Physician discussion, October 23–26

Physician posts on X, October 23–26.

Four trials presented on October 26 are in the table: SWITCH and BRIDGET, now seventh and eighth for the congress, plus DESTINY-Breast09 and OptiTROP-Breast01. Their sections come first below, followed by OPTIMA (presented October 25) and the other trials presented October 23–25.

Days 3–4: October 25–26

1. SWITCH: a TOP1-inhibitor ADC with a new target, after a prior ADC

Phase 2 platform trial (NCT06649331), sponsored by Fudan University, in HER2-negative metastatic breast cancer after a prior ADC. Patients were assigned, based on their prior treatment, to one of four investigational ADCs from Jiangsu Hengrui, all with a topoisomerase I inhibitor (TOP1i) payload but each with a different target: SHR-A1811 (HER2), SHR-A1921 (TROP2), SHR-A2009 (HER3) or SHR-A2102 (Nectin-4). Lei Fan presented (4RO); Sherene Loi was the invited discussant. Confirmed ORR, the primary endpoint (investigator-assessed), was 0% (n=10), 8.3% (n=12), 0% (n=12) and 5.0% (n=20): 2 partial responses among 54 patients. No cohort met the prespecified Bayesian efficacy criterion (posterior probability of ORR above 20% greater than 0.80). Median PFS, a secondary endpoint, was 3.0, 1.4, 1.5 and 2.7 months. (ESMO 2026 4RO slides, Lei Fan; data cutoff Jul 31, 2026; median follow-up 8.6 months) Both responders had previously received disitamab vedotin, an ADC with a microtubule-inhibitor (MMAE) payload; 94.4% of patients had prior exposure to a TOP1i-based ADC. (ESMO 2026 4RO abstract) None of the four ADCs is FDA approved; their use in this setting is investigational. (KOL Pulse SWITCH page)

Physicians read SWITCH as evidence that resistance follows the payload, not the target. The counterpoint came from the clinic: for patients with brain metastases, ADCs are often the most active option left.

2. BRIDGET: tucatinib added after local therapy for isolated brain progression in HER2+ disease

Single-arm Phase 2 (NCT05323955) in HER2-positive metastatic breast cancer with isolated intracranial progression on trastuzumab/pertuzumab (TP) or T-DM1: after local therapy (radiosurgery or resection), tucatinib was added and the same backbone continued. Sarah Sammons presented (1767RO); the results are published in ESMO Open. The primary endpoint, intracranial PFS (RANO-BM), was met against a historical control: in 47 evaluable patients, median intracranial PFS was not reached vs a prespecified historical median of 5.0 months (one-sample log-rank P<0.0001). Intracranial PFS was 64% at 12 months and 59% at 18 months. (ESMO Open and 1767RO slides, Sarah Sammons; data cutoff Apr 17, 2026; median follow-up 19.6 months) Extracranial progression occurred in 2 patients (4.3%), and 46 of 47 were alive at the data cutoff. Grade 3 treatment-related AEs occurred in 32%, with no grade 4 or 5 treatment-related events; diarrhea was the most common (74%; grade 3, 11%). (ESMO Open; data cutoff Apr 17, 2026) Tucatinib (TUKYSA) is FDA approved with trastuzumab and capecitabine after one or more prior anti-HER2 regimens in the metastatic setting, including in patients with brain metastases, and with trastuzumab and pertuzumab as maintenance after induction (October 7, 2026). The BRIDGET strategy is investigational as tested, and tucatinib with T-DM1 is not FDA approved. (KOL Pulse BRIDGET page; FDA TUKYSA label, October 2026)

Physicians agreed the intracranial control was durable. They differed on whether a single-arm trial is enough to use the strategy now.

