Iter-4360dd15-0117-transcript
第 117 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 BOLERO-2 NEXT_FOCUS PFS HR median CI investigator-assessed"})【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ cal"}, {"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹 →"}, {"title": "Iter-4360dd15-0093-transcript", "tags": "iteration transcript", "modified": "20260424210654000", "preview": "!! 第 93 轮执行轨迹 → call list_recent({"n":6})
【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0116-reflection", "modified": "20260424215754000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424215754000", "tags": "pinned focus"}, {"title": "先锁定可读全文，再提取数值", "modified": "20260424215754000", "tags": "lesson evidence-chain trial-screening metadata-first"}, {"title": "Iter-4360dd15-0116-transcript", "modified": "20260424215747000", "tags": "iteration transcript"}, {"title": "BOLERO-2 主要终点具体结果数值（Springer OA）", "modified": "20260424215736000", "tags": "fact knowledge 4360dd15 clinical-trials evidence-chain"}, {"title": "Error-20260425-055456", "modified": "20260424215456000", "tags": "error iteration"}]}
→ call list_by_tag({"limit":20,"tag":"4360dd15"})
【tool:list_by_tag】
{"ok": true, "items": [{"title": "BOLERO-2 主要终点具体结果数值（Springer OA）", "modified": "20260424215736000"}, {"title": "BOLERO-2 可访问非-NEJM 设计/终点证据已补齐", "modified": "20260424215252000"}, {"title": "BOLERO-2 PMID 22149876 的可访问非-NEJM 设计/终点复核", "modified": "20260424215102000"}, {"title": "BOLERO-2 PMID 22149876 的第二独立复核来源与 primary endpoint", "modified": "20260424214827000"}, {"title": "BOLERO-2 原始主报告 PMID 22149876 与 primary endpoint PFS", "modified": "20260424214522000"}, {"title": "PMID 22149876 is the original BOLERO-2 phase 3 primary report, not 24267730", "modified": "20260424214401000"}, {"title": "PMID 24267730 is a subgroup analysis, not the first original human trial", "modified": "20260424214147000"}, {"title": "Iter-4360dd15-0106-four-candidate-audit", "modified": "20260424213752000"}, {"title": "Iter-4360dd15-0104-three-remaining-candidates-are-not-original-first-reports", "modified": "20260424213638000"}, {"title": "Iter-4360dd15-0103-EuropePMC-38310895-reference-parser-and-candidate-shortlist", "modified": "20260424213315000"}, {"title": "Iter-4360dd15-0100-human-trial-vs-non-original-screening-of-38310895-references", "modified": "20260424212530000"}, {"title": "Iter-4360dd15-0099-critic-mechanistic-vs-aging-trial", "modified": "20260424212312000"}, {"title": "Iter-4360dd15-0098-EuropePMC-extract-human-trial-PMIDs", "modified": "20260424212055000"}, {"title": "PMID 22367193 is cardiac-repolarization safety, not longevity evidence", "modified": "20260424210833000"}, {"title
→ call read_note({"title":"NEXT_FOCUS"})
→ call read_note({"title":"BOLERO-2 主要终点具体结果数值（Springer OA）"})
→ call read_note({"title":"BOLERO-2 可访问非-NEJM 设计/终点证据已补齐"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0116）\n\n直接读取 BOLERO-2 的公开全文，抓取主文中 investigator-assessed PFS 的精确 HR、95% CI、median 值和 PMID/PMCID。"}
【tool:read_note】
{"ok": true, "title": "BOLERO-2 主要终点具体结果数值（Springer OA）", "tags": "fact knowledge 4360dd15 clinical-trials evidence-chain", "text": "!! BOLERO-2 主要终点的具体结果数值（可访问权威全文）\n''结论'' 在可访问的 Springer Open Access 全文中，BOLERO-2 的主要终点（primary endpoint）= ''local investigator review 的 PFS''，最终分析结果为：\n\n- investigator review: median PFS ''7.8 vs 3.2 months''；''hazard ratio 0.45''（95% CI 0.38–0.54）；log-rank P < 0.0001\n- central review: median PFS ''11.0 vs 4.1 months''；''hazard ratio 0.38''（95% CI 0.31–0.48）；log-rank P < 0.0001\n\n''来源''\n- Springer Link open-access full text: BOLERO-2 Final Progression-Free Survival Analysis\n\n''可复现提取路径''\n1. web_search 锁定文章题名与可访问全文入口\n2. web_fetch 读取 Springer 全文摘要段\n3. 从 Abstract 的 Results 句直接提取 endpoint、median PFS、HR、CI、P 值\n\n''分析''\n这是对上一轮已确认的 trial metadata（phase 3、double-blind、randomized、primary endpoint=PFS by local investigator review）的数值补全，形成了从设计 → 终点 → 效应量 的闭环。"}
【tool:read_note】
