Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer

Verschraegen, Claire F.; Czok, S.; Muller, Carolyn Y.; Boyd, Leslie R.; Lee, S. J.; Rutledge, Teresa; Blank, Stephanie V.; Pothuri, Bhavana; Eberhardt, S.; Fm, Muggia

doi:10.1093/annonc/mds172

Cited by 45 publications

(21 citation statements)

References 26 publications

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“…The treatment combinations tested in this study were associated with acceptable toxicity profiles. Combining an antiangiogenic agent and chemotherapy has the potential risk of synergistic toxic effects [30,31]. In this study, toxicities were generally consistent with those that have been associated with monotherapy of trebananib, PLD, or topotecan [16,32,33].…”

Section: Discussionsupporting

confidence: 78%

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

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Schilder

Pippitt

et al. 2014

Gynecologic Oncology

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Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m 2 (cohorts A1 and A3, respectively) or topotecan 4 mg/m 2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.

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Section: Discussionsupporting

confidence: 78%

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

Vergote

Schilder

Pippitt

et al. 2014

Gynecologic Oncology

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“…In addition, combination therapy with PLD and bevacizumab shrank the recent recurrent tumor that had appeared following surgical resection and that had increased in size after the third‐line chemotherapy. Both PLD alone and PLD combined with bevacizumab have been effective for recurrent ovarian cancer, with some specific severe adverse effects . No case of HCO, however defined, treated with PLD and bevacizumab has been reported to date.…”

Section: Discussionmentioning

confidence: 99%

Recurrent ovarian undifferentiated carcinoma resembling hepatoid morphology treated with pegylated liposomal doxorubicin and bevacizumab

Ishiguro

Kashima

Yachida

et al. 2017

J of Obstet and Gynaecol

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Hepatoid carcinomas are undifferentiated epithelial carcinomas that are pathologically similar to hepatocellular carcinoma, but occur in a variety of organs. Hepatoid carcinomas, as strictly defined, typically produce α-fetoprotein. In addition, a standard effective chemotherapy regimen for hepatoid carcinoma has yet to be established. We present a case of advanced primary ovarian cancer that was pathologically similar to hepatoid carcinoma without staining for α-fetoprotein or hepatocyte paraffin 1. The primary ovarian, metastatic, and recurrent tumors shared similar pathological characteristics. Fourth-line chemotherapy with pegylated liposomal doxorubicin and bevacizumab was effective in treating the recurrent tumor, even though this disease had recurred three times.

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“…During the last 13 mo, the results of no less than 60 clinical trials of this type have been published in peer-reviewed scientific journals (Table 3). The largest fraction of these studies involved the VEGF-targeting mAb bevacizumab, which has been tested, most often in combination with conventional chemotherapy and/or targeted anticancer agents, in cohorts of patients affected by acute myeloid leukemia, 121 multiple myeloma, 122 head and neck squamous cell carcinoma (HNSCC), 123 , 124 breast carcinoma, 48 , 125 - 130 melanoma, 131 hepatocellular carcinoma, 132 - 136 pancreatic cancer, 137 ovarian carcinoma, 138 - 143 prostate cancer, 144 and several other advanced or metastatic solid tumors 145 - 154 . Moreover, 89 Zr-conjugated bevacizumab has been investigated as a means to visualize neoplastic lesions by positron emission tomography (PET) in women with primary breast carcinomas, which often secrete high levels of VEGF 155 .…”

Section: Update On Clinical Reportsmentioning

confidence: 99%

Trial Watch

et al. 2014

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In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct immunostimulatory effects. These three classes of mAbs exert antineoplastic activity via distinct mechanisms, which may or may not involve immune effectors other than the mAbs themselves. In previous issues of OncoImmunology, we provided a brief scientific background to the use of mAbs, all types confounded, in cancer therapy, and discussed the results of recent clinical trials investigating the safety and efficacy of this approach. Here, we focus on mAbs that primarily target malignant cells or their interactions with stromal components, as opposed to mAbs that mediate antineoplastic effects by activating the immune system. In particular, we discuss relevant clinical findings that have been published during the last 13 months as well as clinical trials that have been launched in the same period to investigate the therapeutic profile of hitherto investigational tumor-targeting mAbs.

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Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer

Cited by 45 publications

References 26 publications

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

Recurrent ovarian undifferentiated carcinoma resembling hepatoid morphology treated with pegylated liposomal doxorubicin and bevacizumab

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