Phase IIa Trial of Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive, Locally Advanced, or Metastatic Breast Cancer

Miller, Kathy D.; Dièras, Véronique; Harbeck, Nadia; Varga, Andrea; Mahtani, Reshma; Gianni, Luca; Albain, Kathy S.; Crivellari, Diana; Liang, Fang Ting; Michelson, Glenn; Haas, Sanne L. de; Burris, Howard A.

doi:10.1200/jco.2013.52.6590

Cited by 73 publications

(68 citation statements)

References 26 publications

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“…After exclusion of duplicate references, nonrelevant literature, and those that did not satisfy the inclusion criteria, 19 candidate articles were included. AHT was used for advanced breast cancer in eight studies [13][14][15][16][17][18][19][20], in eight studies in the neoadjuvant setting [21][22][23][24][25][26][27][28], in two adjuvant trials [29,30], and in one study in both metastatic and neoadjuvant disease [31]. Tables 1, 2, 3, 4, 5 and 6 outline the main study characterizes and the outcomes of the 19 included studies.…”

Section: Resultsmentioning

confidence: 99%

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The predictive and prognostic role of phosphatase phosphoinositol-3 (PI3) kinase (PIK3CA) mutation in HER2-positive breast cancer receiving HER2-targeted therapy: a meta-analysis

Ibrahim

Kazkaz

Al‐Μansour³

et al. 2015

Breast Cancer Res Treat

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The association between PIK3CA mutation and resistance to anti-HER2 therapy (AHT) is not precisely defined. This meta-analysis intended to explore the clinical utility of PIK3CA mutation in HER2-positive breast cancer treated with AHT. Literature search identified 19 eligible studies. There were 1720 patients with advanced, 828 with early and 1290 patients treated in the neoadjuvant setting. In metastatic breast cancer, AHT showed no differential objective response benefit between the wild type (WT) and the mutated type (MT) PIK3CA subgroups (odds ratio [OR] = 1.09; 95 % CI 0.60-2.00; P = 0.78). AHT favorable affected progression-free survival (PFS) irrespective of PIK3CA mutation. There was no PFS difference between WT and MT regardless of the offered therapy. In early breast cancer, trastuzumab combined with the same chemotherapy conferred consistent relapse-free survival benefit in WT and MT subgroups (WT: HR = 0.59; 95 % CI 0.44-0.80; P < 0.001 vs. MT: HR = 0.42; 95 % CI 0.24-0.74; P < 0.001). In the neoadjuvant setting, AHT-based therapy produced a 72 % higher pathologic complete response (pCR) rate in WT as compared with that in MT PIK3CA tumors (OR = 1.72; 95 % CI 1.29-2.13; P < 0.001). In that setting, there was no disease-free or overall survival difference based on PIK3CA mutational status. In this meta-analysis, AHT did not achieve differential benefit according to PIK3CA mutation in HER2-positive metastatic or early breast cancer; however, in the neoadjuvant setting, patients harboring WT PIK3CA tumors attained a higher pCR rate.

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Section: Resultsmentioning

confidence: 99%

“…When reported, most patients were above the age of 50 years, and the median follow-up ranges between 6.5 and 50 months. In seven studies, a single AHT was used [13-15, 17, 19, 20, 31], and in one study a dual agents were used [18]. The eight study randomized patients between dual agents and single agent [16].…”

Section: Studies In Metastatic Diseasementioning

confidence: 99%

The predictive and prognostic role of phosphatase phosphoinositol-3 (PI3) kinase (PIK3CA) mutation in HER2-positive breast cancer receiving HER2-targeted therapy: a meta-analysis

Ibrahim

Kazkaz

Al‐Μansour³

et al. 2015

Breast Cancer Res Treat

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“…Brentuximab vedotin, a CD30-targeted antimitotic agent, demonstrated an overall and progression-free survival of 40.5 and 9.3 months, respectively, in Hodgkin lymphoma patients (6). In a phase IIa clinical trial of ado-trastuzumab vedotin, a Her2-targeted taxane, the overall response rate was 33% in metastatic breast cancer patients previously treated with chemotherapy and 57% as first-line therapy with progression-free survival of 5.5 and 7.7 months, respectively (7). Thus, in clinical practice today, only two ADCs continue to demonstrate clinical efficacy, in the face of hundreds of tumor-specific mAbs and chemotherapy agents.…”

Section: Introductionmentioning

confidence: 99%

Antibody-Targeted Chemotherapy for the Treatment of Melanoma

et al. 2016

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Antibody-directed chemotherapy (ADC) offers an advantage over conventional chemotherapy because it provides antibodydirected targeting, with resultant improvement in therapeutic efficacy and reduced toxicity. Despite extensive research, with notable exceptions, broad clinical application of ADC remains elusive; major hurdles include the instability of antibodychemotherapy linkers and reduced tumor toxicity of the chemotherapy when bound to the antibody. To address these challenges, we have developed a platform technology that utilizes the nab-paclitaxel formulation of paclitaxel, Abraxane, in which hydrophobic paclitaxel is suspended in 130-nm albumin nanoparticles and thus made water-soluble. We have developed a method to noncovalently coat the Abraxane nanoparticle with recombinant mAbs (anti-VEGF, bevacizumab) and guide Abraxane delivery into tumors in a preclinical model of human A375 melanoma. Here, we define the binding characteristics of bevacizumab and Abraxane, demonstrate that the chemotherapy agent retains its cytotoxic effect, while the antibody maintains the ability to bind its ligand when the two are present in a single nanoparticle (AB160), and show that the nanoparticle yields improved antitumor efficacy in a preclinical human melanoma xenograft model. Further data suggest that numerous therapeutic monoclonal IgG1 antibodies may be utilized in this platform, which has implications for many solid and hematologic malignancies. Cancer Res; 76(13);

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“…ОО наблюдался у 57% больных, получавших лечение пер-вой линии, и у 33% в последующих линиях терапии. Ме-диана ВБП составила 7,7 мес на первой линии и 5,5 мес в последующих линиях лечения [45].…”

Section: дальнейшие исследования и перспективы применения трастузумабunclassified

A modern paradigm for treating HER2-positive advanced breast cancer: Dual HER2 blockade and antibody-drug conjugates

Борисов¹,

Сакаева²

2015

Onkol. Z. im. P.A. Gercena

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Phase IIa Trial of Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive, Locally Advanced, or Metastatic Breast Cancer

Abstract: T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the first-line and advanced MBC settings warrants further investigation.

Cited by 73 publications

References 26 publications

The predictive and prognostic role of phosphatase phosphoinositol-3 (PI3) kinase (PIK3CA) mutation in HER2-positive breast cancer receiving HER2-targeted therapy: a meta-analysis

The predictive and prognostic role of phosphatase phosphoinositol-3 (PI3) kinase (PIK3CA) mutation in HER2-positive breast cancer receiving HER2-targeted therapy: a meta-analysis

Antibody-Targeted Chemotherapy for the Treatment of Melanoma

A modern paradigm for treating HER2-positive advanced breast cancer: Dual HER2 blockade and antibody-drug conjugates

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