{"ok": true, "title": "BOLERO-2 可访问非-NEJM 设计/终点证据已补齐", "tags": "fact knowledge 4360dd15 clinical-trials evidence-chain", "text": "!! BOLERO-2 的可访问非-NEJM 设计/终点证据已补齐\n\n''结论''\n已经找到一条''非 NEJM、可直接访问''且明确写出 BOLERO-2 试验设计和主要终点的权威来源：PMC/Annals of Oncology 的 BOLERO-2 OS 随访论文（PMID 25231953, PMCID PMC6267855）。\n\n''原文可直接复核的关键信息''\n- ''BOLERO-2 is a phase III, double-blind, randomized international trial''\n- 比较：everolimus 10 mg/day + exemestane 25 mg/day vs placebo + exemestane 25 mg/day\n- ''The primary end point was PFS as assessed by local investigator''\n- 同段还写明：''OS was a key secondary end point''\n\n''补充一致性来源''\n- eScholarship 的检索摘要同样显示：''phase 3, double-blind, randomized, international trial''，且 ''primary endpoint was PFS by local investigator review''。\n- ASCO 摘要检索结果也一致写明：''The primary end point was PFS by local investigator review.''\n\n''为什么这条证据足够''\n它满足当前最窄需求：\n1. 非 NEJM；\n2. 公开可访问；\n3. 明确写出 randomized / double-blind / phase III；\n4. 明确写出 primary endpoint = investigator-assessed PFS。\n\n''可复现检索路径''\n1. DuckDuckGo 搜索：BOLERO-2 investigator-assessed PFS phase III double-blind randomized\n2. 打开 PMC 文章：https://pmc.ncbi.nlm.nih.gov/articles/PMC6267855/\n3. 在摘要/Patients and methods 中核对上述句子。\n\n''警戒''\n不要再把 ClinicalTrials.gov 403 结果或仅有题录的页面当成主证据；当前任务已经可以用 PMC/ASCO/eScholarship 三方闭环结束。"}
→ call web_search({"limit":5,"query":"BOLERO-2 final progression-free survival analysis Springer open access PMID PMCID"})
→ call web_search({"limit":5,"query":"site:pmc.ncbi.nlm.nih.gov BOLERO-2 progression-free survival analysis PMID PMCID"})
→ call web_search({"limit":5,"query":"BOLERO-2 final progression-free survival analysis link.springer.com 10.1007/s12325-013-0060-1"})
【tool:web_search】
{"ok": true, "query": "BOLERO-2 final progression-free survival analysis Springer open access PMID PMCID", "results": [{"title": "Everolimus Plus Exemestane in Postmenopausal Patients with ... - Springer", "url": "https://link.springer.com/article/10.1007/s12325-013-0060-1", "snippet": "The final analysis of the primary endpoint from the BOLERO-2 study demonstrates that EVE+EXE is well tolerated and provides clinically meaningful PFS benefit versus EXE alone in the overall population of patients with HR + advanced BC progressing during/after NSAI therapy, irrespective of age, and among clinically relevant subsets of patients ..."}, {"title": "Everolimus plus exemestane for hormone-receptor-positive, human ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6267855/", "snippet": "The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR +), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors ..."}, {"title": "Everolimus plus exemestane in postmenopausal patients with HR ...", "url": "https://europepmc.org/article/MED/24158787", "snippet": "Everolimus plus exemestane in postmenopausal patients with HR (+) breast cancer: BOLERO-2 final progression-free survival analysis ."}, {"title": "PDF Everolimus Plus Exemestane in Postmenopausal Patients with
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov BOLERO-2 progression-free survival analysis PMID PMCID", "results": [{"title": "Progression-free or overall survival…revisited in BOLERO-2", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4080643/", "snippet": "Data presented by Dr. Piccart showed that after progression on study treatment, a somewhat higher fraction of subjects in the control arm received chemotherapy and a slightly higher fraction in the everolimus arm received further endocrine therapy. So how should we consider the results of BOLERO-2 trial?"}, {"title": "Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6233772/", "snippet": "This randomized clinical trial of 309 patients found a progression-free survival (PFS) benefit for everolimus plus exemestane over everolimus alone and a numerical PFS difference favoring capecitabine over combination therapy (note that imbalances among baseline parameters and potential informative censoring might have contributed to the PFS ..."}, {"title": "Everolimus Plus Exemestane for the Treatment of Advanced Breast Cancer ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4372651/", "snippet": "The primary end point of BOLERO-2 was progression-free survival (PFS) based on local assessment, and secondary end points included overall survival , objective response rate (ORR), quality of life (QoL), bone markers, and safety [23], [24]."}, {"title": "Evero
【tool:web_search】
{"ok": true, "query": "BOLERO-2 final progression-free survival analysis link.springer.com 10.1007/s12325-013-0060-1", "results": [{"title": "Everolimus Plus Exemestane in Postmenopausal Patients with ... - Springer", "url": "https://link.springer.com/article/10.1007/s12325-013-0060-1", "snippet": "The final analysis of the primary endpoint from the BOLERO-2 study demonstrates that EVE+EXE is well tolerated and provides clinically meaningful PFS benefit versus EXE alone in the overall population of patients with HR + advanced BC progressing during/after NSAI therapy, irrespective of age, and among clinically relevant subsets of patients ..."}, {"title": "Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast ...", "url": "https://www.springermedicine.com/everolimus-plus-exemestane-in-postmenopausal-patients-with-hr-br/23097536", "snippet": "Initial Breast Cancer Trials of OraL EveROlimus-2 ( BOLERO-2 ) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population."}, {"title": "PDF Everolimus Plus Exemestane in Postmenopausal Patients with ... - Springer", "url": "https://link.springer.com/content/pdf/10.1007/s12325-013-0060-1.pdf", "snippet": "Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis Denise A. Yardley • Shinzaburo Noguchi • Kathleen I. Pritchard Michael Gnant • Ga
→ call pubmed_search({"limit":5,"query":"\"BOLERO-2 Final Progression-Free Survival Analysis\" everolimus exemestane"})
→ call web_fetch({"max_chars":5000,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6267855/"})
→ call web_fetch({"max_chars":5000,"url":"https://link.springer.com/article/10.1007/s12325-013-0060-1"})
【tool:pubmed_search】
{"ok": true, "query": "\"BOLERO-2 Final Progression-Free Survival Analysis\" everolimus exemestane", "results": [{"pmid": "24158787", "title": "Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.", "source": "Adv Ther", "pubdate": "2013 Oct", "authors": ["Yardley DA", "Noguchi S", "Pritchard KI", "Burris HA 3rd", "Baselga J", "Gnant M", "Hortobagyi GN", "Campone M"], "url": "https://pubmed.ncbi.nlm.nih.gov/24158787/"}]}
【tool:web_fetch】
{"ok": true, "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6267855/", "status": 200, "content_type": "text/html; charset=utf-8", "text": "Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2 - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Ann Oncol . 2014 Sep 17;25(12):2357–2362. doi: 10.1093/annonc/mdu456 Search in PMC Search in PubMed View in NLM Catalog Add to search Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast canc
【tool:web_fetch】
{"ok": true, "url": "https://link.springer.com/article/10.1007/s12325-013-0060-1", "status": 200, "content_type": "text/html; charset=utf-8", "text": "Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis | Advances in Therapy | Springer Nature Link Skip to main content Advertisement Log in Menu Find a journal Publish with us Track your research Search Saved research Cart Home Advances in Therapy Article Everolimus Plus Exemestane in Postmenopausal Patients with HR + Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis Original Research Open access Published: 25 October 2013 Volume 30 , pages 870–884, ( 2013 ) Cite this article You have full access to this open access article Download PDF Save article View saved research Advances in Therapy Aims and scope Submit manuscript Everolimus Plus Exemestane in Postmenopausal Patients with HR + Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis Download PDF Denise A. Yardley 1 , Shinzaburo Noguchi 2 , Kathleen I. Pritchard 3 , Howard A. Burris III 1 , José Baselga 4 , Michael Gnant 5 , Gabriel N. Hortobagyi 6 , Mario Campone 7 , Barbara Pistilli 8 , Martine Piccart 9 , Bohuslav Melichar 10 , Katarina Petrakova 11 , Francis P. Arena 12 , Frans Erdkamp 13 , Wael A. Harb 14 , Wentao Feng 15 , Ayelet Cahana 15 , Tetiana Taran 15 , David Lebwohl 15 & … Hope S. Rugo 16 Show authors 24k Accesses 492 Citations 41 Altmetric 2 Mentions Explore al
→ call web_search({"limit":10,"query":"\"24158787\" PMCID BOLERO-2"})
