Zie ook in gerelateerde artikelen.

Zie ook literatuurlijst niet-toxische middelen en weinig invasieve behandelingen specifiek bij borstkanker zoals opgesteld door arts-bioloog drs. Engelbert Valstar

12 juni 2024: Bron: ASCO 2024

Ook uit de resultaten van de DESTINY-Breast06-studie blijkt dat immuuntherapie met trastuzumab deruxtecan (Enhertu) een uitstekende behandeling te zijn voor vooraf met minimaal 1 of meerdere vormen van hormoonbehandelingen behandelde borstkankerpatiënten met uitgezaaide hormoongevoelige borstkanker met HER-2 lage expressie van minimaal 1. In vergelijking met chemotherapie naar keuze van de behandelend arts verbeterde de ziekteprogressievrije tijd aanzienlijk met 5 procent. 

De DESTINY-Breast06-studie deelde gerandomiseerd 436 patiënten in die trastuzumab deruxtecan kregen en 430 patiënten kregen chemotherapie die de keuze was van de behandelend arts. In de chemogroep kreeg 60 procent capecitabine, 24 procent nab-paclitaxel en 16 procent paclitaxel. Verder had 82% van de deelnemers HER2-lage tumoren en 18% HER2-ultralage tumoren. 

  • Het primaire doel van de DESTINY-Breast06-studie was de progressievrije overleving (PFS) en deze was met 13,2 maanden voor trastuzumab deruxtecan versus 8,1 maanden voor de chemo in het voordeel van trastuzumab deruxtecan (HR 0,62).
  • De overall overleving (OS) was nog niet bereikt, maar was in de HER2-lage expressie groep na 12 maanden 87,6 procent versus 81,7 procent (HR 0,83) en in de HER2-lage expressie en de HER2 met ultra lage expressie 87 versus 81,1 procent (HR 0,81).
  • De analyse van alleen de patiënten met HER2-ultralage expressie toonde vergelijkbare resultaten.
  • De responspercentages waren respectievelijk 57,3 procent versus 31,2 procent. 

Het abstract van de studie werd op ASCO 2024 gepresenteerd:

Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06).

Authors

Giuseppe Curigliano
Giuseppe Curigliano

University of Milan and European Institute of Oncology, IRCCS, Milan, Italy

Giuseppe Curigliano, Xichun Hu, Rebecca Alexandra Dent, Kan Yonemori, Carlos H. Barrios, Joyce O'Shaughnessy, Hans Wildiers, Qingyuan Zhang, Seock-Ah Im, Cristina Saura, Laura Biganzoli, Joohyuk Sohn, Christelle Levy, William Jacot, Natasha Begbie, Jun Ke, Gargi Surendra Patel, Aditya Bardia

Organizations

University of Milan and European Institute of Oncology, IRCCS, Milan, Italy, Fudan University Shanghai Cancer Center, Shanghai, China, Division of Medical Oncology, National Cancer Centre of Singapore, Singapore, Singapore, National Cancer Center Hospital, Tokyo, Japan, Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil, Baylor University Medical Center, Texas Oncology, The US Oncology Network, Dallas, TX, Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium, Harbin Medical University Cancer Hospital, Harbin, China, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea, Vall d’Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain, Department of Oncology, Santo Stefano Hospital, Azienda USL Toscana Centro, Prato, Italy, Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea, Republic of (South), Centre François Baclesse, Caen, France, Department of Medical Oncology, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France, Clinical Development, Late-Stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom, Biometrics Oncology, Late-Stage Development, Oncology R&D, AstraZeneca, Waltham, MA, University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA

Abstract Disclosures

Research Funding

This study is sponsored by AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201).

Background:T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC.Methods:Pts with HER2-low or -ultralow, HR+ mBC were randomized 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety.Results:As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P<0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC.Conclusions:T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC. Clinical trial information: NCT04494425.

T-DXd,
HER2-low

(n=359)*
TPC,

HER2-low

(n=354)*
T-DXd,

ITT

(n=436)
TPC,

ITT

(n=430)
T-DXd,
HER2-ultralow

(n=76)
TPC,

HER2-ultralow

(n=76)
mPFS
(95% CI), mo¤
13.2
(11.4, 15.2)
8.1
(7.0, 9.0)
13.2
(12.0, 15.2)
8.1
(7.0, 9.0)
13.2
(9.8, 17.3)
8.3
(5.8, 15.2)
PFS HR
(95% CI),
P value
0.62
(0.51, 0.74),

<0.0001
0.63
(0.53, 0.75), <0.0001
0.78
(0.50, 1.21)
12-mo
OS rate, %
87.6 81.7 87.0 81.1 84.0 78.7
OS HR
(95% CI),
P value§
0.83
(0.66, 1.05),

0.1181
0.81
(0.65, 1.00)
0.75
(0.43, 1.29)
Confirmed
ORR, %¤
56.5
(51.2, 61.7)
32.2
(27.4, 37.3)
57.3
(52.5, 62.0)
31.2
(26.8, 35.8)
61.8
(50.0, 72.8)
26.3
(16.9, 37.7)

*HER2-low status investigator assigned;

subgroup analysis; HER2-ultralow status centrally confirmed;

¤by BICR;

§data immature.

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

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