PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

Naumann, R. Wendel; Coleman, Robert L.; Burger, Robert A.; Sausville, Edward A.; Kutarska, E.; Ghamande, Sharad; Gabrail, Nashat; DePasquale, Stephen; Nowara, Elżbieta; Gilbert, Lucy; Gersh, Robert H.; Teneriello, Michael; Harb, Wael A.; Konstantinopoulos, Panagiotis A.; Penson, Richard T.; Symanowski, James T.; Lovejoy, C.; Leamon, Christopher P.; Morgenstern, David; Messmann, Richard A.

doi:10.1200/jco.2013.49.7685

Cited by 176 publications

(133 citation statements)

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“…Wholebody imaging using FR-radiolabeled conjugates can address this challenge by allowing noninvasive assessment of FR expression for multiple lesions and at different times (3,4,13). Additionally, FR imaging using radiolabeled conjugates leads to visualization of all functional FRs and not only FRa, a fact that is important because FR-targeted treatments need to be actively transported into the cell by functional FRs (of any isoform) (11).…”

Section: Fr Expression Assessmentmentioning

confidence: 99%

“…FR expression has been shown in varying levels in many epithelial tumors (3). Few nonmalignant tissues, such as epithelial cells in the kidney and placenta, show FR expression, as most cells use the reduced folate carrier for folate transport (4).…”

mentioning

confidence: 99%

“…Different treatments targeting the FR have been developed, such as farletuzumab, vintafolide, EC1456 (a folatetubulysin conjugate in phase 1 trials), and IMGN853 (an anti-FR antibody-maytansinoid conjugate in phase 1 trials) (8). Farletuzumab and vintafolide have shown clinical promise in phase 2 and 3 trials (3,9). Farletuzumab is an FRa-specific monoclonal antibody that can induce cell death through complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (9).…”

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confidence: 99%

“…Farletuzumab is an FRa-specific monoclonal antibody that can induce cell death through complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (9). Vintafolide can deliver chemotherapy to FR-expressing cells, as it is a conjugate of folate and the chemotherapeutic agent desacetylvinblastine monohydrazide (3).…”

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confidence: 99%

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Imaging the Folate Receptor on Cancer Cells with ^99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

et al. 2014

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Folate receptor (FR) can be used as a therapeutic target because of its expression on different epithelial cancers, such as ovarian, nonsmall cell lung, endometrial, and breast cancer. Assessing FR expression in tumors may help to identify patients who can benefit from FR-targeted therapeutics, such as vintafolide and farletuzumab. Different methods exist to detect FR expression. Tissue sampling has limited clinical utility, mainly because it requires an invasive procedure. 99m Tc-etarfolatide, a 99m Tc-labeled folate conjugate, is in latephase trials in Europe and the United States. It allows noninvasive, whole-body imaging of the FR. This review focuses on this FRimaging agent and how it may be used to direct FR-targeted therapy.

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Section: Fr Expression Assessmentmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Imaging the Folate Receptor on Cancer Cells with ^99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

et al. 2014

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“…Seven studies addressed systemic treatment in a platinum-sensitive population 10,11,15,23,31,41,44 . Twelve studies reported on patients with platinumresistant ovarian cancer 14,[17][18][19]24,30,36,[38][39][40]43,45 . …”

Section: Search For Existing Systematic Reviews and Primary Literaturementioning

confidence: 99%

Systemic Therapy for Recurrent Epithelial Ovarian Cancer: A Clinical Practice Guideline

et al. 2017

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Objective The purpose of this guideline is to recommend systemic therapy options for women with recurrent epithelial ovarian cancer, including fallopian tube and primary peritoneal cancers. Methods This document updates the recommendations published in the 2011 Optimal Chemotherapy forRecurrent Ovarian Cancer guideline from Cancer Care Ontario. Draft recommendations were formulated based on evidence obtained through a systematic review of phase ii and iii randomized controlled trials (rcts). The draft recommendations underwent internal review by clinical and methodology experts, and external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline. ResultsThe primary literature search yielded thirty-six primary research papers representing thirty rcts that met the eligibility criteria. The guideline provides recommendations for patients with serous tumour histologies and with recurrent, platinum-resistant, and platinum-sensitive ovarian cancer. ConclusionsThe body of evidence from trials that included olaparib and bevacizumab consistently shows a benefit in progression-free survival (pfs) without a corresponding benefit in overall survival (os). The Working Group for this guideline designated pfs, which is associated with symptom control, as a critical outcome. A finding of net benefit can therefore be concluded based on significant differences in pfs. However, that benefit is not without identified harms. Given the identified harms, patient involvement in the decision-making process must take into consideration the side effect profiles of olaparib and bevacizumab within the context of improved pfs but minimal change in os.