3. OptiTROP-Breast01: final overall survival with sac-TMT in pretreated metastatic TNBC

Phase 3, N=263, conducted in China (Kelun-Biotech): sacituzumab tirumotecan (sac-TMT), a TROP2 ADC, vs physician’s-choice chemotherapy in metastatic triple-negative breast cancer after at least two prior systemic therapies, at least one for metastatic disease. The primary endpoint, PFS by blinded independent central review, was met at the interim analysis; at the final PFS analysis, median PFS was 6.7 vs 2.5 months, HR 0.32 (95% CI 0.24–0.44). Overall survival, the key secondary endpoint, met its prespecified significance criterion at the interim analysis: HR 0.53 (0.36–0.78), one-sided P=0.0005. (Nature Medicine 2025; data cutoff Nov 30, 2023) Man Li presented the final OS analysis (4639RO), which the slides describe as descriptive: median OS 14.7 vs 9.9 months, HR 0.60 (95% CI 0.45–0.80), nominal P=0.0004; 24-month OS 33.8% vs 21.4%. 27.8% of the chemotherapy arm received a subsequent ADC; a prespecified RPSFT adjustment gave an HR of 0.55 (0.39–0.73). Grade ≥3 treatment-related AEs 64.6% vs 57.6%. (ESMO 2026 4639RO abstract and slides, Man Li; Annals of Oncology; final analysis, data cutoff Sep 17, 2025; median follow-up 29.4 months) Sac-TMT is approved in China (NMPA, November 2024) for this population. It is not FDA approved and is investigational in the US, where the TROP2 ADC approved in this setting is sacituzumab govitecan. (KOL Pulse OptiTROP-Breast01 page)

Physicians agreed the OS gain held at the final analysis. The open question was how to sequence TROP2 ADCs.

4. DESTINY-Breast09: first-line T-DXd + pertuzumab in patients with brain metastases

DESTINY-Breast09 is the Phase 3 trial (Daiichi Sankyo and AstraZeneca) of first-line trastuzumab deruxtecan (T-DXd) + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) in HER2-positive metastatic breast cancer. PFS by BICR, the primary endpoint, was 40.7 vs 26.9 months, HR 0.56 (95% CI 0.44–0.71), P<0.0001. (NEJM) The combination has been FDA approved since December 15, 2025 for first-line HER2-positive metastatic breast cancer; there is no separate brain metastases indication. (KOL Pulse DESTINY-Breast09 page) At ESMO 2026, Cristina Saura presented an exploratory analysis (LBA49) of the 61 patients with brain metastases at baseline confirmed by BICR (31 vs 30); these endpoints were not prespecified in the protocol. Median systemic PFS was 36.5 vs 11.1 months, HR 0.30 (95% CI 0.14–0.60). Median CNS-PFS was not estimable vs 9.7 months, HR 0.26 (0.11–0.57); 12-month CNS-PFS 88.9% vs 42.5%. The confirmed CNS response rate was 51.6% vs 26.7%. The slides advise caution because of the small number of patients. (LBA49 slides, Cristina Saura; data cutoff Feb 26, 2025; median follow-up 23.6 months)

Physicians called the intracranial results striking, and one called the regimen the standard of care for these patients. Jeff Ryckman, who works in radiation oncology, pointed to what the abstract did not report: prior local therapy to the brain and the split between active and treated brain metastases. Per the slides, included patients had brain metastases that were clinically inactive, or treated and asymptomatic.

5. OPTIMA: the 2-year cost analysis of test-directed chemotherapy

OPTIMA (ISRCTN42400492; UK NIHR, UCL and Warwick Clinical Trials Unit) randomized 4,429 patients with clinically high-risk HR+/HER2− early breast cancer, aged 40 or older, with 0–9 involved nodes to chemotherapy for all or to Prosigna (PAM50 ROR) test-directed treatment, in which only patients with an ROR score above 60 received chemotherapy. The efficacy primary endpoint, invasive breast cancer-free survival, met non-inferiority: HR 1.03 (90% CI 0.85–1.25) on the presented slide. (ASCO 2026 presented slide, Robert Stein; per-protocol population) The Abstract 500 text reports HR 0.99 (90% CI 0.81–1.20), non-inferiority p=0.013. (ASCO 2026 Abstract 500; median follow-up 3.9 years) On October 25, Peter S. Hall presented the prespecified 2-year within-trial economic evaluation of cost-effectiveness, OPTIMA’s other primary outcome per the trial registry and protocol, from the UK NHS perspective (LBA86; n=3,425 UK per-protocol participants). Test-directed treatment cost £654 less per patient (95% CI −£1,525 to £218, which crosses zero) and gave 0.05 more QALYs (0.02 to 0.08); 32% of the test-directed arm received chemotherapy. Lower chemotherapy costs (−£3,611 per patient) outweighed the £1,955 test. The investigators concluded that test-directed treatment dominated standard care over 2 years; a lifetime model is in progress. (ESMO 2026 LBA86 abstract and slides, Peter S. Hall; 2-year within-trial analysis) OPTIMA is a strategy trial, not a drug approval; Prosigna is an FDA-cleared test. (KOL Pulse OPTIMA page)

