment with a HR of 0.64 (95% CI, 0.43 to 0.97). Consistent with the PI3Kα inhibitor class, common adverse reactions noted with inavolisib included hyperglycemia, stomatitis, diarrhea, and rash.
Conclusion: The approval of inavolisib with palbociclib plus fulvestrant was based on a statistically significant and clinically meaningful improvement in PFS observed in the INAVO120 trial. Before this approval, there were no specific therapies approved by the FDA for the first-line treatment of patients with endocrine-resistant, hormone receptor-positive advanced or MBC.
期刊介绍：
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