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Effect of Apatinib Plus Pegylated Liposomal Doxorubicin vs Pegylated Liposomal Doxorubicin Alone on Platinum-Resistant Recurrent Ovarian Cancer

et al. 2022

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IMPORTANCEThere are substantial unmet therapeutic needs in patients with platinum-resistant recurrent ovarian cancer (PROC), and novel therapeutic strategies should be explored.OBJECTIVE To evaluate the efficacy and safety of treatment with apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) plus pegylated liposomal doxorubicin (PLD) for PROC. DESIGN, SETTING, AND PARTICIPANTSThe APPROVE trial was performed as an open-label, randomized clinical trial at 11 hospitals in China between March 22, 2018, and November 16, 2020. Patients with histologically confirmed ovarian cancer who had experienced disease progression during or within 6 months of discontinuing any prior line of treatment with platinum-based chemotherapy were eligible. This primary analysis was based on data that were current as of January 28, 2021.INTERVENTIONS Patients received PLD alone (40 mg/m 2 , intravenously, every 4 weeks, for up to 6 cycles) or PLD plus apatinib (250 mg, orally, daily). MAIN OUTCOMES AND MEASURESThe primary end point was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, in the intent-to-treat population. RESULTSIn total, 152 female patients were randomized, with 78 (51.3%) in the apatinib plus PLD group (median age, 54 years; range, 22-76 years) and 74 (48.7%) in the PLD group (median age, 56 years; range, 33-72 years). The median follow-up duration was 8.7 months (IQR, 4.7-14.1 months). The median PFS was 5.8 months (95% CI, 3.8-8.8) for treatment with apatinib plus PLD vs 3.3 months (95% CI, 2.1-3.8) for PLD (hazard ratio, 0.44; 95% CI, 0.28-0.71; P < .001). The median overall survival was 23.0 months (95% CI, 18.9 to not reached) with treatment with apatinib plus PLD vs 14.4 months (95% CI, 12.1-23.4) with PLD (hazard ratio, 0.66; 95% CI, 0.40-1.09). The most frequent grade 3 or higher treatment-emergent adverse events were decreased neutrophil counts (11 [14.9%] in the apatinib plus PLD group vs 6 [8.3%] in the PLD group), hypertension (6 [8.1%] vs none), and decreased white blood cell count (5 [6.8%] vs 3 [4.2%]). Two patients receiving treatment with apatinib plus PLD experienced grade 2 fistulas.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that treatment with apatinib plus PLD showed promising efficacy and manageable toxic effects in patients with PROC and may be a new alternative treatment option in this setting.

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PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

Abstract: Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

Cited by 176 publications

References 16 publications

Imaging the Folate Receptor on Cancer Cells with ^99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

Imaging the Folate Receptor on Cancer Cells with ^99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

Systemic Therapy for Recurrent Epithelial Ovarian Cancer: A Clinical Practice Guideline

Effect of Apatinib Plus Pegylated Liposomal Doxorubicin vs Pegylated Liposomal Doxorubicin Alone on Platinum-Resistant Recurrent Ovarian Cancer

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PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

Abstract: Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

Cited by 176 publications

References 16 publications

Imaging the Folate Receptor on Cancer Cells with 99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

Imaging the Folate Receptor on Cancer Cells with 99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

Systemic Therapy for Recurrent Epithelial Ovarian Cancer: A Clinical Practice Guideline

Effect of Apatinib Plus Pegylated Liposomal Doxorubicin vs Pegylated Liposomal Doxorubicin Alone on Platinum-Resistant Recurrent Ovarian Cancer

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Imaging the Folate Receptor on Cancer Cells with ^99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

Imaging the Folate Receptor on Cancer Cells with ^99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging