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Objective: There are no data, and thus no consensus, on the optimal duration of poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy for exceptional responders (here defined as progression-free for 5 years or longer) with platinum sensitive recurrent ovarian cancer. The current licence is to continue PARP inhibitors until progression or toxicity; however, international practice varies considerably. The risks of late progression and late-onset myeloid malignancies, defined as occurring beyond 5 years of PARP inhibition, are unknown. This study aims to examine the practice patterns and opinions regarding the management and surveillance protocols of exceptional responders with platinum sensitive recurrent ovarian cancer., Methods: An online international survey of experts from June 2023 to June 2024 was carried out, disseminated at Gynaecologic Cancer Intergroup meetings and by Chairs of Cooperative Groups., Results: 210 responses were received from 26 countries including Australia (27 respondents), Germany (24), the UK (21), the Netherlands (16), France (13), Spain (12), Canada (12), Italy (11), Japan (11), and other countries (63). Most respondents did not have institutional or trials group guidelines regarding duration of PARP inhibitors (154, 73.3%). For the minority with guidelines, recommendations varied: 1 year (2), 2 years (13), 3 years (4), and indefinite treatment (22). Individual practice varied considerably for those without guidelines: most (116, 76.3%) recommended ≥5 years of PARP inhibition, of which 73 (48.0%) recommended indefinite PARP inhibition. Sixty-six respondents (31.4%) reported having patients with late progression and 46 (22.0%) had cases with late-onset myeloid malignancies. Surveillance practices varied widely across all respondents., Conclusions: This international survey highlights the diverse practice variations and disparate views on the optimal duration of maintenance therapy with PARP inhibitors in platinum sensitive recurrent ovarian cancer. The responses suggest a notable risk of late progression and myelodysplastic syndrome/acute myeloid leukemia among exceptional responders which needs confirmation. Detailed individual patient data is required to draw more reliable conclusions; another study is underway addressing this., Competing Interests: Competing interests: The authors have the following relevant disclosures within the last 36 months: AGM: honoraria from AstraZeneca, GlaxoSmithKline, Clovis, Roche, Novocure, MSD, Takeda, Zaylab; travel support from AstraZeneca, GSK and MSD; participation on a Data Safety Monitoring Board or Advisory Board for Alkermes, AstraZeneca, Amgen, Clovis, Eisai, GlaxoSmithKline, Immunogen, GenMab, Kartos, Sutro, Roche, Sotio, Macrogenics, Mersana, MSD, Pharmamar, Novartis, Oncoinvent, Regeneron, HederaDx, Illumina, Tubulis, Daiichi Sakyo, Incyte, Novocure, BionTech and other institutional financial or non-financial interests from GSK and Roche. AL: institutional funding from GSK, MSD, AstraZeneca, Immunogen, Owkin, Oseimmuno, Incyte, Adaptimmune, Eisai, Zentalis; consulting fees from MSD, GSK, AstraZeneca, Zentalis, Apmonia, Daiichi, Owkin, Immunogen, Incite, Genmab (payments for these to institution); honoraria from GSK, MSD, AstraZeneca and Servier; travel support from Oseimmuno, AstraZeneca and GSK; participation on a Data Safety Monitoring Board or Advisory Board for Pfizer; leadership role in GINECO; member of strategic committee in GCIG, ENGOT member and ESMO track chair/faculty. AO: grants from AstraZeneca and Amgen; consulting fees from BMS; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca and GSK, Steering Committee for AstraZeneca and GSK; and Principal Investigator of investigator initiated trials for AstraZeneca and GSK. AT: honoraria from GSK and AstraZeneca; travel support from GSK. CM: funded research: EU, FWF, AstraZeneca, Roche; honoraria/expenses from Roche, Novartis, MSD, Pharmamar, AstraZeneca, GSK and Consulting/Advisory Board for Roche, Novartis, MSD, AstraZeneca, Pfizer, Pharmamar, ImmunoGen, Daiichi