Top KOLs Discussing BRIDGET
BRIDGET Key Slides & Visuals
ESMO 2026 slides
| Endpoint | Events, n (%) | Median | 6 months (95% CI) | 12 months (95% CI) | 18 months (95% CI) |
|---|---|---|---|---|---|
| Intracranial PFS (primary, RANO-BM) | 17 (36.2) | NR | 91% (79–97) | 64% (48–76) | 59% (42–73) |
| Extracranial PFS | 2 (4.3) | NR | 100% | 98% (84–100) | 98% (84–100) |
| Overall PFS (ESMO Open) | 17 (36.2) | NR | 89% (76–95) | 65% (49–77) | 62% (47–75) |
| Overall survival | 1 (2.1) | NR | 100% | 100% | 100% |
| Primary test | One-sample log-rank vs historical median iPFS 5.0 months: p < 0.0001 (met) |
| Endpoint | Events, n (%) | Median | 6 months (95% CI) | 12 months (95% CI) | 18 months (95% CI) |
|---|---|---|---|---|---|
| Intracranial PFS | 10 (40.0) | NR | 88% (67–96) | 62% (39–78) | 53% (30–73) |
| Extracranial PFS | 1 (4.0) | NR | 100% | 100% | 100% |
| Overall survival | 1 (4.0) | NR | 100% | 100% | 100% |
Same slides also posted by @DrSGraff, @dr_yakupergun, @kazuki_nozawa, @MamMa_mimumemo, @Dr_Oncologista, @matteolambe, @PTarantinoMD.
| Characteristic | n (%) |
|---|---|
| Age, mean (SD); range | 53.5 (12.09); 32–78 |
| Female | 46 (97.9) |
| ER positive | 31 (66.0) |
| Enrolled after first intracranial progression | 38 (80.9) |
| Enrolled after second intracranial progression | 9 (19.1) |
| Isolated CNS as site of first metastatic relapse | 25 (53.2) |
| Backbone trastuzumab/pertuzumab | 44 (93.6) |
| Backbone T-DM1 | 3 (6.4) |
| SRS-to-registration interval, median (IQR), days | 21.5 (15.0–37.0) |
Same slides also posted by @hoperugo.
Discussion: Dr Antonio Llombart-Cussac
Same slides also posted by @hoperugo.
Publication
Physician reactions to BRIDGET
Fantastic data by @drsarahsam in #BRIDGET showing the activity of #tucatinib in pts with 🧠 mets....used in combo w/ standard therapies..building upon what we saw in HER2CLIMB. ⬆️ unmet need! #ESMO26 #ESMOAmbassadors @OncoAlert https://t.co/1Rw2hsE4dh
Addition of Tucatinib to Trastuzumab/Pertuzumab After Local Therapy for Isolated Intracranial Progression in HER2-Positive Metastatic Breast Cancer: Primary Results of the Phase II BRIDGET Trial - ESMO Open https://t.co/DJ9hBUNXv3
Tucatinib added to HP is a nice option for 1L low volume brain only disease after local therapy. Particularly in patients with no extracranial disease where the toxicity of ADC is not desired. #ESMO26 https://t.co/ILYOutcThH
#ESMO26 nice summary by Antonio Llombart on CNS studies in mHER2 positive disease! Congrats to all. @OncoAlert https://t.co/7TnmuMZQod
BRIDGET evaluated tucatinib after local therapy for isolated CNS progression in HER2+ metastatic #BreastCancer , showing durable intracranial control in a Phase II study. Randomized data are still needed to confirm the benefit. @OncoAlert #ESMO26 @drsarahsam #ESMOAmbassadors https://t.co/Ip2nkxnS2E
Very exciting to have Bridget published simultaneously in @ESMO_Open available open access on line!! @drsarahsam @laura_huppert @PTarantinoMD @OncoAlert https://t.co/7PAh48KJoa
📌 BRIDGET: A phase II trial of tucatinib added to trastuzumab/pertuzumab or ado-trastuzumab emtansine after isolated intracranial progression in patients with advanced HER2-positive breast cancer ✨@drsarahsam #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF https://t.co/l0Vrfh5uHA
Very nice discussion by Antonio Llombart @OncoAlert #ESMO26 https://t.co/vSWZSoxytH
#ESMO2026 2 interesting presentations on HER2 isolated brain Mets and LMD. Tucatinib HP for brain Mets and IT HP for LMD. Remarkable efficacy for both! Impact on clinical practice. @OncoAlert https://t.co/RQMmPIPUki
興味深いと感じていたBRIDGET試験 (脳転移だけPDで、定位放射線治療の後で元の治療THまたはT-DM1にtucatinibを追加) 対象は47例で、66%は脳以外の病変がない状態でした。 頭蓋内PFSは中央値に達しておらず(histolical control中央値5か月を対照として、p<0.0001)、18か月時点の頭蓋内PFS率は59%でした。Grade 3以上の有害事象は15%でした。 脳転移PDでは、局所治療後にもとの全身治療を継続するというのはしばしば行われるプラクティスだけれど、さらにツカチニブ併用で長くなるか？を検討しています。histolical controlより長そうという想定でした。ランダム化ではないので、ツカチニブの追加効果がいかほどか？はわからないのですが、結果を見ると期待が持てる結果。ただ、日本ではTHやT-DM1にツカチニブを追加するというプラクティスが実際にいつ行えるかも不明なので、実臨床への影響はあまりないのですが。。。 #ESMO26
Context: the 1767RO abstract reported grade ≥3 adverse events in 15% (7/47); the ESMO Open paper reports grade 3 treatment-related adverse events in 32% (15/47), with no grade 4–5 treatment-related events.
Oral abstract #BreastCancer session at #ESMO26: phase II data on addition of #tucatinib to the ongoing anti-HER2 therapy in patients with advanced #HER2+ disease with brain-only relapse @OncoAlert @myESMO https://t.co/QgLVBXSDnX
#ESMO26 | BRIDGET A clinically valuable study addressing a real treatment dilemma in HER2+ breast cancer. Adding tucatinib after local therapy for isolated brain progression achieved 18-month intracranial PFS of 59% and extracranial PFS of 98%. Durable CNS control while maintaining an effective systemic regimen—a thoughtful strategy with compelling results. Congratulations to the investigators! @drsarahsam 👏
BRIDGET試験。 TPもしくはT-DM1中に、脳転移だけが進行した際に、局所療法後にtucatinibを追加するPhase 2試験。94%はTP base。 iPFSで12m時点で64%、18m時点で59%とhistorical controlと比べても良好な結果。 これはなかなかいい戦略に見える。 #ESMO26 https://t.co/ChVCMGH7vw
BRIDGET Trial (Phase II) #ESMO26 @drsarahsam Adding tucatinib after local therapy for isolated CNS progression in HER2+ metastatic breast cancer demonstrated durable intracranial control. 18-month intracranial PFS: 59% 18-month extracranial PFS: 98% Promising strategy for isolated CNS progression.
BRIDGET 🧠 @drsarahsam ❓does adding tucatinib to HP or TDM1 after isolated CNS progression improve IC-PFS in HER2+MBC 12mo IC-PFS = 64% 18mo IC-PFS=59% #ESMO26 @OncoAlert https://t.co/7iuThBVgqC
Primary results from BRIDGET ph2 trial presented by @drsarahsam and published in @ESMO_Open. Adding tucatinib to HP after an isolated intracranial PD led to impressively long PFS (59% free from PD or death at 18mo!!). Reasonable strategy from next Monday in TKI-naive patients. https://t.co/VvCfgdCBey
BRIDGET trial beautifully presented by @drsarahsam Adding tucatinib to HP after local therapy for isolated intracranial progression improved PFS in HER2+ MBC @OncoAlert #ESMO26 https://t.co/vIduedfDFh
At #ESMO26 Rapid oral abstracts session on advanced #breastcancer @drsarahsam presents BRIDGET 🧠 Adding tucatinib to Trastuzumab/Pertuzumab in HER2+ mBC with isolated intracranial progression ⬆️ brain disease control after local tx Rare extracranial PDs (n=2) @OncoAlert https://t.co/pu2vnxWAHZ
Potentially practice-changing results from the BRIDGET trial for HER2+ #MetastaticBreastCancer! Treating isolated brain mets progression with SRS + adding tucatinib to ongoing systemic therapy, rather than switching an otherwise effective treatment regimen. Promising findings for #BCBM! @OncoAlert #ESMO2026 #bcsm
🧠 When the brain progresses but the rest of the disease is controlled, do we really need to change everything? @OncoAlert At #ESMO26, phase II BRIDGET explores a very practical strategy in HER2+ metastatic #BreastCancer: After SRS for isolated intracranial progression, add tucatinib while continuing the existing HER2-directed backbone. 📊 47 evaluable patients ➡️ Median intracranial PFS: not reached ➡️ 6-month iPFS: 91% ➡️ 12-month iPFS: 64% ➡️ 18-month iPFS: 59% ➡️ Grade ≥3 AEs: 15% ➡️ Extracranial progression: 4.3% 🎯 Why this matters: isolated CNS progression does not necessarily mean the entire systemic strategy has failed. For me, this is a compelling example of site-specific treatment adaptation: treat the resistant compartment locally, reinforce CNS control with tucatinib, and preserve an otherwise effective systemic regimen. That may be one of the most clinically relevant forms of precision oncology. Excellent work from @drsarahsam @DrVanSwearingen @rashmikmurthy @CareyAnders1 and the BRIDGET investigators. Pinging @matteolambe @aftimosp @E_de_Azambuja @DrSGraff @ErikaHamilton9 @hoperugo @stolaney1 @BianchiniGP @kevinpunie @GaiaGriguolo #OncoAlert #ESMO26 #HER2 #BrainMetastases #Tucatinib #PrecisionOncology
Posted on October 23, from the 1767RO abstract, before the presentation. Context: the 1767RO abstract reported grade ≥3 adverse events in 15% (7/47); the ESMO Open paper reports grade 3 treatment-related adverse events in 32% (15/47), with no grade 4–5 treatment-related events.
