Randomized, Placebo-Controlled Study of Oregovomab for Consolidation of Clinical Remission in Patients With Advanced Ovarian Cancer

Berek, Jonathan S.; Taylor, Peyton T.; Gordon, Alan N.; Cunningham, Mary; Finkler, Neil J.; Orr, James W.; Rivkin, Saul E.; Schultes, Birgit C.; Whiteside, Theresa L.; Nicodemus, Christopher F.

doi:10.1200/jco.2004.09.016

Cited by 170 publications

(98 citation statements)

References 23 publications

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“…Four trials underestimated the actual outcome (A/E ratio of >1.25), Eleven trials were accurate (A/E ratio of 0.75‐1.25), and 5 trials overestimated the outcome (A/E ratio of 0.75) (Table 2). 12, 14, 17, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 The A/E ratios ranged from 0.5 to 1.6, with a mean and median ratio of 1.0 and 1.0, respectively (Fig. 3).…”

Section: Resultsmentioning

confidence: 98%

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Estimation of expectedness: Predictive accuracy of standard therapy outcomes in randomized phase 3 studies in epithelial ovarian cancer

Castonguay

Wilson

Díaz-Padilla

et al. 2014

Cancer

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BACKGROUNDThe anticipated clinical outcome of the standard/control arm is an important parameter in the design of randomized phase 3 (RP3) trials to properly calculate sample size, power, and study duration. Changing patterns of care or variation in the study population enrolled may lead to a deviation from the initially anticipated outcome. The authors hypothesized that recent changes in patterns of care in epithelial ovarian cancer (EOC) have led to challenges in correctly estimating the outcome of control groups.METHODSA systematic review of the literature was conducted for RP3 trials of EOC published between January 2000 and December 2010. The expected outcome of the control arm as well as the actual outcome achieved by this cohort was collected and a ratio (actual‐over‐expected ratio) was calculated. The estimation of outcome was deemed accurate if the outcome of the control arm was between 0.75 to 1.25 times the anticipated outcome.RESULTSA total of 35 trials were eligible for analysis. Fifteen trials had survival as the primary endpoint whereas 20 had a progression‐based primary endpoint. In total, 12 of 15 trials with a survival‐based endpoint significantly underestimated the outcome of the control arm, whereas only 4 of 20 trials with a progression‐based endpoint did. Studies with a survival endpoint underestimated outcome more frequently than those with a progression endpoint (P<.001).CONCLUSIONSSurvival of the control arm has frequently been underestimated in recent EOC RP3 trials. This underestimation means that the initial statistical assumptions of these trials may have been inaccurate. Underestimating the outcome of the control arm may result in trials being underpowered to demonstrate the absolute benefit they were designed to show. Cancer 2015;121:413–422. © 2014 American Cancer Society.

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Section: Resultsmentioning

confidence: 98%

“…A total of 3 and 7 studies were excluded from the OS15, 23, 29 and PFS17, 36, 38, 42, 43, 44, 45 analyses, respectively. This confirmed a statistically significant difference ( P = .001).…”

Section: Resultsmentioning

confidence: 99%

Estimation of expectedness: Predictive accuracy of standard therapy outcomes in randomized phase 3 studies in epithelial ovarian cancer

Castonguay

Wilson

Díaz-Padilla

et al. 2014

Cancer

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“…Further investigation of the immune response showed activation of both a humoral and a cellular CA 125 specific responses. A double-blind, placebo-controlled trial in which 145 epithelial ovarian cancer patients were treated with repeated iv B43.13 injections as consolidation therapy confirmed the induction of HAMA and Ab2 (37). However, the study did not demonstrate a prolonged time to relapse (TTR).…”

Section: Clinical Trialsmentioning

confidence: 95%

“…Because of the high propensity to stay confined to the peritoneal cavity until very late in the course of the disease, many trials on radiolabeled Mab in ovarian cancer patients used the ip route for administration (19/44) (38,41,44,50,51,63,64,(66)(67)(68)(69)(70)(71)(73)(74)(75)(76)(77)(78). In 20 studies the Mab was administered iv (36,37,39,40,42,43,45-49,52-55,57,60,65,72,79), two studies injected im (59,61), while 2 other studies used both iv and ip routes of administration Table I. Clinical trials in ovarian cancer with Mab directed towards antigen CA 125.…”

Section: Clinical Trialsmentioning

confidence: 99%

The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review)

Massuger¹,

Boerman²,

Thomas³

et al. 2008

Int J Oncol

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Abstract.The prognosis for patients with ovarian cancer is still poor and more effective therapeutic modalities are needed. (Radio)immunotherapy using monoclonal antibodies (Mabs) could be one of these approaches. Here, we review the status of (radio)immunotherapy using Mabs for the treatment of ovarian cancer. The Pubmed database was searched for clinical trials investigating the effect of (radio)immunotherapy in ovarian cancer published until October 1, 2007. Keywords for the search were: ovarian cancer, monoclonal antibodies, CA 125, gp38, HER2, HMFG, MUC1, TAG 72 and VEGF. A total of 44 trials on immunotherapy with unconjugated Mabs, Mab vaccination and (radio)immunotherapy directed towards the antigens CA 125, gp38, HER2, MUC1, TAG 72 or VEGF in patients with ovarian cancer were found, reviewed and discussed. Out of these trials, 23 studied immunotherapy with unconjugated Mabs, 5 vaccination with Mabs and 16 trials studied (radio)immunotherapy. The lack of large randomized prospective trials with Mabs directed to tumor-associated antigens expressed on ovarian cancer cells preclude any firm conclusion on the potential of Mabs use in the treatment of ovarian cancer. Oregovomab, directed against CA 125, and bevacizumab, targeting VEGF, are two unconjugated Mabs closest to clinical introduction for the treatment of ovarian cancer. Vaccination with Mab ACA 125 seems promising but these findings need to be confirmed in controlled randomized trials. Sole RIT should be investigated with the appropriate radionuclide and a Mab with high affinity for the specific tumor-associated antigen in the appropriate patient group to determine whether it may have a therapeutic effect. Additionally, appending (radio)immunotherapy with anti-TAG 72 or anti-MUC1 to other treatment strategies such as chemotherapy could also be a strategy worthwhile investigating. The potential of Mabs to complement current treatment paradigms, is encouraging and may bring a significant improvement to the overall therapeutic outcomes currently being achieved in ovarian cancer. IntroductionOvarian cancer is the fourth leading cause of cancer-related death in women, and accounts for the highest mortality rate of all gynecological malignancies (1). Its poor prognosis is mainly the result of the clinically occult nature of this disease. The peritoneal cavity in which the ovaries are localized provides a perfect environment for undisturbed subclinical growth. Furthermore, early detection is difficult because of the general asymptomatic presentation of the disease (2). In the majority (68%) of the patients, ovarian cancer is diagnosed with at least extensive abdominal spread (3). Standard treatment for advanced stage ovarian cancer is tumor debulking surgery and adjuvant chemotherapy. Although most ovarian cancers are sensitive to platinumbased chemotherapy, the prognosis remains poor. The 5-year INTERNATIONAL JOURNAL OF ONCOLOGY 32: 1145-1157 The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (Review) Abbreviations: ADCC, anti...

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“…Mab-B43.13, also called oregovomab, is a monoclonal antibody that binds to CA125 forming antigen-antibody complexes to stimulate an immune response [40,41]. Although patients had a measurable increase in both T and B cells [42,43], clinically it was met with limited success [44].…”

Section: Anti-muc16 Antibodiesmentioning

confidence: 99%

Targeting MUC16 in Cancer Therapy

Suh¹,

Valle²,

Morris³

2017

Chemotherapy (Los Angel)

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Over the recent decades, there has been a number of studies investigating the role of mucins in the pathogenesis of various cancers such as breast, lung, ovarian, gastrointestinal and pancreatic malignancies. Since then, it has been discovered that mucins play a critical role in tumorigenesis as they can mediate cell proliferation, metastasis and resistance to chemotherapy. Thus, mucins have been explored as a potential therapeutic target as well as a biomarker, as cancer cells often have an aberrant expression of mucins. MUC16 is a glycoprotein coded by one of the 21 mucin genes. CA125, the extracellular domain of MUC16, is a well-established biomarker for ovarian cancer, however there is no in depth literature review on MUC16 as a target for anti-cancer therapy. Thus, this review summarises the existing literature on MUC16, the current therapies targeting on MUC16 and highlights future avenues for targeting mucin-producing cancers.

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Randomized, Placebo-Controlled Study of Oregovomab for Consolidation of Clinical Remission in Patients With Advanced Ovarian Cancer

Abstract: Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment.

Cited by 170 publications

References 23 publications

Estimation of expectedness: Predictive accuracy of standard therapy outcomes in randomized phase 3 studies in epithelial ovarian cancer

Estimation of expectedness: Predictive accuracy of standard therapy outcomes in randomized phase 3 studies in epithelial ovarian cancer

The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review)

Targeting MUC16 in Cancer Therapy

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