October 23–25: the most-discussed trials

6. NATALEE: 6-year overall survival with adjuvant ribociclib

Ribociclib + NSAI vs NSAI alone in stage II–III HR+/HER2− early breast cancer. 6-year OS 91.86% vs 89.73% (difference 2.1%); HR 0.809 (95% CI 0.661–0.989); nominal one-sided P=.019. Breast cancer–specific survival HR 0.706 (0.559–0.890). 6-year iDFS 83.23% vs 77.92%, HR 0.741 (0.646–0.849). (ESMO 2026 LBA25 abstract, Dennis Slamon; data cutoff May 15, 2026; median OS follow-up 66.5 months) Adjuvant ribociclib has been FDA approved since September 17, 2024. (KOL Pulse NATALEE page)

The debate was whether a 2.1-point OS difference with a nominal P value should change practice, and how much limited CDK4/6 inhibitor use after relapse in the control arm matters.

7. KEYNOTE-B49: pembrolizumab + chemotherapy in PD-L1–positive HR+/HER2− metastatic disease

Phase 3, N=342 (Merck): pembrolizumab or placebo added to chemotherapy in HR+/HER2− locally recurrent inoperable or metastatic breast cancer with PD-L1 CPS ≥1, after endocrine therapy. Hope S. Rugo presented the final analysis (LBA51), published the same day in Annals of Oncology. PFS by BICR, the primary endpoint, was 6.7 vs 6.0 months, HR 0.74 (95% CI 0.58–0.95), P=0.0089; 24-month PFS 15.0% vs 4.3%. In the CPS ≥10 subgroup (72 patients, a secondary endpoint), PFS HR was 0.59 (0.35–0.98). (ESMO 2026 LBA51 abstract and slides; interim analysis, data cutoff Sep 22, 2025) Overall survival, the key secondary endpoint, was 21.0 vs 22.2 months, HR 1.04 (0.81–1.33), P=0.6185, not met. Grade ≥3 treatment-related AEs 37.6% vs 32.7%; 3 treatment-related deaths (1.8%) with pembrolizumab vs none. (LBA51 slides; final analysis, data cutoff Mar 16, 2026) Pembrolizumab in HR+/HER2− breast cancer is investigational; its FDA-approved breast cancer indications are in triple-negative breast cancer. (KOL Pulse KEYNOTE-B49 page)

Physicians agreed the median PFS gain was small. The counterpoint was the tail of the PFS curve and the CPS ≥10 subgroup. A co-author of the study, Giampaolo Bianchini, called for better biomarkers. On October 25, Sherene Loi, a co-chair of Monday’s advanced breast cancer rapid oral session, pointed to early high-grade HR+ disease instead.

Modest median, longer tail

Giampaolo Bianchini @BianchiniGP

head of the breast cancer group, San Raffaele, Milan; KEYNOTE-B49 co-author · Oct 24

🔥 KEYNOTE-B49 meets its primary endpoint, but benefit seems limited to few patients 👉 ICIs benefit selected ER+/HER2− BC pts (CPS≥10, ER-low) 👉 Are ADCs better ICI partners than CT? 👉 What about PD-1/VEGF bispecifics? ➡️ Better biomarkers urgently needed! #ESMO26 https://t.co/xtA0X9K0CZ

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Stephanie Graff, MD, FACP, FASCO @DrSGraff

director of breast oncology, Brown University Health · Oct 24

KN-B49 @hoperugo PDL1+ HR+ MBC after ET tx w/chemo +/-Pembro Chemo: cape, doxil, taxanes Pembro improved mPFS 6 to 6.7 mos; no OS gain Complicated for practice w/ modest gain, ADCs in a competing space, and the pt burden of adding Pembro to oral cape. #ESMO26 @OncoAlert https://t.co/durudyjrCs

