Table of Contents

Major Presentations and Milestones

DESTINY-Breast05 Trial design, results, and conclusions

DESTINY-Breast05 Sentiments and Criticisms

DESTINY-Breast05 Temporal Sentiment Arc

Professional Resources : Interactive Tweet History, Influence Diagram, Sentiment Table, AI Chatbot

DESTINY-Breast05 Trial: Major Presentations and Milestones

Primary speakers driving the story

DESTINY-Breast05 (also referenced as NSABP B-60) emerged as a major “curative-setting ADC” inflection point at ESMO 2025, with subsequent consolidation at SABCS 2025 and journal amplification through NEJM. Multiple tweets attribute the ESMO 2025 presidential-session presentation to Charles E. Geyer, MD (e.g., Susan G. Komen and UPMC Hillman Cancer Center), while several clinician posts emphasize the role of Sara Tolaney, MD in discussion and practice-context framing.

At ESMO 2025, Paolo Tarantino, MD framed the headline visually and clinically: “The KM curve of 2025: among high risk patients with HER2+ eBC and RD, adjuvant T-DXd halved the risk of recurrence vs T-DM1… 10.8% rate of ILD, 3 deaths. Remember to monitor the lungs!” https://x.com/PTarantinoMD/status/1979565393258979341

At the same meeting, Sherene Loi, MD emphasized both the efficacy and the tolerability/ILD tradeoff, while also highlighting a clinically important pattern signal: “balanced with ~10%ILD but 👏less CNS 🧠recurrences 🙌 … Bravo to those >70% patients putting up with all that nausea!!” https://x.com/LoiSher/status/1979569939053965747

By SABCS 2025, attention shifted from “practice-changing efficacy” to implementation in a real-world adjuvant pathway—particularly how to manage ILD risk and how to handle overlap with neoadjuvant DESTINY-Breast11. Hope Rugo, MD highlighted safety data addressing a key operational question: “Most encouraging is the lack of an increase in ILD/pneumonitis when TDXd is given through adjuvant RT.” https://x.com/hoperugo/status/1998834573153620142

NEJM’s meeting post further codified the benefit–risk framing: “trastuzumab deruxtecan improved invasive disease–free survival but carried a risk of interstitial lung disease.” https://x.com/NEJM/status/1998831253207109965

DESTINY-Breast05 Trial Design, Results, and Conclusions

Trial Design:

From the tweet dataset, DESTINY-Breast05 is a phase 3 post-neoadjuvant (“residual disease”) trial in HER2-positive early breast cancer comparing trastuzumab deruxtecan (T-DXd) versus T-DM1 for patients with residual invasive disease after neoadjuvant therapy, with eligibility repeatedly described as a high-risk subset (e.g., inoperable at baseline and/or node-positive residual disease). Oncology Brothers summarized: “PhIII, TDXd vs. TDM1 in high risk (inoperable or LN+) residual disease after NeoAdj chemo for Her2+ Breast Cancer.” https://x.com/OncBrothers/status/1998909578906578951

Erika Hamilton, MD underscored the “do not overgeneralize” implementation point from Sara Tolaney, MD: “Should not use T-DXd in ALL HER-2 + #bcsm with residual disease- only those that met trial entry..really unresectable large size or node positive.” https://x.com/ErikaHamilton9/status/1979568034734838042

Primary Results (iDFS / invasive recurrence or death):

Across tweets, the magnitude of benefit is consistently described as large, with hazard ratios around ~0.47 and “~50%” relative risk reduction versus T-DM1.

Yakup Ergün, MD provided a compact quantitative summary: “iDFS HR 0.47, 3-yr iDFS 92.4% vs 83.7% … Major reduction in distant relapse (HR 0.49) and early signal of lower CNS events … Benefit consistent across HR status, nodal burden, operability, and HER2 strata.” https://x.com/dr_yakupergun/status/1999085685886578712

NSABP Foundation similarly emphasized the relative effect size: “T-DXd reduced risk of invasive disease recurrence or death by 53% vs T-DM1…” https://x.com/NSABPFoundation/status/1980321354017800396

Distant relapse / CNS signals:

Multiple tweets highlighted distant relapse reduction and a possible CNS signal. Ergün cited “HR 0.49” for distant relapse and “early signal of lower CNS events.” https://x.com/dr_yakupergun/status/1999085685886578712

Loi similarly noted “👏less CNS 🧠recurrences” while cautioning on ILD and nausea burden. https://x.com/LoiSher/status/1979569939053965747

Safety (ILD/pneumonitis as the defining tradeoff):

ILD risk was repeatedly foregrounded as the key counterweight to efficacy. Tarantino reported: “10.8% rate of ILD, 3 deaths.” https://x.com/PTarantinoMD/status/1979565393258979341

Loi described “~10%ILD” and highlighted substantial nausea burden: “Bravo to those >70% patients putting up with all that nausea!!” https://x.com/LoiSher/status/1979569939053965747

NEJM’s SABCS 2025 post reinforced the same clinical framing: improved iDFS “but carried a risk of interstitial lung disease.” https://x.com/NEJM/status/1998831253207109965

Radiation timing and ILD:

One of the most practice-relevant safety questions is whether adjuvant RT timing modifies ILD risk. Hope Rugo, MD summarized: “Most encouraging is the lack of an increase in ILD/pneumonitis when TDXd is given through adjuvant RT.” https://x.com/hoperugo/status/1998834573153620142

Oncology Brothers echoed: “Timings of RT did NOT impact the severity incidence or severity of ILD.” https://x.com/OncBrothers/status/1998909578906578951

Key Conclusions:

In the tweet-level discourse captured here, DESTINY-Breast05 is widely viewed as practice-changing for a high-risk subset of HER2+ early breast cancer with residual disease after neoadjuvant therapy, establishing T-DXd as a likely successor to T-DM1 in that setting. The dominant implementation caveats are (1) strict adherence to the trial’s high-risk eligibility boundaries, and (2) rigorous ILD monitoring/management, particularly as clinicians consider how to integrate T-DXd across perioperative regimens (DESTINY-Breast11 overlap) and adjuvant RT workflows.

DESTINY-Breast05 Sentiments and Criticisms

Positive Reception:

Paolo Tarantino, MD: “adjuvant T-DXd halved the risk of recurrence vs T-DM1… New SoC…” https://x.com/PTarantinoMD/status/1979565393258979341

Aya Mohamed, MSc, MD: “The @NEJM DESTINY-Breast05 trial is practice-changing: T-DXd cut recurrence/death risk by ~53% vs T-DM1…” https://x.com/Dr_Oncologista/status/1998891109326659618

Mustafa Özdoğan, MD framed the broader “curative-setting ADC” shift: “A new era in early HER2+ breast cancer… Bringing ADCs into the curative setting. Lung monitoring remains essential.” https://x.com/ozdogan_md/status/1979585523829055684

Critical Perspectives / Cautions:

Erika Hamilton, MD (relaying Tolaney’s caution): “Should not use T-DXd in ALL HER-2 + #bcsm with residual disease- only those that met trial entry..really unresectable large size or node positive” https://x.com/ErikaHamilton9/status/1979568034734838042

Sherene Loi, MD emphasized the benefit-risk balance and symptom burden: “impressive efficacy… balanced with ~10%ILD… Bravo to those >70% patients putting up with all that nausea!!” https://x.com/LoiSher/status/1979569939053965747

Michael Lam, PharmD raised a generalizability/access concern: “DESTINY-Breast05 has minimal US enrollment… There is a major disconnect between the study population and real-world usage.” https://x.com/pharmatinib/status/1999355295823458767

Where the debate concentrates (DB-05 vs DB-11 overlap):

As DESTINY-Breast11 (neoadjuvant) and DESTINY-Breast05 (post-neoadjuvant residual disease) both reported positive signals, clinicians immediately focused on sequencing and eligibility boundaries. Stephanie Graff, MD explicitly asked: “What are we doing in the overlapping population?” https://x.com/DrSGraff/status/1979804975736963127

Elisa Agostinetto, MD reinforced a strict-criteria approach: “I would recommend post-neoajuvant T-DXd only in the DB-05 criteria… and not for all cases of residual disease! T-DM1 is still SoC for these cases” https://x.com/ElisaAgostinett/status/1980655015355380176

DESTINY-Breast05 Temporal Sentiment Arc

ESMO 2025 (initial “practice-changing” reveal with ILD front-and-center)

Primary/KOL tweets:

• https://x.com/PTarantinoMD/status/1979565393258979341
• https://x.com/ErikaHamilton9/status/1979568034734838042
• https://x.com/ozdogan_md/status/1979585523829055684
• Tone: Strong enthusiasm around a large iDFS effect size, immediately tempered by ILD mortality and tolerability burden (nausea), with early calls to adhere strictly to eligibility criteria.
• Shift: From “T-DXd replaces T-DM1” to “who exactly qualifies, and how do we safely deliver this in the curative setting?”

SABCS 2025 + NEJM publication (safety operationalization and practice consolidation)

Primary/KOL tweets:

• NEJM: Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer
• Dr. Yakup Ergun: DESTINY-Breast05 Publication Summary
• Dr. Hope Rugo Compares the Conclusion Slides of DESTINY-Breast05 and DESTINY-Breast11 with a focus on ILD.
  

Interesting Tweet: US lack of participation in DESTINY-Breast05

• Tone: Consolidation with nuance—broad acceptance of efficacy, increased focus on ILD mitigation (including RT timing) and on generalizability/access questions.
• Shift: From conference headline to implementation science (RT sequencing, monitoring protocols, and defining the “high-risk residual disease” population precisely).

Overall, DESTINY-Breast05 discourse evolves from an ESMO 2025 efficacy shockwave to a SABCS/NEJM phase of operational refinement: how to select patients, how to manage ILD risk (including during RT), and how to integrate DB-05 into an increasingly complex perioperative HER2+ ecosystem that also includes neoadjuvant T-DXd strategies.

DESTINY-Breast05 Professional Resources