Combination Therapy, Drug Interactions, and Survival Outcomes in Metastatic Breast Cancer: A Pooled Analysis of Phase II Trials.
Background: The relationship between regimen complexity, treatment sequencing, and survival outcomes in metastatic breast cancer (MBC) remains poorly characterized. Objectives: To quantify how treatment complexity, line of therapy, and baseline performance status (PS) differentially affect progressi...
| Publicado en: | Clinical Medicine Insights: Oncology Vol. 20; pp. 1 - 14 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Sage Publications Inc.
7/25/2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=195627448&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 195627448 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11795549 B3KT jtl: Clinical Medicine Insights: Oncology issn: 11795549 maglogo: Y pubinfo: dt: 7/25/2026 vid: 20 pid: 344 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 195627448 195627448 195627448 10.1177/11795549261473457 195627448 ppf: 1 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Combination Therapy, Drug Interactions, and Survival Outcomes in Metastatic Breast Cancer: A Pooled Analysis of Phase II Trials. aug: au: Azam, Faruque Momtaz, Tanisha Islam, Farzana Rahman, Kazi Fatema Shobnam, Sohana Paul, Pulock Alam, Md. Jawat affil: School of Pharmacy, BRAC University, Dhaka, Bangladesh sug: subj: Breast Neoplasms Drug Therapy Combined Modality Therapy Methods Neoplasm Metastasis Drug Therapy Antineoplastic Agents, Combined Treatment Outcomes Human Female Survival Analysis Progression-Free Survival Overall Survival Drug Synergism Drug Antagonism Drug Interactions Descriptive Statistics Data Analysis Software Kruskal-Wallis Test Mann-Whitney U Test Post Hoc Analysis Spearman's Rank Correlation Coefficient Confidence Intervals Funding Source Female ab: Background: The relationship between regimen complexity, treatment sequencing, and survival outcomes in metastatic breast cancer (MBC) remains poorly characterized. Objectives: To quantify how treatment complexity, line of therapy, and baseline performance status (PS) differentially affect progression-free survival (PFS) and overall survival (OS), and to identify synergistic and antagonistic drug combinations across MBC phase II trials. Methods: A systematic PubMed search (1992–2022) identified 892 eligible studies comprising 1,088 treatment arms and 53,672 patients. Objective response rate (ORR), median PFS, and median OS were extracted per arm along with molecular subtype, treatment size, therapy type, line of therapy, and weighted ECOG PS. Drug-drug interactions were inferred using a null model of non-interacting agents. Results: Adding agents improved both PFS and OS, but the PFS benefit was approximately twice the OS benefit (effect size, ε2 = 0.24 vs. 0.11; both p < 0.0001). Combination therapy progressively reduced the survival disadvantage associated with prior treatment, with PFS effect sizes declining from rrb = 0.55 (95% confidence interval [CI], 0.44–0.64) for single agents to 0.27 (0.09–0.44) for triplets. OS followed a similar pattern, decreasing from rrb = 0.58 (0.48–0.66) to 0.32 (0.14–0.48). ECOG PS showed an escalating correlation, from negligible for ORR (rs = −0.09, 95% CI −0.15 to −0.03) to medium for PFS (−0.23, −0.29 to −0.16) and very large for OS (−0.41, −0.48 to −0.35). Nine combinations showed response-based synergy, eight of which were cytotoxic doublets involving anthracycline-taxane or alkylator-anthracycline pairings; five pairs showed response-based antagonism with no consistent drug-class pattern. Conclusion: Combination therapy confers a substantially larger benefit for PFS than OS and partially compensates for the treatment-line penalty in patients with pretreated MBC. Patient fitness appears to become increasingly critical for long-term survival and may help guide regimen planning. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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