Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts.

Iwata, Hiroji; Tamura, Kenji; Doi, Toshihiko; Tsurutani, Junji; Modi, Shanu; Park, Haeseong; Krop, Ian E.; Sagara, Yasuaki; Redfern, Charles H.; Murthy, Rashmi Krishna; Redman, Rebecca; Shitara, Kohei; Fujisaki, Yoshihiko; Sugihara, Masahiro; Zhang, Lin; Shahidi, Javad; Yver, Antoine; Takahashi, Shunji

doi:10.1200/jco.2018.36.15_suppl.2501

Cited by 85 publications

(68 citation statements)

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“…44). However, cases of fatal pneumonitis have also been reported (44), highlighting that greater efficacy in HER2-low cells may have a safety trade-off. Studies are ongoing to better define the efficacy as well as safety of DS-8201a.…”

Section: Mechanisms Of Intrinsic and Acquired Resistance To Her2-targmentioning

confidence: 99%

“…Many other HER2immunotherapy combinations are ongoing ( Supplementary Table S3). There is also great interest in combinations of HER2 antibody-drug conjugates and immunotherapy, as antibodydrug conjugates elicit immune responses and have enhanced efficacy in combination with checkpoint inhibitors preclinically (44). In addition, bispecifics are being explored targeting HER2 and immune components.…”

Section: Her2-targeted Immunotherapymentioning

confidence: 99%

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Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer

Meric‐Bernstam

Johnson

Dumbrava

et al. 2019

Clinical Cancer Research

253

177

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The introduction of HER2-targeted therapy for breast and gastric patients with ERBB2 (HER2) amplification/overexpression has led to dramatic improvements in oncologic outcomes. In the past 20 years, five HER2-targeted therapies have been FDA approved, with four approved in the past 8 years. HER2-targeted therapy similarly was found to improve outcomes in HER2-positive gastric cancer. Over the past decade, with the introduction of next-generation sequencing into clinical practice, our understanding of HER2 biology has dramatically improved. We have recognized that HER2 amplification is not limited to breast and gastric cancer but is also found in a variety of tumor types such as colon cancer, bladder cancer, and biliary cancer. Furthermore, HER2-targeted therapy has signal of activity in several tumor types. In addition to HER2 amplification and overexpression, there is also increased recognition of activating HER2 mutations and their potential therapeutic relevance. Furthermore, there is a rapidly growing number of new therapeutics targeting HER2 including smallmolecule inhibitors, antibody-drug conjugates, and bispecific antibodies. Taken together, an increasing number of patients are likely to benefit from approved and emerging HER2targeted therapies.

show abstract

Section: Mechanisms Of Intrinsic and Acquired Resistance To Her2-targmentioning

confidence: 99%

Section: Her2-targeted Immunotherapymentioning

confidence: 99%

Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer

Meric‐Bernstam

Johnson

Dumbrava

et al. 2019

Clinical Cancer Research

253

177

View full text Add to dashboard Cite

show abstract

“…The RR was 43%, with a disease control rate of 80%. The median PFS was 5.6 months . The DESTINY‐Gastric 01 study (NCT03329690) is an East Asian phase 2 study evaluating DS‐8201a versus physician’s‐choice chemotherapy in patients with HER2‐expressing, advanced gastric/GEJ adenocarcinoma who have received 2 prior therapies.…”

Section: Treatment Of Metastatic Diseasementioning

confidence: 99%

Optimal management of gastroesophageal junction cancer

Greally

Agarwal

Ilson

2019

Cancer

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Although recent decades have witnessed incremental improvements in the treatment of gastroesophageal junction (GEJ) carcinoma, outcomes remain modest. For locally advanced esophageal cancer, the addition of chemotherapy and/or radiation to surgery is considered the standard of care. Chemotherapy remains the primary treatment for metastatic disease and improves survival over best supportive care. However, the prognosis for patients with GEJ cancers, which are treated along the same paradigms as esophageal and gastric carcinomas, remain poor because of the emergence of chemoresistance and limited targeted therapeutic approaches, which include agents that target the HER2 and vascular endothelial growth factor pathways. Evaluation of immune checkpoint inhibitors in the chemorefractory setting have confirmed the activity of immunotherapy in esophagogastric cancer. Ongoing immunotherapeutic strategies are being evaluated in both the locally advanced and metastatic settings. This review focuses on the treatment of locally advanced and metastatic GEJ carcinomas, which encompass all tumors that have an epicenter within 5 cm proximal or distal to the anatomical Z‐line (Siewert classification). Because the vast majority of GEJ tumors are adenocarcinoma, the management of adenocarcinoma is the focus of this review. Evolving approaches and areas of clinical equipoise are discussed.

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“…Dem Molekül wird zugeschrieben, auch bei Patientinnen mit niedriger HER2-Expression eine Wirk-samkeit zu haben. Dies konnte auch in einer sehr großen Phase-I-Studie gezeigt werden [47]. Allerdings kam es bei knapp über 240 behandelten Patientinnen zu einem mit einer Pneumonitis assoziierten Todesfall.…”

Section: Therapie Des Metastasierten Her2-positiven Mammakarzinomsunclassified

Update Mammakarzinom 2019 Teil 2 – Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis

et al. 2019

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ZusammenfassungDie Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom hat sich in den letzten Jahren weiterentwickelt. Zusätzlich zum Therapiefortschritt in den etablierten Subgruppen (Hormonrezeptor- und HER2-Status) gibt es nun Therapien, die sich an einzelnen molekularen Charakteristika orientieren, wie zum Beispiel die PARP-Inhibitor-Therapie bei BRCA-mutierten Patientinnen. Zusätzlich dazu sind Tests in der Entwicklung, die innerhalb von Subgruppen weitere Marker etablieren sollen, um die Wirksamkeit einer Therapie vorherzusagen. Die PI3K-Mutationstestung bei HER2-negativen, hormonrezeptorpositiven Tumoren und die PD‑L1-Testung von Immunzellen bei triple-negativen Tumoren werden voraussichtlich in der klinischen Praxis etabliert, um Patientinnen für die jeweiligen Therapien auszuwählen. Mit neuen Therapieansätzen treten auch neue Nebenwirkungen auf. Das Management dieser Nebenwirkungen ebenso wie die der klassischen Therapien (supportive Therapie) ist mit der Einführung neuer Behandlungen essenziell, um die Lebensqualität der Patientinnen zu erhalten. Das Wissen über Maßnahmen zur Erhaltung und Verbesserung der Lebensqualität hat in den letzten Jahren deutlich zugenommen. Lifestyle-Faktoren sollten dabei ebenso Berücksichtigung finden wie moderne Therapieverfahren. Diese Übersichtsarbeit fasst die neuesten Studien und Veröffentlichungen zusammen und bewertet sie in Bezug auf die Relevanz für die klinische Praxis.

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Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts.

Cited by 85 publications

References 0 publications

Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer

Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer

Optimal management of gastroesophageal junction cancer

Update Mammakarzinom 2019 Teil 2 – Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis

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