BACKGROUND: This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials.gov (1966 to July 2009). We also conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For the first update of this review, we extended the searches to October 2013, and for this update, we extended the searches to July 2017. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), as well as non-randomised studies (NRSs), that included participants with epithelial ovarian cancer, irrespective of disease stage, who were treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, treatment schedule, and reported clinical or immunological outcomes. DATA COLLECTION AND ANALYSIS: Two reviews authors independently extracted the data. We evaluated the risk of bias for RCTs according to standard methodological procedures expected by Cochrane, and for NRSs by using a selection of quality domains deemed best applicable to the NRS. MAIN RESULTS: We included 67 studies (representing 3632 women with epithelial ovarian cancer). The most striking observations of this review address the lack of uniformity in conduct and reporting of early-phase immunotherapy studies. Response definitions show substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events is frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack the relevant information necessary for risk of bias assessment. Therefore, we cannot rule out serious biases in most of the included trials. However, selection, attrition, and selective reporting biases are likely to have affected the studies included in this review. GRADE ratings were high only for survival; for other primary outcomes, GRADE ratings were very low.The largest body of evidence is currently available for CA-125-targeted antibody therapy (17 studies, 2347 participants; very low-certainty evidence). Non-randomised studies of CA-125-targeted antibody therapy suggest improved survival among humoral and/or cellular responders, with only moderate adverse events. However, four large randomised placebo-controlled trials did not show any clinical benefit, despite induction of immune responses in approximately 60% of participants. Time to relapse with CA-125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9 months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty evidence). Only one RCT provided data on overall survival, reporting rates of 80% in both treatment and placebo groups (three RCTs, 1062 participants; high-certainty evidence). Other small studies targeting many different tumour antigens have presented promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results and the limited side effects and toxicity reported, exploration of clinical efficacy in large well-designed RCTs may be worthwhile. AUTHORS' CONCLUSIONS: We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously, as review authors found a significant dearth of relevant information for assessment of risk of bias in both RCTs and NRSs.
BACKGROUND: This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials.gov (1966 to July 2009). We also conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For the first update of this review, we extended the searches to October 2013, and for this update, we extended the searches to July 2017. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), as well as non-randomised studies (NRSs), that included participants with epithelial ovarian cancer, irrespective of disease stage, who were treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, treatment schedule, and reported clinical or immunological outcomes. DATA COLLECTION AND ANALYSIS: Two reviews authors independently extracted the data. We evaluated the risk of bias for RCTs according to standard methodological procedures expected by Cochrane, and for NRSs by using a selection of quality domains deemed best applicable to the NRS. MAIN RESULTS: We included 67 studies (representing 3632 women with epithelial ovarian cancer). The most striking observations of this review address the lack of uniformity in conduct and reporting of early-phase immunotherapy studies. Response definitions show substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events is frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack the relevant information necessary for risk of bias assessment. Therefore, we cannot rule out serious biases in most of the included trials. However, selection, attrition, and selective reporting biases are likely to have affected the studies included in this review. GRADE ratings were high only for survival; for other primary outcomes, GRADE ratings were very low.The largest body of evidence is currently available for CA-125-targeted antibody therapy (17 studies, 2347 participants; very low-certainty evidence). Non-randomised studies of CA-125-targeted antibody therapy suggest improved survival among humoral and/or cellular responders, with only moderate adverse events. However, four large randomised placebo-controlled trials did not show any clinical benefit, despite induction of immune responses in approximately 60% of participants. Time to relapse with CA-125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9 months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty evidence). Only one RCT provided data on overall survival, reporting rates of 80% in both treatment and placebo groups (three RCTs, 1062 participants; high-certainty evidence). Other small studies targeting many different tumour antigens have presented promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results and the limited side effects and toxicity reported, exploration of clinical efficacy in large well-designed RCTs may be worthwhile. AUTHORS' CONCLUSIONS: We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously, as review authors found a significant dearth of relevant information for assessment of risk of bias in both RCTs and NRSs.