Isolated brain progression in HER2+ MBC shouldn’t mean switching everything 🧠 BRIDGET: SRS + tucatinib added to ongoing HP/T-DM1 → 59% free of intracranial progression at 18 mo, vs a historical median of 5 mo. Keep what works, treat the brain. Practice-informing 🔥 To be Presented at #ESMO26 #OncoAlert4SIGHT
Posted on October 22, from the 1767RO abstract, before the presentation.
We are so excited to present the results of this unique but present population of isolated brain progression in HER2+ breast cancer. #bcsm https://t.co/TSbUfvagAF
Posted on October 22, before the presentation.
What physicians are weighing
Keep the backbone, treat the brain
Most physicians read BRIDGET as support for intensifying CNS control without abandoning a working systemic regimen. Paolo Tarantino, MD, called it a reasonable strategy in TKI-naive patients; Sarah Sammons, MD, wrote that tucatinib added to HP is a nice option for first-line low-volume brain-only disease after local therapy, particularly without extracranial disease; Erika Hamilton, MD, linked it to HER2CLIMB. The discussant, Dr Antonio Llombart-Cussac, concluded that isolated CNS progression should not automatically be considered systemic treatment failure, and in ESMO Insights described it as an opportunity to delay trastuzumab deruxtecan and reserve it for broader progression.
Single arm, historical control
Aya Mohamed, MD, wrote that randomized data are still needed, and Tatsunori Shimoi, MD, noted that without randomization the added effect of tucatinib cannot be sized. The historical median of 5.0 months was derived at trial design from the stable brain-metastasis subgroup of the HER2CLIMB control arm (CNS-PFS 5.6 months); the ESMO Open authors note cross-trial and cross-era limits, missing SRS-to-registration intervals for 13 patients, and concurrent endocrine therapy in 19 ER-positive patients as a potential confounder. Llombart-Cussac stressed that the population was enriched for well-controlled extracranial disease and that BRIDGET is not a replacement for trastuzumab deruxtecan.
Toxicity and the T-DXd era
Llombart-Cussac flagged diarrhea and hepatotoxicity as the toxicities to watch, along with adherence, cumulative toxicity, access and cost (ESMO Insights). The October 2026 TUKYSA label adds a boxed warning for hepatotoxicity. Only 3 patients received a T-DM1 backbone, so no conclusion can be drawn for tucatinib with T-DM1, and patients progressing after first-line T-DXd plus pertuzumab (DESTINY-Breast09) were not studied (ESMO Open).
Context: other CNS data in the same session
In the same session, an exploratory DESTINY-Breast09 analysis (LBA49, Cristina Saura) in 61 patients with baseline brain metastases reported CNS-PFS HR 0.26 (95% CI 0.11–0.57) and CNS confirmed ORR 51.6% vs 26.7% for T-DXd plus pertuzumab vs THP (LBA49 abstract and slides, interim data cutoff Feb 26, 2025; exploratory, not prespecified), and INSPIRE-LM (1768RO) reported intrathecal trastuzumab/pertuzumab for leptomeningeal disease. These are separate studies. DESTINY-Breast09 trial profile
BRIDGET Trial Design
BRIDGET (Secondary BRain metastases prevention after Isolated intracranial progression on trastuzumab/pertuzumab or T-DM1 in patients with aDvanced HER2+ brEast cancer with the addition of Tucatinib) asked whether adding a brain-penetrant HER2 tyrosine kinase inhibitor to an ongoing HER2 antibody backbone after local therapy can prolong intracranial disease control. It was conducted through the Hoosier Cancer Research Network and led by Duke University; the sponsor-investigator is Carey Anders, MD, with Pfizer as collaborator and funder. The trial started in March 2023 at US sites. Sarah Sammons, MD, presented the primary results at ESMO 2026 (1767RO), published simultaneously in ESMO Open.
Study Design
Single-arm, open-label, multicenter phase 2 (NCT05323955). One-sample log-rank test vs a historical exponential control (median iPFS 5.0 months); one-sided α 0.05, 90% power, 43 evaluable patients needed; 48 enrolled.
Population
HER2-positive MBC with a first or second isolated intracranial progression (or brain-only relapse) on TP or T-DM1, stable or absent extracranial disease, ECOG 0–2; no whole-brain radiation, leptomeningeal disease or prior HER2/EGFR TKI.
Interventions
SRS (with or without resection) to all new or progressive brain lesions, then tucatinib 300 mg twice daily added to ongoing TP or T-DM1 within 12 weeks; brain MRI every 9 weeks. Brain-only relapse off therapy started TP with tucatinib.
Endpoints
Primary: intracranial PFS (RANO-BM). Secondary: extracranial and overall PFS (RECIST 1.1), site of first progression, OS, toxicity; PROs and MRD.
Presenter & Discussant
Presenter Sarah Sammons, MD (University of Maryland). Discussant Dr Antonio Llombart-Cussac (Valencia). Corresponding author Carey Anders, MD (Duke).
Data Cut
April 17, 2026 (diagnosis and staging data updated through July 9, 2026); median follow-up 19.6 months.
BRIDGET in the News
BRIDGET Questions
What is the BRIDGET trial?
BRIDGET (NCT05323955) is a single-arm, open-label phase 2 trial run through the Hoosier Cancer Research Network and led by Duke University (sponsor-investigator Carey Anders, MD; funded by Pfizer). It enrolled patients with HER2-positive metastatic breast cancer who had a first or second isolated intracranial progression, with stable or absent extracranial disease, while on trastuzumab/pertuzumab (TP) or T-DM1. After stereotactic radiosurgery or resection, tucatinib 300 mg twice daily was added to the ongoing backbone. Design: Trial Design.
What did BRIDGET show at ESMO 2026?
The primary endpoint was met: median intracranial PFS (RANO-BM) was not reached and exceeded the prespecified historical median of 5.0 months (one-sample log-rank p < 0.0001). At a median follow-up of 19.6 months, intracranial PFS was 64% at 12 months and 59% at 18 months; extracranial progression occurred in 2 of 47 patients and 46 of 47 were alive (ESMO Open; data cutoff April 17, 2026). Figures: At a Glance.
Is this a randomized result?
No. BRIDGET is single-arm and compares against a historical benchmark (median intracranial PFS of 5.0 months, derived from the stable brain-metastasis subgroup of the HER2CLIMB control arm, CNS-PFS 5.6 months), so cross-trial and cross-era limits apply. Physicians, including Aya Mohamed, MD, noted that randomized data are still needed. A similar European trial, InTTercePT (UCBG-GINECO; NCT05041842), is testing a similar strategy in Europe.
What were the side effects?
In ESMO Open, grade 3 treatment-related adverse events occurred in 32% (15/47), with no grade 4 or 5 events; the most common were diarrhea (74%; grade 3, 11%), nausea (64%) and increased ALT (55%; grade 3, 11%). Three patients (6.4%) discontinued for adverse events, and 80.9% had at least one tucatinib dose delay or schedule change. The 1767RO abstract reported grade ≥3 adverse events in 15% (7/47); the ESMO Open paper, at the same median follow-up, reports 32% (15/47). The page shows both figures, labeled by source.
Is tucatinib approved for this use?
Tucatinib (TUKYSA) is FDA approved with trastuzumab and pertuzumab as maintenance for unresectable locally advanced or metastatic HER2-positive breast cancer following induction (approved October 7, 2026, based on HER2CLIMB-05), and with trastuzumab and capecitabine after one or more prior anti-HER2 regimens in the metastatic setting, including patients with brain metastases. The BRIDGET strategy, adding tucatinib after local therapy for isolated intracranial progression, comes from a single-arm phase 2 trial; HER2CLIMB-05, which supports the maintenance indication, enrolled patients with no progression after induction. Tucatinib with T-DM1 is not FDA approved. The October 2026 label carries a boxed warning for hepatotoxicity.
Who presented BRIDGET?
Sarah Sammons, MD (University of Maryland Greenebaum Comprehensive Cancer Center; @drsarahsam) presented abstract 1767RO on October 26, 2026, with simultaneous publication in ESMO Open. The invited discussant was Dr Antonio Llombart-Cussac (Arnau de Vilanova Hospital, Valencia).