

Breast cancer
Destiny Breast - 01 trial | 2020 | HER2+ advanced |
Destiny Breast - 04 | 2022 | HER2+ advanced |
Destiny Breast - 03 | 2022 | HER2+ advanced |
Tailor-X | 2018 | HER2+ perioperative |
Katherine Trial | 2020 | HER2+ perioperative Tx |
PALOMA-3 trial | 2016 | HR+ advanced (CDK 4/6 and PIC3CA) |
PALOMA-2 Trial | 2016 | HR+ advanced (CDK 4/6 and PIC3CA) |
MONARCH 2 trial | 2017 | HR+ advanced (CDK 4/6 and PIC3CA) |
MONARCH 3 trial | 2017 | HR+ advanced (CDK 4/6 and PIC3CA) |
MONALEESA-7 Trial | 2018 | HR+ advanced (CDK 4/6 and PIC3CA) |
MONALEESA-3 trial | 2018 | HR+ advanced (CDK 4/6 and PIC3CA) |
Solar-1 Trial | 2019 | HR+ advanced (CDK 4/6 and PIC3CA) |
MonarchE trial | 2020 | HR+ advanced (CDK 4/6 and PIC3CA) |
PALLAS trial | 2021 | HR+ advanced (CDK 4/6 and PIC3CA) |
ATAC trial | 2002 | HR+ endocrine |
IES trial | 2004 | HR+ endocrine |
ITA trial | 2005 | HR+ endocrine |
NSABP B-33 | 2008 | HR+ endocrine |
BIG 1-98 trial | 2009 | HR+ endocrine |
TEAM trial | 2011 | HR+ endocrine |
ABCG 8 trial | 2012 | HR+ endocrine |
ATLAS trial | 2013 | HR+ endocrine |
ATTOM trial | 2013 | HR+ endocrine |
NCIC CTG MA.27 trial | 2013 | HR+ endocrine |
TEXT trail | 2014 | HR+ endocrine |
Meta-analysis of AI vs TAM in early breast cancer | 2015 | HR+ endocrine |
SOFT trial | 2015 | HR+ endocrine |
MA-17R | 2016 | HR+ endocrine |
FACE trial | 2017 | HR+ endocrine |
IDEAL (BOOG 2006-05) trial | 2018 | HR+ endocrine |
SOLE trial | 2018 | HR+ endocrine |
ABCSG-16 trial (SALSA) trial | 2021 | HR+ endocrine |
NSABP B-06 trial | 2002 | Miscellaneous |
NSABP B-04 trial | 2002 | Miscellaneous |
IMpassion130 | 2021 | TNBC advanced |
ASCENT Trial | 2021 | TNBC advanced |
NSABP-B15 trial | 1990 | TNBC perioperative |
CALGB 9344 trial | 2003 | TNBC perioperative |
CALGB 9741 trial | 2003 | TNBC perioperative |
USORTC-9735 trial | 2009 | TNBC perioperative |
CALGB 40101 trial | 2012 | TNBC perioperative |
CALGB 40603 (Alliance) trial | 2015 | TNBC perioperative |
CREATE-X trial | 2017 | TNBC perioperative |
Keynote-522 | 2020 | TNBC perioperative |
OlympiA trial | 2021 | TNBC perioperative |
Destiny Breast - 01 trialĀ
Modi S, 2020, NEJM, PMID: 31825192
HER2+ advanced
Background. Phase II study that included 184 patients with HER-2 positive metastatic breast cancer who previously were treated with trastuzumab emtansine to evaluate dosage safety and efficacy of Trastuzumab Deruxtecan. Median number of previous lines of therapy for metastatic disease was 6 (range 2 to 27) and included trastuzumab emtansine (100%), trastuzumab (100%), pertuzumab (65.8%), and other anti-HER2 therapies (54.3%)
Treatment Arm: Trastuzumab Deruxtecan 5.4 mg/kg body weight
Primary Endpoint: ORR
Median follow up: 11.1mo
ORR: 60.9%, 95%CI 53.4-68.0
Median response duration: 14.8mo 95% CI, 13.8-16.9
mPFS: 16.4 mo with 95% CI, 12.7 to not reached
Adverse events: Most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). Importantly, interstitial lung disease was seen in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%).
Conclusions: Trastuzumab Deruxtecan has durable anti-tumor activity in pretreated HER-2 positive metastatic breast cancer patients with close monitoring of pulmonary function given risk of Interstitial lung disease.
Summarized by Pragnan Kancharla, MD
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Trastuzumab deruxtecan (Enhertu)
Mechanism:Targets HER-2 trastuzumab and a topoisomerase I inhibitor conjugate deruxtecan (a derivative of exatecan) very potent inhibitor of topo I, x10fold than SN38 (irinotecan).
Tox: cardiotoxicity>>↓LVEF, do baseline TTE, hold if EF<40% or drops >20%, myelosuppression, fatigue, infusion related reactions, pulmonary tox with cough, SOB, infiltrated similar >> ILD in ~9% of the patients.