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Erika Hamilton, MD, FASCO @ErikaHamilton9

breast oncologist, Sarah Cannon Research Institute · Oct 24

KNB49 HR+ adv #bcsm with PDL+, chemo +/- pembro once chemo appropriate Only 19.4% of pts eligible (majority weren't PDL1+) ~79% of + were CPS 1-9 PFS improved 6 to 6.7 mo, but tail of curve much better at 24 mo 4.3 vs. 14% remaining on PFS CPS of 19 4.4 vs. 7.5 mos #ESMO26 https://t.co/pwtswREUTg

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Mustafa Özdoğan, MD @ozdogan_md

medical oncologist · Oct 24

STATISTICALLY POSITIVE. CLINICALLY THIN. KEYNOTE-B49: pembrolizumab + chemo delivered just +0.7 months median PFS in PD-L1 CPS≥1 HR+/HER2− advanced breast cancer with no OS benefit. Significance ≠ meaningful benefit. @hoperugo #ESMO26 https://t.co/KrBy46HOX1

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Sherene Loi, MD @LoiSher

breast medical oncologist, Peter MacCallum Cancer Centre · Oct 25

#keynoteB49- @myESMO #ESMO26 Adding ICB/ immunotherapy in advanced HR+ #breastcancer - wishful thinking 🤔 this context is immune deplete! -PFS 6-6.7 mo ➡️ Early high grade immune + HR + BC is the right place for it #ESMOAmbassadors https://t.co/nTuY30fwfU

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8. PANKU-Breast01: iza-bren vs chemotherapy in pretreated HR+/HER2− disease

Phase 3, N=383, conducted in China: iza-bren (izalontamab brengitecan, an EGFR×HER3 bispecific ADC) vs physician’s-choice chemotherapy. PFS by BICR 8.18 vs 4.01 months, HR 0.41 (95% CI 0.33–0.53), P<0.0001. ORR 40.5% vs 20.2%. OS immature. ILD in 2 patients (1.1%), grade 1–2. (ESMO 2026 LBA50 abstract, Bo Lan; data cutoff Jul 21, 2026) Grade ≥3 TRAEs 85.3% vs 65.8%; dose reductions 64.7% vs 28.5%; grade ≥3 neutropenia 53.7%, anemia 49.5%, thrombocytopenia 46.3% with iza-bren. (LBA50 slides) Iza-bren is investigational and not FDA approved in any indication.

Physicians noted the PFS and response gains. The questions were hematologic toxicity and sequencing after other ADCs.

Efficacy vs hematologic toxicity

Erika Hamilton, MD, FASCO @ErikaHamilton9

breast oncologist, Sarah Cannon Research Institute · Oct 23

#PANKUBreast01 Ph III results for iza bren (bispecific EGFR/HER3 ADC) vs TPC chemo, in previously treated HR +/HER- MBC 🔹mPFS: 4.0 vs. 8.1 mo, HR 0.41 🔹 ORR: 20% vs 40% 🔹 DoR: 4.2 vs. 6.9 mo 🔹 ILD: only 1.1% & all grade 1/2 #ESMO26 #ESMOAmbassadors https://t.co/ikHLXiLHX1

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Paolo Tarantino @PTarantinoMD

medical oncologist, Dana-Farber · Oct 23

🇨🇳 PANKU-Breast01: the HER3-EGFR bispecific TOPO1 ADC Iza-Bren improved PFS vs chemo in HR+/HER2- MBC (OS immature). High rate of hematologic toxicity, with ~50% G3+ anemia, neutropenia and thrombocytopenia, and most patients requiring dose reductions⚠️. #ESMO26 #ESMOAmbassadors https://t.co/f1zn2X0bpe