Authors: Mahsa Mohebtash; Kwong-Yok Tsang; Ravi A Madan; Ngar-Yee Huen; Diane J Poole; Caroline Jochems; Jacquin Jones; Theresa Ferrara; Christopher R Heery; Philip M Arlen; Seth M Steinberg; Mary Pazdur; Myrna Rauckhorst; Elizabeth C Jones; William L Dahut; Jeffrey Schlom; James L Gulley Journal: Clin Cancer Res Date: 2011-11-08 Impact factor: 12.531
Authors: G D MacLean; M B Bowen-Yacyshyn; J Samuel; A Meikle; G Stuart; J Nation; S Poppema; M Jerry; R Koganty; T Wong Journal: J Immunother (1991) Date: 1992-05
Authors: Samuel D Bernal; Enrique T Ona; Aileen Riego-Javier; Romulo DE Villa; Gloria R Cristal-Luna; Josephine B Laguatan; Eunice R Batac; Oscar Q Canlas Journal: Oncol Lett Date: 2011-09-20 Impact factor: 2.967
Authors: Jonathan Oh; Minal Barve; Carolyn M Matthews; E Colin Koon; Thomas P Heffernan; Bruce Fine; Elizabeth Grosen; Melanie K Bergman; Evelyn L Fleming; Leslie R DeMars; Loyd West; Daniel L Spitz; Howard Goodman; Kenneth C Hancock; Gladice Wallraven; Padmasini Kumar; Ernest Bognar; Luisa Manning; Beena O Pappen; Ned Adams; Neil Senzer; John Nemunaitis Journal: Gynecol Oncol Date: 2016-09-24 Impact factor: 5.482
Authors: Scott J Antonia; Noweeda Mirza; Ingo Fricke; Alberto Chiappori; Patricia Thompson; Nicholas Williams; Gerold Bepler; George Simon; William Janssen; Ji-Hyun Lee; Kerstin Menander; Sunil Chada; Dmitry I Gabrilovich Journal: Clin Cancer Res Date: 2006-02-01 Impact factor: 12.531
Authors: Dan Laheru; Eric Lutz; James Burke; Barbara Biedrzycki; Sara Solt; Beth Onners; Irena Tartakovsky; John Nemunaitis; Dung Le; Elizabeth Sugar; Kristen Hege; Elizabeth Jaffee Journal: Clin Cancer Res Date: 2008-03-01 Impact factor: 12.531
Authors: M B Yacyshyn; S Poppema; A Berg; G D MacLean; M A Reddish; A Meikle; B M Longenecker Journal: Int J Cancer Date: 1995-05-16 Impact factor: 7.396
Authors: Neil L Berinstein; Mohan Karkada; Michael A Morse; John J Nemunaitis; Gurkamal Chatta; Howard Kaufman; Kunle Odunsi; Rita Nigam; Leeladhar Sammatur; Lisa D MacDonald; Genevieve M Weir; Marianne M Stanford; Marc Mansour Journal: J Transl Med Date: 2012-08-03 Impact factor: 5.531
Authors: Sarah Nersesian; Haley Glazebrook; Jay Toulany; Stephanie R Grantham; Jeanette E Boudreau Journal: Front Immunol Date: 2019-08-09 Impact factor: 7.561
Authors: Dmitriy Zamarin; Sven Walderich; Aliya Holland; Qin Zhou; Alexia E Iasonos; Jean M Torrisi; Taha Merghoub; Lewis F Chesebrough; Autumn S Mcdonnell; Jacqueline M Gallagher; Yanyun Li; Travis J Hollmann; Rachel N Grisham; Courtney L Erskine; Mathew S Block; Keith L Knutson; Roisin E O'Cearbhaill; Carol Aghajanian; Jason A Konner Journal: J Immunother Cancer Date: 2020-06 Impact factor: 13.751