→ call web_search({"limit":10,"query":"site:pmc.ncbi.nlm.nih.gov \"24158787\" everolimus exemestane"})
→ call web_search({"limit":10,"query":"\"Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis\" PMCID"})
【tool:web_search】
{"ok": true, "query": "\"24158787\" PMCID BOLERO-2", "results": [{"title": "Everolimus plus exemestane in postmenopausal patients with HR ...", "url": "https://europepmc.org/article/MED/24158787", "snippet": "Methods BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR + advanced BC with recurrence/progression during or after NSAIs."}, {"title": "Efficacy and toxicity of everolimus plus exemestane in third and later ...", "url": "https://jsurgmed.com/article/view/745731", "snippet": "PMID: 24158787 ; PMCID : PMC3898123. Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2 †."}, {"title": "National Center for Biotechnology Information", "url": "https://www.ncbi.nlm.nih.gov/pmc/resources/citations/3898123/export/", "snippet": "PMID- 24158787 OWN - NLM STAT- MEDLINE DCOM- 20140831 LR - 20220330 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 30 IP - 10 DP - 2013 Oct TI - Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. PG - 870-84 LID - 10.1007/s12325-013-0060-1 [doi] AB - INTRODUCTION: Effective ..."}, {"title": "Polymorphisms associated
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov \"24158787\" everolimus exemestane", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis\" PMCID", "results": []}
→ call web_fetch({"max_chars":4000,"url":"https://www.ncbi.nlm.nih.gov/pmc/resources/citations/3898123/export/"})
【tool:web_fetch】
{"ok": true, "url": "https://pmc.ncbi.nlm.nih.gov/resources/citations/3898123/export/", "status": 200, "content_type": "application/nbib", "text": "PMID- 24158787\r\nOWN - NLM\r\nSTAT- MEDLINE\r\nDCOM- 20140831\r\nLR - 20220330\r\nIS - 1865-8652 (Electronic)\r\nIS - 0741-238X (Print)\r\nIS - 0741-238X (Linking)\r\nVI - 30\r\nIP - 10\r\nDP - 2013 Oct\r\nTI - Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: \r\n BOLERO-2 final progression-free survival analysis.\r\nPG - 870-84\r\nLID - 10.1007/s12325-013-0060-1 [doi]\r\nAB - INTRODUCTION: Effective treatments for hormone-receptor-positive (HR(+)) breast \r\n cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor \r\n (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 \r\n (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly \r\n prolonged progression-free survival (PFS) versus placebo plus exemestane alone in \r\n this patient population. METHODS: BOLERO-2 is a phase 3, double-blind, \r\n randomized, international trial comparing everolimus (10 mg/day) plus exemestane \r\n (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) \r\n advanced BC with recurrence/progression during or after NSAIs. The primary \r\n endpoint was PFS by local investigator review, and was confirmed by independent \r\n central radiology review. Overall survival,
→ call write_note({"tags":["knowledge","fact","4360dd15","clinical-trials","evidence-chain"],"text":"!! BOLERO-2 公开全文的主文数值与书目信息已直接抽取\n\n''结论''\n从 Springer Open Access 全文及 NCBI citation export 可直接复核：\n\n- PMID: ''24158787''\n- DOI: ''10.1007/s12325-013-0060-1''\n- 文章题名：''Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.''\n- 试验类型：''phas)
【tool:write_note】
{"ok": true, "path": "C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\wiki\\tiddlers\\BOLERO-2_主文数值与_PMID_DOI_的直接抽取_Springer_OA_NCBI_export.tid", "title": "BOLERO-2 主文数值与 PMID/DOI 的直接抽取（Springer OA + NCBI export）"}
【assistant】
本轮已完成最窄子任务：把 BOLERO-2 公开全文的主文数值和书目信息从可访问来源直接抽出来了。
已确认：
- PMID: 24158787
- DOI: 10.1007/s12325-013-0060-1
- 试验类型：phase 3, double-blind, randomized, international trial
- primary endpoint：PFS by local investigator review
- investigator-assessed PFS：7.8 vs 3.2 months；HR 0.45（95% CI 0.38–0.54）；P < 0.0001
- central review PFS：11.0 vs 4.1 months；HR 0.38（95% CI 0.31–0.48）；P < 0.0001
我已把这条结果写入长期记忆：
- BOLERO-2 主文数值与 PMID/DOI 的直接抽取（Springer OA + NCBI export）
注意：
- 本轮的 NCBI citation export 里没有显式给出 PMCID，所以 PMCID 仍未被这轮直接证实。
<NEXT_FOCUS>用 PubMed / PMC 记录或其他权威索引，确认 PMID 24158787 是否对应 PMCID，以及如果没有 PMCID，就判定该 BOLERO-2 主文的可访问性边界。</NEXT_FOCUS>
```