Sankyo, Biontech, Novocure, Eisai, GSK, Abbvie, and Seagen. CG: manuscript support, grants, and contracts from AstraZeneca, GlaxoSmithKline, Tesaro, Clovis, MSD, BergenBio, Novartis, Aprea, Artios, Verastem, Roche, and Medannex; consulting fees from AstraZeneca, MSD, GlaxoSmithKline, and Verastem; honoraria for lectures and presentations from AstraZeneca, MSD, GlaxoSmithKline, Tesaro, Clovis, Roche, Nucana, Chugai, Takeda, Cor2Ed, and Peervoice; advisory board attendance from AstraZeneca, MSD, GlaxoSmithKline, Tesaro, Roche, Nucana, Chugai, and Verastem; Committee Member for the Scottish Medicines Consortium. CS: grant and research support from Clovis Oncology, Eisai Inc, Sierra Oncology, Roche, Beigene, AstraZeneca; membership on Advisory boards: AstraZeneca, Clovis Oncology, Roche, Eisai, Sierra Oncology, Takeda, MSD; committee membership on GCIG, IRCI (Chair), ANZGOG (Chair). DT: research funding from the National Medical Research Council (NMRC) Clinician Scientist Award Senior Investigator Grant (CSASI21jun-0003), the Pangestu Family Foundation Gynaecological Cancer Research Fund, and product samples from AstraZeneca, Eisai, and MSD (non-financial interest) for research trials; institutional research grants from AstraZeneca, Bayer, Karyopharm Therapeutics, and Roche; personal fees for advisory board membership from AstraZeneca, Bayer, BioNTech, Boehringer Ingelheim, Eisai, Genmab, GSK, MSD, PMV Pharma, Daiichi Sankyo and Roche; personal fees as an invited speaker from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, and Takeda; travel support from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, and Takeda; current non-renumerated role as protocol chair of Asia Pacific Gynecologic Oncology Trials Group (APGOT); previous non-renumerated role as Chair of the Asia Pacific Gynecologic Oncology Trials Group (APGOT); a previous non-renumerated role as the Society President of the Gynecologic Cancer Group Singapore; non-renumerated membership of the Board of Directors of the GCIG, and ownership of stocks/shares of Asian Microbiome Library (AMiLi). FA: participation on Advisory Board for MiMark. IM: consulting fees from AstraZeneca, Bicycle Therapeutics, Clovis Oncology/pharma, Duke Street Bio, Epsila Bio, Roche, Scancell, GSK, Theolytics, Transgene Biotek, and OncoC4; honoraria from GSK; participation on a Data Safety Monitoring Board or Advisory Board for Roche; unpaid trustee of Worldwide Cancer Research (charity). IRC: grants/contracts from AstraZeneca, Clovis, GSK, Mersana, BMS and MSD; honoraria from AstraZeneca, Clovis, GSK, Mersana, BMS and MSD, Roche, Pharmamar, Seagen, Eisai, Novartis; travel support from Roche, GSK, AstraZeneca, Pharmamar, MSD; participation on a Data Safety Monitoring Board or Advisory Board for Clovis, Deciphera, Adaptimmune, Sutro, Immunogen. JL: grants from AstraZeneca, Merck/MSD; consulting fees from AstraZeneca, Clovis Oncology, GSK, Artios Pharma, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Immagene, Incyte, Immunogen/Abbvie, Novocure; honoraria from AstraZeneca, MSD/Merck, Clovis Oncology, GSK; participation on a Data Safety Monitoring Board or Advisory Board for Mersana and SutroBio; Editor for ESMO Clinical Practice Guidelines – Gynaecological Cancer until December 2023; Past Vice President ESGO until 2021; Chair of National Ovarian Cancer Audit Committee. EMG-G: honoraria and travel support from AstraZeneca, Amgen, Merck and Eisai; participation on a Data Safety Monitoring Board or Advisory Board for Merck, AstraZeneca and Roche. HY: no relevant disclosures. KM: grants/contracts from PTC Therapeutics, Lilly, Clovis, Genentech, GSK, Verastem (all institutional); royalties or licenses from UptoDate; consulting fees from AstraZeneca, Aravive, Aadi, Blueprint pharma, Clovis, Caris, Duality, Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, Iovance, Janssen, Lilly, Mereo, Mersana, Merck, Myriad, Novartis, Novocure, Pannavance, Onconova, VBL Therapeutics, Verastem, Zentalis; honoraria from AstraZeneca, GSK, Immunogen, PRIME, RTP, Medscape, Great Debates