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Sherene Loi, MD @LoiSher

breast medical oncologist, Peter MacCallum Cancer Centre · Oct 23

#ESMO2026 Panku-breast01 Izabren sig. improves PFS in met HR+HER2 post CDK4i #BreastCancer 👏New targets 🎈impressive ORR too ➡️broadly comparable to DB04 - here all HER2 But 🎈haem tox Still have the what next issue 🤷🏻‍♀️ Online publication in @TheLancetOncol #ESMOAmbassadors #bcsm @OncoAlert @myESMO

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9. FOURLIGHT-1: atirmociclib, a CDK4-selective inhibitor, after a CDK4/6 inhibitor

Randomized Phase 2 (Pfizer): atirmociclib + fulvestrant vs investigator’s choice of endocrine-based therapy in HR+/HER2− advanced breast cancer after a CDK4/6 inhibitor. Antonio Giordano presented. Investigator-assessed PFS favored atirmociclib. Atirmociclib is investigational. Physicians pointed to the first-line Phase 3 trial, FOURLIGHT-3, as the next readout.

A co-author called the data strong. Others noted this is a Phase 2 result and that the control arm matters.

10. TALENT: neoadjuvant T-DXd in HR+/HER2-low early breast cancer

Phase 2, 132 patients, three arms: T-DXd alone, T-DXd + anastrozole, or T-DXd followed by docetaxel-cyclophosphamide. pCR (RCB0) 7% (3/45), 3% (1/29) and 9% (5/58). RCB0/1 16%, 17% and 17%. Grade ≥3 treatment-related AEs 24%, 17% and 28%; 3 cases of grade 2 ILD; 1 treatment-related death in the T-DXd-alone arm. (ESMO 2026 LBA23 slides, Sara A. Hurvitz) Neoadjuvant T-DXd is investigational. Enhertu is FDA approved in HER2-low breast cancer only for unresectable or metastatic disease. (KOL Pulse TALENT page)

Physicians called the pCR rates low. One noted that pCR is a limited surrogate endpoint in HR+ disease.

11. TROPION-Breast02: Dato-DXd in patients with brain metastases

Phase 3 (Daiichi Sankyo and AstraZeneca): datopotamab deruxtecan vs chemotherapy as first-line treatment for metastatic TNBC in patients who are not candidates for PD-1/PD-L1 therapy. Primary analysis: PFS by BICR 10.8 vs 5.6 months, HR 0.57 (95% CI 0.47–0.69), P<0.0001; OS 23.7 vs 18.7 months, HR 0.79 (0.64–0.98). (ESMO 2025 LBA21; data cutoff Aug 25, 2025; same medians and HRs in the May 22, 2026 FDA approval) Datroway has been FDA approved for this population since May 22, 2026. (KOL Pulse TROPION-Breast02 page) At ESMO 2026, Rebecca Dent presented an exploratory analysis of the patients with brain metastases at baseline (LBA96). In the patients with brain metastases at baseline (35 vs 26), median CNS PFS was 9.5 vs 2.6 months, HR 0.27 (95% CI 0.13–0.56). This analysis is exploratory. (LBA96 slide, Rebecca Dent, as tabulated on the KOL Pulse TROPION-Breast02 page; no data cutoff shown on the slide)

Physicians agreed the intracranial activity is real. They differed on whether it is ready for clinic, given the small, exploratory subgroup.

12. postMONARCH: final overall survival with abemaciclib after a CDK4/6 inhibitor

Phase 3, N=368 (Eli Lilly): abemaciclib + fulvestrant vs placebo + fulvestrant after progression on a CDK4/6 inhibitor plus endocrine therapy. Final OS (secondary endpoint): median 32.1 vs 24.6 months, HR 0.80 (95% CI 0.60–1.06), log-rank P=0.11, not statistically significant. Updated investigator-assessed PFS (primary endpoint): 5.9 vs 5.3 months, HR 0.78 (0.62–0.99), P=0.039. Exploratory PFS2 HR 0.76 (0.59–0.97) and time to chemotherapy HR 0.76 (0.58–0.99). (ESMO 2026 1RO slides, Kevin Kalinsky; data cutoff Mar 6, 2026; median follow-up 37 months) Abemaciclib after a CDK4/6 inhibitor is investigational; abemaciclib is FDA approved in other HR+/HER2− breast cancer settings. (KOL Pulse postMONARCH page)

Physicians read the OS result differently: a continued benefit for some, not a preferred second-line option for others, given biomarker-directed therapies.

13. APEX-Breast01: TQB2102, a biparatopic HER2 ADC, in HER2-low disease

Phase 3 (Chia Tai Tianqing): TQB2102 (rolditamig deuderuxtecan) vs physician’s-choice chemotherapy in HER2-low recurrent or metastatic breast cancer. Shusen Wang presented. PFS by blinded independent review, the primary endpoint in the HR+/HER2-low population, favored TQB2102. TQB2102 is investigational.

With HORIZON-Breast06 in the same session, physicians asked what a third HER2 ADC with a topoisomerase I payload adds when the comparator was chemotherapy, not T-DXd.

14. lidERA: patient-reported outcomes with adjuvant giredestrant

Phase 3, N=4,170 (Roche/Genentech): adjuvant giredestrant, an oral SERD, vs standard-of-care endocrine therapy (aromatase inhibitor or tamoxifen) in stage II–III HR+/HER2− early breast cancer. At the prespecified interim analysis, the primary endpoint, invasive disease-free survival, was met: 3-year iDFS 92.4% vs 89.6%, HR 0.70 (95% CI 0.57–0.87), P=0.0014. (SABCS 2025 GS1-10, Aditya Bardia; data cutoff Aug 8, 2025; median follow-up 32.3 months) On October 23, Gustavo Werutsky presented the patient-reported outcomes. More patients on giredestrant than on standard endocrine therapy reported never experiencing joint pain over the first 15 cycles, with comparable severity and interference. Hot flashes and fatigue were comparable, and physical functioning, role functioning and HRQoL were maintained in both arms. Over 50% of patients on giredestrant reported no bother from side effects across more than 3 years of treatment. (ESMO 2026 slides, Gustavo Werutsky; data cutoff Aug 8, 2025) Giredestrant is investigational: it is not FDA approved, and a regulatory submission has been filed. (KOL Pulse lidERA page)

Physicians read the PROs as support for giredestrant’s tolerability. The open question, which Yakup Ergün raised, is where an adjuvant oral SERD fits alongside CDK4/6 inhibitors: lidERA compared giredestrant with endocrine therapy alone, not with a CDK4/6 inhibitor plus endocrine therapy.

KOL Voices: the top breast cancer physicians at ESMO 2026

The top 10 physicians in the breast cancer tab of the ESMO 2026 KOL leaderboard, with one line from each and the trial it is about.

1. Yakup Ergün @dr_yakupergun · medical oncologist
   on KEYNOTE-B49 → “Evaluating immunotherapy in combination with ADCs or after ADC treatment may be more rational in today's treatment landscape.”
2. Paolo Tarantino @PTarantinoMD · medical oncologist, Dana-Farber
   on NATALEE → “Efficacy comparable to abema (monarchE), with different toxicity profile and wider population (N+ and high-risk N0).”
3. Erika Hamilton, MD, FASCO @ErikaHamilton9 · breast oncologist, Sarah Cannon Research Institute
   on FOURLIGHT-1 → “**1st line trial and curative trials coming!***”
4. Aya Mohamed | MSc, MD 🎗 @Dr_Oncologista · medical oncologist, breast cancer
   on postMONARCH → “Abemaciclib After CDK4/6 Inhibitor Progression — PFS Benefit Without a Statistically Significant OS Improvement”
5. Sara Tolaney @stolaney1 · chief of breast oncology, Dana-Farber
   on NATALEE → “6 yr OS HR 0.809 (delta 2.1%)”
6. Rebecca Shatsky, MD @Dr_RShatsky · breast medical oncologist, UC San Diego
   on FINER → “If we allow 40% de novo metastatic disease on a trial we can’t really say it’s representative of the general MBC population.”
7. Stephanie Graff, MD, FACP, FASCO @DrSGraff · director of breast oncology, Brown University Health
   on TALENT → “ypCR just isn’t the same endpoint w/ ER+ disease”
8. Matteo Lambertini, MD PhD @matteolambe · medical oncologist, University of Genova
   on KEYNOTE-B49 → “more translational research is needed to improve our understanding on how to optimize #immunotherapy use in luminal-like disease”
9. Kristina Jankovic, MD @JankovicK · medical oncology resident, Niš
   on APEX-Breast01 → “Impressive #APEXBreast01 data showing benefit with rolditamig deuderuxtecan over first-line chemotherapy in HR+/HER2-low metastatic #BreastCancer!”
10. Philippe Aftimos, MD  @aftimosp · medical oncologist, Institut Jules Bordet
    on FOURLIGHT-1 → “Next step: the FourLight-3 ph3 study in the 1L vs CDK4/6i”

