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...

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Publicado en:Clinical Medicine Insights: Oncology Vol. 20; pp. 1 - 14
Autores principales: Azam, Faruque, Momtaz, Tanisha, Islam, Farzana, Rahman, Kazi Fatema, Shobnam, Sohana, Paul, Pulock, Alam, Md. Jawat
Formato: research tables/charts Journal Article
Publicado: Sage Publications Inc. 7/25/2026
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 7/25/2026
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      pub: Sage Publications Inc.
      place: Thousand Oaks, California
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        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
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