and Updates; travel support from AstraZeneca, BioNTech, GOG P Associate Director. LH: support from Pfizer for meeting registration fees. LW: grants/contracts from Seagen, MSD, Roche, Gilead, German Cancer Aid and AstraZeneca (all institutional); consulting fees from Pfizer, MSD, Roche, Seagen, Eisai, GSK, Myriad and AstraZeneca; honoraria from Pfizer, MSD, Roche, Seagen, Eisai, GSK, Novartis and AstraZeneca; travel support from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for MSD, Roche, Seagen/Pfizer, Eisai, GSK and Myriad; leadership roles in German Vulva Cancer Group and current President of the European College for the Study of Vulval Disease. MF: consulting fees from AstraZeneca, Novartis, GSK, Incyclix; honoraria from AstraZeneca, GSK, MSD and The Limbic; participation on a Data Safety Monitoring Board or Advisory Board for AGITG IDSMB, ENDO-3; institutional research grants from AstraZeneca, Beigene and Novartis. NC: grants from AstraZeneca, PharmaMar and Roche; honoraria from AstraZeneca and Novartis; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris and Roche, Novocure; membership of the ESMO Guidelines Steering Committee; leadership role as Chair of the Alleanza Control il Tumore Ovarico (ACTO) Scientific Committee. OR: consulting fees from AstraZeneca, MSD, Medison, Neopharm; travel support from AstraZeneca and MSD; honoraria from AstraZeneca. PH: grants from AstraZeneca, Roche, GlaxoSmithKline, Genmab, Immunogen, Seagen, Clovis, Novartis; consulting fees from Miltenyi; honoraria from Amgen, AstraZeneca, GSK, Roche, Immunogen, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Mersana, Exscientia, Daiichi Sankyo, Karyopharm; travel support from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Roche, GlaxoSmithKline, Clovis, Immunogen, MSD, Miltenyi, Novartis, Eisai. SCC: meeting/travel support from AstraZeneca, MSD and GSK; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, MSD and GSK. SP: research funding from MSD, Roche, AstraZeneca, GSK, Pfizer and honoraria from MSD, AstraZeneca, GSK, Novartis, Pfizer, Pharmamar and Roche. YCL: institutional research grant from BeiGene; honoraria from AstraZeneca; participation on Advisory Board for AstraZeneca., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups. Specifically, there has been a systematic lack of data for underrepresented groups, with many studies failing to report or differentiate study participants based on sociodemographic domains, such as race and ethnicity. As such, the impact of treatment in these underrepresented groups is poorly understood, and clinical outcomes according to various sociodemographic factors are infrequently assessed. Inclusion of diverse trial participants, with different racial and ethnic background, is essential for the understanding of factors that may impact clinical outcomes. Therefore, we conducted a multi-national meeting of clinical trial groups and industry with the goal of increasing equity, diversity, and inclusion in gynecologic cancer clinical trials and to address barriers to recruitment, participation, and harmonization of data collection and reporting. These Gynecologic Cancer Intergroup (GCIG) statements present recommendations and strategies for the gynecologic cancer research community to improve equity, diversity, and inclusion in gynecologic cancer clinical trials., Competing Interests: Competing interests: Alison Brand reports grants/contracts from the Australian Government Department of Health and Aged Care Medical Research Future Fund, Australia and New Zealand Gynaecological Oncology Group (ANZGOG); and is Director ANZGOG, Chair GCIG. Michael Bookman reports consultancy fees paid to the institution from Immunogen independent DSMB. Sabrina Chiara Cecere reports travel support from AstraZeneca, Clovis, GSK, MSD; honoraria from AstraZeneca, Clovis, GSK, MSD; participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca, Clovis, GSK, MSD. Paul A. Cohen reports grants/contracts from the Australian Government Department of Health and Aged Care Medical Research Future Fund, Cancer Council Western Australia, Australia and New Zealand Gynaecological Oncology Group (ANZGOG); honoraria and educational events from AstraZeneca, MSD; advisory boards with AstraZeneca, Reliis; non-remunerated leadership roles as Director ANZGOG, Chair Research Advisory Committee ANZGOG, Education Committee Chair, International Gynecological Cancer Society, Expert Advisory Group Australian Centre for Prevention of Cervical Cancer, Editorial Board Member International Journal Gynecological Cancer; stock in Reliis Ltd. Jennifer Croke reports honoraria from American Society of Radiation Oncology (Member, Sexual and Gender Minority Affinity Working Group), Canadian Association of Radiation Oncology (Annual Scientific Meeting lead), Merck. Josie Ethier reports consultancy fees from AstraZeneca; honoraria from AstraZeneca, GSK, Merck; advisory board participation with AstraZeneca, Eisai, GSK, Merck. Franziska Geissler reports grants/contracts from International Research Fellowship, Swiss Cancer Research Foundation & Swiss Cancer League and Research Fund for Excellent Junior Researchers University of Basel 2024. Rosalind Glasspool reports grants/contracts from Clovis Oncology; consultancy fees from Clovis Oncology, GSK, Novartis; honoraria from GSK; travel support from GSK, MSD; participation on a Data Safety Monitoring Board or Advisory Board from IDMC Matao trial; leadership or fiduciary roles at IGCS Advocacy committee chair, IGCS board member, Chair of Scottish Gynaecological Cancer Trials Group; receipt of equipment, materials, drugs, medical writing, gifts or other services from AstraZeneca, GSK, Novartis; other financial or non-financial interests with Allarity Therapeutics, AstraZeneca, Immunogen, GSK. Philipp Harter reports grants/contracts from AstraZeneca, Clovis, Genmab, GSK, Immunogen, Novartis, Roche, Seagen; consultancy fees from Miltenyi; honoraria from Amgen, AstraZeneca, Clovis, Daiichi Sankyo, Eisai, Exscientia, GSK, Immunogen, Karyopharm, Mersana, MSD, Roche, Sotio, Stryker, Zai Lab; travel support from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board at AstraZeneca, Clovis, Eisai, GSK, Immunogen, MSD, Miltenyi, Novartis, Roche. Chee Khoon Lee reports grants/contracts from Amgen, AstraZeneca, Merck, Roche; honoraria from Amgen, AstraZeneca, Gilead, GSK, Janssen, Merck, Merck kGA, Novartis, Roche, Takeda. Kristina Lindemann reports grants/contracts from GSK (research funding paid to institution); honoraria, consultancy fees, or advisory board fees from AstraZeneca, Eisai, GSK, MSD, Nycode; part of the Data Safety Monitoring Committee for Karyopharm.Ainhoa Madariaga reports honoraria from AstraZeneca, Clovis, GSK, MSD, Pharma & PharmaMar; travel support from AstraZeneca, GSK, MSD; participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, AstraZeneca, GSK, MSD. Asima Mukhopadhyay reports grants/contracts from the Indian Council of Medical Research for the IPIRIC academic study which endorses the principles of EDIM; honoraria from KGOG; advisory board at CannariaBio; Secretary KolGoTrg, Executive Board Member GCIG; part funding support for the IPIROC trial for drug procurement from BDR Pharma. Amit Oza reports grants/contracts from Amgen, AstraZeneca; consultancy fees from BMS; advisory board participation with AstraZeneca and GSK; other financial or non-financial interests with AstraZeneca, GSK. Elisa Piovano reports travel support from AstraZeneca, GSK. Bhavana Pothuri reports grants/contracts from Agenus, Alkermes, AstraZeneca, Acrivon, Celgene, Celsion/Immunon, Clovis Oncology, Duality Bio, Eisai, Immunogen, Incyte, Imab, InxMed, Karyopharm Therapeutics, Lily, LOXO/Lily, Merck, Mersana, Novocure, Onconova, NRG Oncology, Roche/Genentech, Seagen, Sutro, Takeda, Tesaro/GSK, Toray, VBL Therapeutics, Xencor; consultancy fees from AstraZeneca, Celsion, Duality Bio, Eisai, GOG Foundation, Imvax Inc, Incyte Corporation, InxMed, Lily, Onconova Therapeutics, Regeneron, SeaGen, Signatera, Sutro Biopharma, Tesaro/GSK; honoraria from Albert Einstein-Montefiore, Bioascend, Colorado University, Curio, Lankenau Hospital, OncLive, PERS, PeerView, Vanium, Yale University; travel support from GOG Partners; advisory boards with AstraZeneca, Celsion/Immunon, GOG Foundation, Imab, Imvax, Incyte, InxMed, Lily, Merck, Mersana, Nuvation, Sutro, Tesaro/GSK; leadership or fiduciary roles in GOG Partners, NYOB Society VP, SGO Board of Directors, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce co-chair. Jose Alejandro Rauh-Hain reports grants/contracts from NIH, Department of Defense, American Cancer Society; support for the present manuscript from Guidepoint Consulting, Sago. Ora Rosengarten reports consultancy fees from AstraZeneca, Medison, MSD, Neopharm; travel support from AstraZeneca, MSD; lecture honoraria from AstraZeneca. Jalid Sehouli reports grants/contracts from AstraZeneca, Eisai, GSK, Merck, MSD, Novocure, Roche, Tesaro; consultancy fees from AstraZeneca, Clovis, Eisai, GSK, Immunogen, Incyte, MSD, Novocure; honoraria from AstraZeneca, Bristol Myers Squibb, Clovis, Eisai, GSK, Immunogen, Incyte, MSD, Novartis, Novocure; travel support from AstraZeneca, Eisai, GSK, Immunogen, Incyte, MSD, Novocure, Roche; advisory boards with AstraZeneca, Bayer, Bristol Myers Squibb, Clovis, GSK, Immunogen, Incyte, MSD, Novocure, PharmaMar; leadership or fiduciary roles at AGO, ASCO, Deutsche Stiftung Eierstockkrebs, ENGAGE, ESGO, GCIG, Medical writing (MSD). David Tan reports receiving research funding from the National Medical Research Council (NMRC) Clinician Scientist Award Senior Investigator Grant (CSASI21jun-0003), the Pangestu Family Foundation Gynaecological Cancer Research Fund; and product samples from AstraZeneca, Eisai, MSD (non-financial interest) for research trials. Institutional research grants from AstraZeneca, Bayer, Karyopharm Therapeutics, Roche; personal fees for advisory board membership from AstraZeneca, Bayer, BioNTech, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Genmab, GSK, MSD, PMV Pharma, Roche; personal fees as an invited speaker from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, Takeda; travel support from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, Takeda; current non-renumerated role as protocol chair of Asia Pacific Gynecologic Oncology Trials Group (APGOT); previous non-renumerated role as Chair of the Asia Pacific Gynecologic Oncology Trials Group (APGOT); a previous non-renumerated role as the Society President of the Gynecologic Cancer Group Singapore; non-renumerated membership of the Board of Directors of the GCIG; ownership of stocks/shares of Asian Microbiome Library (AMiLi). Toon Van Gorp reports consultancy fees (via institution) from AbbVie, AstraZeneca, BioNTech, Cancer Communications and Consultancy Ltd, Eisai, GSK, ImmunoGen, Incyte, Karyopharm, MSD/Merck, OncXerna Therapeutics, Seagen, Tubulis, Zentalis; corporate sponsored research (via institution) from Amgen, AstraZeneca, Roche; honoraria for lectures (via institution) from AstraZeneca, Eisai, GSK, ImmunoGen, MSD; travel support from AstraZeneca, ImmunoGen, MSD, PharmaMar; grants/contracts from Amgen, AstraZeneca, Roche; chair of the Belgian and Luxembourg Gynaecological Oncology Group. Stephen Welch reports honoraria from AstraZeneca, Eisai, GSK, Merck; advisory boards with Eisai, Incyte, GSK, Roche, Takeda.All other authors declare no conflict of interest., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts)., Patients and Methods: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts)., Results: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia., Conclusions: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified., (©2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy., Patients and Methods: ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1-positive populations (alpha .025 for each population)., Results: Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1-positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1-positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively)., Conclusion: ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1-positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.