What’s yet to come: the breast cancer highlights on October 27

ESMO 2026 ends on Tuesday, October 27. Times are Madrid time. Physician reactions will appear on the ESMO 2026 trials page as they post.

Related ESMO 2026 pages

FAQ

Which breast cancer trials did physicians discuss most at ESMO 2026?

By physician posts on X over October 23-26, NATALEE, KEYNOTE-B49, PANKU-Breast01, FOURLIGHT-1, TALENT and TROPION-Breast02 led. Of the trials presented on October 26, SWITCH had the most posts (21), followed by BRIDGET (17), DESTINY-Breast09 (14) and OptiTROP-Breast01 (12).

What did the SWITCH trial show?

In HER2-negative metastatic breast cancer after a prior ADC (94.4% had received a TOP1-inhibitor ADC), switching to an investigational TOP1-inhibitor ADC with a different target (HER2, TROP2, HER3 or Nectin-4) gave confirmed response rates of 0% to 8.3% (primary endpoint) and median PFS of 1.4 to 3.0 months (ESMO 2026 4RO slides, data cutoff July 31, 2026). Both responders had previously received disitamab vedotin, an ADC with an MMAE payload. None of the four ADCs is FDA approved.

Did sac-TMT improve overall survival in OptiTROP-Breast01?

Overall survival, the key secondary endpoint, met its prespecified significance criterion at the interim analysis (HR 0.53, one-sided P=0.0005; data cutoff November 30, 2023). At the final analysis, which was descriptive, median OS was 14.7 vs 9.9 months (HR 0.60, 95% CI 0.45-0.80, nominal P=0.0004; data cutoff September 17, 2025). Sac-TMT is approved in China and is not FDA approved.

Did NATALEE show an overall survival benefit at 6 years?

6-year OS was 91.86% vs 89.73% (HR 0.809, 95% CI 0.661-0.989) with a nominal one-sided P=.019 (ESMO 2026 LBA25 abstract, data cutoff May 15, 2026). Physicians disagreed on how much weight to give it. Adjuvant ribociclib has been FDA approved since September 17, 2024.

Did KEYNOTE-B49 improve survival with pembrolizumab in HR+/HER2- breast cancer?

PFS improved: 6.7 vs 6.0 months, HR 0.74 (95% CI 0.58-0.95), P=0.0089 (interim analysis, data cutoff September 22, 2025). Overall survival did not: 21.0 vs 22.2 months, HR 1.04 (0.81-1.33) (final analysis, data cutoff March 16, 2026). Pembrolizumab in HR+/HER2- breast cancer is investigational (ESMO 2026 LBA51, KOL Pulse KEYNOTE-B49 page).

Did postMONARCH improve overall survival?

Median OS was 32.1 vs 24.6 months (HR 0.80, 95% CI 0.60-1.06, log-rank P=0.11). The difference was not statistically significant (ESMO 2026, data cutoff March 6, 2026). Abemaciclib after a CDK4/6 inhibitor is investigational.

Is iza-bren approved?

No. Iza-bren is investigational. In PANKU-Breast01, PFS by BICR was 8.18 vs 4.01 months (HR 0.41, 95% CI 0.33-0.53) vs chemotherapy, with OS immature (ESMO 2026 LBA50 abstract).

What breast cancer sessions are left at ESMO 2026?

On Tuesday, October 27, the last day of ESMO 2026, Giuseppe Curigliano presents the breast cancer congress highlights (Scientific Congress Highlights 2, 11:40-12:20 Madrid time).