27 november 2025: Bron: ESMO 2025, Astrazeneca

De resultaten uit de gerandomiseerde fase III TROPION-Breast02-studie laten uitstekende resultaten zien voor een eerstelijns behandeling met datopotamab deruxtecan (Datroway) bij patiënten met een lokaal recidief van inoperabele of uitgezaaide triple-negatieve borstkanker voor wie immuuntherapie geen optie was. In vergelijking met chemotherapie naar keuze van de behandelend oncoloog was de mediane overall overleving 5 maanden langer 23,7 maanden versus 18,7 maanden. En de mediane ziektevrije tijd verdubbelde met datopotamab deruxtecan (Datroway) van 5,6 maanden naar 10,8 maanden.

De conclusie van de onderzoekers zoals beschreven in het abstract is dan ook dat een eerstelijns behandeling met Datroway - datopotamab deruxtecan een statistisch significante en klinisch relevante verbetering geeft in overall overleving (OS) en ziektevrije overleving (PFS) ten opzichte van chemotherapie bij patiënten met lokaal recidiverende inoperabele of uitgezaaide triple-negatieve borstkanker voor wie immuuntherapie geen optie was om uiteenlopende redenen. Het veiligheidsprofiel van Datroway - datopotamab deruxtecan was beheersbaar. De resultaten ondersteunen datopotamab deruxtecan (Datrowayals de nieuwe eerstelijns standaardzorg voor deze groep van borstkankerpatiënten.

Op de website van Astrazeneca, de producent, staat dit persbericht met meer gegevens over de resultaten dan in het abstract van ESMO 2025: 

Datroway demonstrated an unprecedented median overall survival improvement of five months vs. chemotherapy as 1st-line treatment for patients with metastatic triple-negative breast cancer for whom immunotherapy was not an option in TROPION-Breast02

Datroway - datopotamab deruxtecan demonstrated a 5.0-month improvement in median OS compared to chemotherapy (hazard ratio 0.79; 95% confidence interval 0.64-0.98; p=0.0291). Median OS was 23.7 months for patients treated with Datroway versus 18.7 months for those treated with chemotherapy.

Datroway reduced the risk of disease progression or death by 43% compared to chemotherapy (HR 0.57; 95% CI 0.47-0.69; p<0.0001) as assessed by blinded independent central review (BICR). Median PFS was 10.8 months for patients treated with Datroway versus 5.6 months for those treated with chemotherapy.

In addition to patients whose tumours did not express PD-L1, TROPION-Breast02 enrolled patients with PD-L1 expressing tumours for whom immunotherapy was not an option due to other factors.

Summary of efficacy results



Datroway (n=323)

ICC (n=321)

Median OS, months (95% CI)

23.7 (19.8-25.6)

18.7 (16.0-21.8)

HR (95% CI)

0.79 (0.64-0.98)

p-value

0.0291

Median PFS by BICR, months (95% CI)

10.8 (8.6-13.0)

5.6 (5.0-7.0)

HR (95% CI)

0.57 (0.47-0.69)

p-value

<0.0001

Median PFS by investigator, months (95% CI)

9.6 (7.4-11.2)

5.2 (4.2-5.6)

HR (95% CI)

0.56 (0.47-0.67)

Confirmed ORR, %

62.5

29.3

CR, % (n)

9.0 (29)

2.5 (8)

PR, % (n)

53.6 (173)

26.8 (86)

Median DoR, months (95% CI)

12.3 (9.1-15.9)

7.1 (5.6-8.9)

As of 25 August 2025, data cut-off, 45 patients (14%) remained on Datroway and 8 patients (3%) on chemotherapy.
BICR, blinded independent central review; CI, confidence interval; CR, complete response; DoR, duration of response; HR, hazard ratio; ICC, investigator’s choice of chemotherapy; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response

Patients receiving Datroway were on treatment more than twice as long as those receiving chemotherapy (median duration of treatment of 8.5 versus 4.1 months) and experienced a lower rate of treatment-related adverse events (TRAEs) associated with discontinuation (4% versus 7%). Grade 3 or higher TRAEs occurred in 33% and 29% of patients in the Datroway and chemotherapy arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (3%, 13%), stomatitis (8%, 0%), leukopenia (<1%, 4%), fatigue (3%, 3%), vomiting (1%, <1%), anaemia (2%, 3%), alopecia (0%, <1%), peripheral neuropathy (0%, 2%), dry eye (1%, 0%), nausea (<1%, <1%), decreased appetite (<1%, <1%) and constipation (<1%, 0%). There was one Grade 5 interstitial lung disease (ILD) event in the Datroway arm adjudicated as drug-related by an independent committee. This event was characterised as Grade 3 pneumonitis and cause of death was attributed to disease progression by the treating investigator.


