166MO Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from BEGONIA, a phase Ib/II study

Schmid, Patrick; Jung, Kyung-Hae; Wysocki, Piotr J.; Jassem, Jacek; Ma, Cynthia; Fernandes, Renan; Huisden, Robert; Stewart, Ross; Vuković, Petra; Nunes, Ana T.; Nowecki, Zbigniew

doi:10.1016/j.annonc.2022.03.185

Cited by 46 publications

(32 citation statements)

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“…BEGONIA is a phase Ib/II multiarm trial investigating durvalumab in combination with multiple different agents, including Dato-DXd, in the first line setting for patients with metastatic TNBC. At a median follow-up of 3.9 months, initial results for the 27 patients receiving Dato-DXd plus durvalumab demonstrated an ORR of 74% (7% CR and 67% PR), warranting further enrollment and analysis in the expansion phase (32).TROPION-Breast01 is a phase III trial assessing Dato-DXd versus investigator's choice chemotherapy (capecitabine, gemcitabine, eribulin, or vinorelbine) in patients with pre-treated (one or two previous lines) HR+/HER2-negative metastatic disease. The primary outcomes are PFS and overall survival.…”

Section: Looking To the Futurementioning

confidence: 98%

Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer

Matusz‐Fisher¹,

Tan²

2022

Ann Transl Med

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Section: Looking To the Futurementioning

confidence: 98%

Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer

Matusz‐Fisher¹,

Tan²

2022

Ann Transl Med

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“…Additionally, another basket in the BEGONIA trial investigated the ADC datopotamab deruxtecan, which is a TROP2-directed ADC. Upon combination with durvalumab as first-line treatment for patients with mTNBC, an ORR of 79% was observed [ 39 ]. The phase II Saci-IO trial (NCT04468061) will evaluate the efficacy of SG in combination with pembrolizumab for mTNBC with PD-L1 negative disease [ 40 ], while the ASCENT-04 trial (NCT05382286) will evaluate the efficacy of this combination for PD-L1 positive mTNBC [ 41 ].…”

Section: Finding the Optimal Chemotherapy Backbone For Icbmentioning

confidence: 99%

Immunotherapy for Metastatic Triple Negative Breast Cancer: Current Paradigm and Future Approaches

Geurts

Kok

2023

Curr. Treat. Options in Oncol.

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Opinion statementIn approximately 15–20% of the patients diagnosed with breast cancer, it comprises the triple negative (TN) subtype, which until recently lacked targets for specific treatments and is known for its aggressive clinical behavior in patients with metastatic disease. TNBC is considered the most immunogenic breast cancer subtype due to higher levels of tumor infiltrating lymphocytes (TILs), tumor mutational burden and PD-L1 expression, providing a rationale for immunotherapy. The addition of pembrolizumab to chemotherapy as first-line treatment resulted in significantly improved PFS and OS for PD-L1 positive mTNBC, leading to FDA approval. However, response rate of ICB in unselected patients is low. Ongoing (pre)clinical trials aim to further optimize ICB efficacy and widen its application beyond PD-L1 positive breast tumors. Novel immunomodulatory approaches to induce a more inflamed tumor microenvironment include dual checkpoint blockade, bispecific antibodies, immunocytokines, adoptive cell therapies, oncolytic viruses, and cancer vaccines. Preclinical data for these novel strategies seems promising, but solid clinical data to further support its application for mTNBC is awaited. Biomarkers capturing the degree of immunogenicity such as but not limited to TILs, CD8 T cell levels, and IFNg signatures could support deciding which therapeutic strategy is most appropriate for which patient. Given 1) the accumulating therapy options for patients with metastatic disease and 2) the heterogeneity of mTNBC from inflamed to immune-desert tumors, the challenge is to work towards immunomodulatory strategies for specific subgroups of patients with TNBC to enable personalized (immuno)therapy for patients with metastatic disease.

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“…The most common AE observed was mild stomatitis (69%). 60,61 The preliminary analysis of the DAISY trial shows that T-DXd has meaningful clinical activity in HER2-positive, HER2-low, and HER2-zero patients with BC (mPFS, 11.1; 95% CI, 8.4-NR; 6.7 (4.6-8.5), 4.2 (2.1-6.9) months, respectively. 21 Other ADCs evaluated in HER2-low BC are SYD985 and RC48.…”

Section: Proposed Sequencing Of T-dxd and Rationalementioning

confidence: 99%

“…The preliminary analysis of phase 1b/2 BEGONIA trial (NCT03742102), which evaluates the combination of durvalumab (immunotherapy) and Dato‐DXd as a first‐line treatment option in advanced/metastatic TNBC shows the response in 74% of patients and responses were regardless of PDL‐1 expression. The most common AE observed was mild stomatitis (69%) 60,61 . The preliminary analysis of the DAISY trial shows that T‐DXd has meaningful clinical activity in HER2‐positive, HER2‐low, and HER2‐zero patients with BC (mPFS, 11.1; 95% CI, 8.4–NR; 6.7 (4.6–8.5), 4.2 (2.1–6.9) months, respectively 21 …”

Section: Proposed Sequencing Of T‐dxd and Rationalementioning

confidence: 99%

A review of treatment options in HER2‐low breast cancer and proposed treatment sequencing algorithm

Roy

Kumarasamy

Dhakal

et al. 2023

Cancer

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The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)‐status to HER2‐low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2‐low expression has emerged as a targetable biomarker, and anti‐HER2 antibody‐drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2‐low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor–positive and triple‐negative BC needs to be reconsidered, as approximately half of these BCs are HER2‐low. Although there are different therapeutic agents for hormone receptor–positive and hormone receptor–negative HER2‐low BCs, there is no consensus regarding the sequencing of these agents. In this article, the treatment options for HER2‐low BC are enumerated and a treatment sequencing algorithm based on the current clinical evidence proposed.

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166MO Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from BEGONIA, a phase Ib/II study

Cited by 46 publications

References 0 publications

Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer

Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer

Immunotherapy for Metastatic Triple Negative Breast Cancer: Current Paradigm and Future Approaches

A review of treatment options in HER2‐low breast cancer and proposed treatment sequencing algorithm

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