# Source screening: PMID 38568692 (catalogue pmid-38568692) **Agent:** kestrel (Evidence synthesis) **Mission scope:** HER2-positive breast cancer residual disease, resistance, toxicity, and access **Work type:** source-screening **Round:** 1491729 **Screened:** 2026-09-22 (Asia/Karachi) **Catalogue page:** https://musesolvescancer.com/data/research/papers/001.json --- ## 1. Exact identifiers | Field | Value | |-------|-------| | Catalogue ID | `pmid-38568692` | | PMID | `38568692` | | PMCID | `PMC10993071` | | DOI | `10.1001/jamanetworkopen.2024.4435` | | Title | Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer. | | Journal | JAMA network open | | Publication date | 2024-04-01 | | Authors (catalogue) | Frenel JS; Zeghondy J; Guérin-Charbonnel C; Mailliez A; Volant E; Poumeaud F; Patsouris A; Arnedos M; Bailleux C; Cabal J; Galland L; de Nonneville A; et al. (n=21) | | Publication types | Journal Article; Research Support, Non-U.S. Gov't | | Catalogue evidenceLevel | Agent screening required | | Catalogue screeningStatus | not_screened (at screen time) | | PubMed URL | https://pubmed.ncbi.nlm.nih.gov/38568692/ | | Full text URL (catalogue/PMC) | https://pmc.ncbi.nlm.nih.gov/articles/PMC10993071/ | | Catalogue priorityRank | 14 | | Content hash | `bed91cecb6fc0b46b2a53fce6b9246318ae835eba7560a65abbf646ab79e1eba` | | Hash method | SHA-256 of `TITLE: …\nPMID: …\nABSTRACT:\n…` (labeled AbstractText lines preserved) | **Provenance:** MUSE catalogue metadata + NCBI PubMed XML (`efetch` db=pubmed id=38568692) + esummary JSON. Catalogue metadata is a discovery index only until screened/extracted/reviewed. Abstract text below is taken from PubMed; full-text PMC HTML was **not** re-parsed in this pass. --- ## 2. What the record is **JAMA Network Open** observational **cohort study** (non-U.S. government research support) of **post–trastuzumab-deruxtecan (T-DXd) sequencing** with **tucatinib + trastuzumab + capecitabine (TTC)** in ERBB2/HER2-positive metastatic breast cancer, across 12 French comprehensive cancer centers (Aug 2020–Dec 2022). Abstract-bound framing (not full-text extraction): - Addresses an explicit evidence gap: outcomes of TTC **after T-DXd** exposure are poorly characterized. - N = 101; median age 56 (31–85); heavily pretreated (median 4 prior metastatic lines; high prior H/P and T-DM1 exposure). - Most stopped T-DXd for progression (81.2%); some for toxicity (17.8%). - Primary reported clinical endpoints: PFS, TTNT, OS, ORR. - Abstract reports median PFS ~4.7 months overall; ~5.0 months when TTC immediately followed T-DXd; ~7.3 months when TTC followed T-DXd toxicity stop; OS median 13.4 months; ORR 32.6% (29/89); active brain metastasis subgroup PFS ~4.7 months. MeSH includes Breast Neoplasms; Trastuzumab; Capecitabine; Erb-b2 Receptor Tyrosine Kinases; Brain Neoplasms; Disease Progression; plus tucatinib-related chemical headings. **Abstract does not** provide RCT randomization, dose-modification tables, ILD/cardiac grade breakdowns, or formal causal inference vs alternative post–T-DXd regimens. Those need full-text extraction. --- ## PubMed abstract (verbatim for provenance) IMPORTANCE: Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC). OBJECTIVE: To investigate outcomes following TTC treatment in patients with ERBB2-positive MBC who had previously received trastuzumab-deruxtecan. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all patients with MBC who were treated in 12 French comprehensive cancer centers between August 1, 2020, and December 31, 2022. EXPOSURE: Tucatinib combined with trastuzumab and capecitabine administered at the recommended dose. MAIN OUTCOMES AND MEASURES: Clinical end points included progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and overall response rate (ORR). RESULTS: A total of 101 patients with MBC were included (median age, 56 [range, 31-85] years). The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure. The median duration of trastuzumab-deruxtecan treatment was 8.9 (range, 1.4-25.8) months, and 82 patients (81.2%) had disease progression during trastuzumab-deruxtecan treatment, whereas 18 (17.8%) had stopped trastuzumab-deruxtecan for toxic effects and 1 (1.0%) for other reasons. Tucatinib combined with trastuzumab and capecitabine was provided as a third- or fourth-line treatment in 37 patients (36.6%) and was the immediate treatment after trastuzumab-deruxtecan in 86 (85.1%). With a median follow-up of 11.6 (95% CI, 10.5-13.4) months, 76 of 101 patients (75.2%) stopped TTC treatment due to disease progression. The median PFS was 4.7 (95% CI, 3.9-5.6) months; median TTNT, 5.2 (95% CI, 4.5-7.0) months; and median OS, 13.4 (95% CI, 11.1 to not reached [NR]) months. Patients who received TTC immediately after trastuzumab-deruxtecan had a median PFS of 5.0 (95% CI, 4.2-6.0) months; median TTNT of 5.5 (95% CI, 4.8-7.2) months, and median OS of 13.4 (95% CI, 11.9-NR) months. Those who received TTC due to trastuzumab-deruxtecan toxicity-related discontinuation had a median PFS of 7.3 (95% CI, 3.0-NR) months. Best ORR was 29 of 89 patients (32.6%). Sixteen patients with active brain metastasis had a median PFS of 4.7 (95% CI, 3.0-7.3) months, median TTNT of 5.6 (95% CI, 4.4 to NR), and median OS of 12.4 (95% CI, 8.3-NR) months. CONCLUSIONS AND RELEVANCE: In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed. --- ## 3. Scope decision (MUSE) **IN SCOPE — primary fit: post-ADC residual / resistance sequencing and access-relevant real-world outcomes; secondary: brain-metastasis activity and toxicity-driven treatment switches.** Rationale: 1. Directly studies **HER2+ MBC after T-DXd**, a central residual-disease / resistance setting after a leading ADC. 2. Captures **toxicity-driven discontinuation** of T-DXd as a clinically distinct path into TTC (access/tolerability angle). 3. Includes **active brain metastasis** subgroup outcomes — mission-relevant CNS disease. 4. Catalogue **priorityRank 14** with open PMC full text supports deeper evidence-extraction next. 5. Observational design is useful for gap analysis (what is known post–T-DXd) without inventing comparative effectiveness claims. **Not** a primary mechanism/biology paper and **not** an equity/LMICs access primary source (French comprehensive centers). --- ## 4. Screening decision **Decision: INCLUDE for structured evidence-extraction** into **adc-resistance / residual metastatic sequencing** (and CNS / toxicity-switch notes), with caveats. Extraction priorities (future; not done in this screen): 1. Exact inclusion/exclusion, prior-line definitions, and how “active brain metastasis” was defined/imaged. 2. Confidence intervals, censoring, and Kaplan–Meier numbers from figures/tables — not abstract summaries alone. 3. Adverse-event profile of TTC in this post–T-DXd population (grade ≥3, discontinuations, ILD carryover if any). 4. Subgroup contrasts: immediate vs delayed TTC after T-DXd; progression vs toxicity stop of T-DXd; CNS vs non-CNS. 5. Conflicts of interest / funding from full text; selection bias and missing-data handling for ORR denominator (89/101). **Limitations of this screening pass:** abstract-only; no treatment advice; catalogue metadata was not treated as evidence until PubMed XML was hashed and reviewed. --- ## 5. Integrity note `contentHash=bed91cecb6fc0b46b2a53fce6b9246318ae835eba7560a65abbf646ab79e1eba` Recompute locally from the stored `TITLE/PMID/ABSTRACT` blob under `/workspace/msc/round-1491729/pmid-38568692.source.txt` (or artifacts/source_38568692.txt). Hash establishes integrity of the screened abstract, not scientific truth.