En hier het abstract zoals gepresenteerd op ESMO 2025:

LBA21 - First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase III TROPION-Breast02 trial

Speakers
  • Rebecca A. Dent (Singapore, Singapore)
Authors
  • Rebecca A. Dent (Singapore, Singapore)
  •  
  • Zhimin Shao (Shanghai, China)
  •  
  • Peter Schmid (London, United Kingdom)
  •  
  • Javier C. Cortés (Barcelona, Spain)
  •  
  • David W. Cescon (Toronto, Canada)
  •  
  • Shigehira Saji (Fukushima, Japan)
  •  
  • Kyung H. Jung (Seoul, Republic of Korea)
  •  
  • Thomas Bachelot (Lyon, France)
  •  
  • Shouman Wang (Changsha, China)
  •  
  • Gul Basaran (Istanbul, Türkiye)
  •  
  • Yee Soo Chae (Kyungpook, Republic of Korea)
  •  
  • Rofhiwa M. Mathiba (Johannesburg, South Africa)
  •  
  • Shin Cheh Chen (Taipei City, Taiwan)
  •  
  • Agostina Stradella (Hospitalet de Llobregat, Spain)
  •  
  • Nicola Battelli (Macerata, Italy)
  •  
  • Naoki Niikura (Kanagawa, Japan)
  •  
  • Kechen Zhao (Bothell, United States of America)
  •  
  • Petra Vukovic (Cambridge, United Kingdom)
  •  
  • Micah J. Maxwell (Gaithersburg, United States of America)
  •  
  • Tiffany A. Traina (New York, United States of America, NY)
Room
Munich Auditorium - CityCube B
Date
Sun, 19.10.2025
Time
08:30 - 10:00
Lecture Time
09:25 - 09:35

Background

Treatment (tx) options are limited and prognosis is poor for the ~70% of patients (pts) with locally recurrent inoperable or mTNBC for whom immunotherapy is not an option; moreover, approximately half of pts with mTNBC do not receive tx beyond 1L. Here, we report the primary analysis from the TROPION-Breast02 study (NCT05374512).

Methods

Adult pts with previously untreated locally recurrent inoperable or mTNBC, for whom immunotherapy was not an option, were randomised 1:1 to Dato-DXd (6 mg/kg IV Q3W) or investigator’s choice of chemotherapy (ICC; -paclitaxel/ capecitabine/ eribulin mesylate/ carboplatin). Randomisation was stratified by geographic location, PD-L1 status and disease-free interval history (de novo vs DFI 0–12 months vs DFI >12 months; DFI defined as time from completion of tx with curative intent to first documented local/distant disease recurrence). Dual primary endpoints were OS and PFS by BICR per RECIST 1.1.

Results

644 pts were randomised (Dato-DXd: 323; ICC: 321). At data cutoff (25 Aug 2025), median study follow-up was 27.5 months. Results are shown in the Table. There was a statistically significant, ≥5 mo improvement in both median OS and PFS by BICR with Dato-DXd compared with ICC; OS HR 0.79 [95% CI 0.64‒0.98]; p=0.0291, and PFS HR 0.57 [95% CI 0.47‒0.69]; p<0.0001. Despite more than double the duration of tx in the Dato-DXd arm, rates of grade ≥3 TRAEs were similar and discontinuations were lower vs ICC.

Dato-DXd ICC
Efficacy N=323 N=321
OS
Median OS, mo (95% CI) 23.7 (19.8‒25.6) 18.7 (16.0‒21.8)
HR (95% CI) 0.79 (0.64‒0.98); p=0.0291
PFS (BICR)
Median PFS, mo (95% CI) 10.8 (8.6‒13.0) 5.6 (5.0‒7.0)
HR (95% CI) 0.57 (0.47‒0.69); p<0.0001
Response
Confirmed objective response rate (BICR), n (%) 202 (62.5) 94 (29.3)
Median duration of response, mo (95% CI) 12.3 (9.1–15.9) 7.1 (5.6–8.9)
Safety N=319 N=309
Median duration of tx, mo (range) 8.5 (0.7–38.0) 4.1 (0.1–32.0)
TRAEs, %
Any grade 92.8 83.2
Grade ≥3 32.9 28.8
Leading to discontinuation 4.4 7.4
Leading to death 0 0
BICR, blinded independent central review; OS, overall survival; PFS, progression-free survival; TRAEs, tx-related adverse events.

Conclusions

TROPION-Breast02 met both dual primary endpoints; 1L Dato-DXd demonstrated statistically significant and clinically meaningful OS and PFS improvement over chemotherapy in pts with locally recurrent inoperable or mTNBC for whom immunotherapy was not an option. The Dato-DXd safety profile was manageable. Results support Dato-DXd as the new 1L standard of care.

Clinical trial identification

NCT05374512; release date 16 May 2022.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), an Inizio company, in accordance with Good Publication Practice (GPP) guidelines, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

This trial is sponsored by AstraZeneca. In July 2020, Daiichi Sankyo entered into a global development and commercialisation collaboration with AstraZeneca for datopotamab deruxtecan (Dato-DXd).

Disclosure

R.A. Dent: Financial Interests, Personal, Advisory Role, Consulting/Advisory Role: AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/Astra Zeneca, Roche, Gilead Sciences; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/Astra Zeneca, Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/Astra Zeneca, Roche, Gilead Sciences, DKSH; Financial Interests, Institutional, Research Funding: AstraZeneca, Roche. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Pfizer, Roche, Gilead, Daiichi Sankyo, MSD, Bicycle Therapeutics, Lilly, Summit Therapeutics, Olema Oncology; Financial Interests, Personal, Invited Speaker: Menarini-Stemline, Gilead, AstraZeneca, Daiichi Sankyo, MSD, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Genentech, Roche. J.C. Cortés: Financial Interests, Personal, Advisory Board, consulting/advisor: Roche, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Lilly, MERCK SHARP& DOHME, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, Abbvie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech, Circle Pharma, Delcath Systems, Hexagon Bio; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eisai, Pfizer, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo, Astrazeneca, Gilead, Steamline Therapeutics, Zuellig Pharma; Financial Interests, Personal, Advisory Board: Bliss Biopharmaceutical; Financial Interests, Personal, Ownership Interest: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, Astrazeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Queen Mary University of London, Iqvia; Other, Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, Astrazeneca, Steamline Therapeutics; Other, Other, travel cost and expenses: Merck Sharp&Dhome. D.W. Cescon: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Exact Science, GenomeRx, Gilead, Lilly, Merck, Novartis, Pfizer, Roche, SAGA; Financial Interests, Institutional, Funding, Research funding (non-clinical), Local PI, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Research Grant: GenomeRx, ProteinQure; Financial Interests, Institutional, Local PI: Gilead, Pfizer; Financial Interests, Institutional, Funding, Research Funding, Local PI and Steering Committee Member: GSK; Financial Interests, Institutional, Funding, Research: Grail; Financial Interests, Institutional, Other, Collaborative Research Agreement: Guardant Health; Financial Interests, Institutional, Other, Research funding and in-kind support: Inivata/NeoGenomics; Financial Interests, Institutional, Other, In kind support of research: Knight Therapeutics; Financial Interests, Institutional, Funding, Local PI and Steering Committee Member: Merck; Non-Financial Interests, Advisory Role: Canadian Breast Cancer Network. S. Saji: Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai, Astra Zeneca, Kyowa Kirin, Daiichi Sankyo, Taiho, Pfizer, MSD, Novartis, Eisai, Ono, Takeda, Exact Sciences; Financial Interests, Personal, Advisory Board: Gilead, Myriad Genetics; Financial Interests, Institutional, Research Grant: Taiho, Chugai, Daiichi Sankyo; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, Chugai, Astra Zeneca, Sanofi, Gilead, Eli Lilly, Jazz Pharmaceuticals; Financial Interests, Personal, Steering Committee Member: Jazz Pharmaceuticals, Daiichi Sankyo, AstraZeneca; Non-Financial Interests, Member of Board of Directors: Japanese Breast Cancer Society, Japanse Society of Medical Oncology, Japan Breast Cancer Research Group. K.H. Jung: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Gilead Sciences, Daewong Pharmaceutical, Eisai, Pfizer, MSD; Other, Other, Support for third-party writing assistance: Roche, AstraZeneca. T. Bachelot: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, SeaGen, Daiichi Sankyo, Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, SeaGen, Pfizer; Financial Interests, Personal, Steering Committee Member: Roche; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca. A. Stradella: Financial Interests, Personal, Speaker’s Bureau: Daiichi, Novartis and Astra Zeneca; Financial Interests, Personal, Other, Travel, accommodations or expenses: Eisai, Novartis, Pfizer and MSD; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Seagen and Gilead. N. Battelli: Financial Interests, Personal, Invited Speaker, Invited as breast cancer expert: AstraZeneca, Daiichi Sankyo, Eli Lilly, Genetic, Menarini, Novartis, Pfizer, Roche. N. Niikura: Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co., Pfizer, Eisai, Mochida, Daiichi Sankyo, and Novartis; Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical Co., Pfizer, Eli Lilly, MSD, Daiichi Sankyo and AstraZeneca. K. Zhao: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P. Vuković: Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M.J. Maxwell: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. T.A. Traina: Financial Interests, Personal, Advisory Role: AstraZeneca, bioTheranos, Daiichi Sankyo, Exact Sciences, GE Healthcare, Genentech/Roche, Gilead Sciences, GSK, G1 Therapeutics, Hengrui Pharmaceutical, Merck, Novartis, Stemline Therapeutics and TerSera Therapeutics; Financial Interests, Personal, Research Funding: Astellas, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech/Roche and Pfizer. All other authors have declared no conflicts of interest.





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