Introduction: FDG PET/CT (fluorodeoxyglucose (FDG)-positron emission tomography (PET) computed tomography (CT)) imaging reflects functional-metabolic changes occurring within the malignant process in response to therapy. Since these changes usually precede anatomic alterations, this imaging technique is highly valuable in assessing response during and after therapy and is superior to CT. FDG PET/CT following initiation of cancer therapy has a prognostic value, predicting progression free survival and overall survival. In some malignancies FDG PET/CT can guide personalized medicine by tailoring therapy in accordance with the metabolic cancer response in the individual patient. In lymphoma patients, including Hodgkin's disease (HD) and diffuse large B-cell lymphoma (DLBCL), FDG PET/CT is useful for monitoring response and guiding therapy, both after and early during therapy. Various quantitative and visual criteria systems are used for assessing cancer response to therapy by FDG PET/CT. Acquaintance with these interpretation methods and their adjustment to new anti-cancerous mechanisms such as in immunotherapy, is important for accurate imaging and meaningful interpretation. Large prospective meticulously performed studies, using standardized methodology, are required to further establish and expand the use of FDG PET/CT for the assessment of response to therapy in various malignancies.

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0-10, 17.8%; RS 11-25, 62.5%; RS 26-100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0-10, 11-25, and 26-100: 2.6% (95% confidence interval [CI], 1.1-6.2%), 6.1% (95% CI, 4.4-8.6%), and 13.1% (95% CI, 9.4-18.3%), respectively ( P  < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1-5.1%), 2.2% (95% CI, 1.3-3.7%), and 9.5% (95% CI, 6.0-14.9%) ( P  < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0-10/11-25), 10-year distant recurrence and BCSM rates for RS 0-10 patients were 2.7% (95% CI, 1.1-6.5%) and 0.8% (95% CI, 0.1-5.3%), respectively, and for RS 11-25 patients, 5.7% (95% CI, 3.9-8.3%) and 2.0% (95% CI, 1.1-3.7%), respectively. For RS 11-25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0-25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26-100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches., Competing Interests: Competing interestsS.M.S. reports receiving grant funding from Teva; receiving travel expenses from Genomic Health, Inc.; conducting research funded by Teva. N.B. reports receiving honoraria from Teva, and serving on the speaker’s bureau of Genomic Health. D.M.J., J.B., and S.S. report being employed by Genomic Health. D.M.J., J.B., and S.S. report having stock ownership in Genomic Health. S.S. reports having intellectual property interest in Genomic Health and a leadership role at Genomic Health. L.S.G. reports being employed by and holding stock options in Teva Pharmaceutical Industries Ltd. A.B.S. reports being a consultant/medical writer for Teva Pharmaceutical Industries Ltd., Genomic Health Inc. (including for the purpose of the current study), Bayer, and Roche. M.S., S.R., B.U., G.F., O.R., A.I., B.N., D.K., M.L., M.T., N.L., and D.B.G. declare no competing interests., (© The Author(s) 2019.)

Vulvar metastasis is an unusual presentation of recurrent endometrial cancer and should be part of the differential diagnosis of vulvar lesion.

Background: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved., Method: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count., Results: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer)., Conclusion: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers., (© 2018 American Cancer Society.)

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 ( N  = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated ( n  = 27) and 2.9% in chemotherapy-untreated patients ( n  = 352); P  = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients ( n  = 102) was significantly lower than in untreated patients ( n  = 156) (1.0% vs. 9.7% P  = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated ( n  = 89) and 4.4% in chemotherapy-untreated patients ( n  = 488); P  = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score < 18.

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 ( n  = 304) and 11-25 ( n  = 1037) (TAILORx categorizatio n ) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P<0.001) in the dexrazoxane group, but no significant difference in the incidence of treatment delays or cancellations. The incidence of cardiac events was the same in both treatment groups with and without dexrazoxane. There was a nonsignificantly lower mortality rate in the dexrazoxane group (9.6%) compared with the nondexrazoxane group (15.0%) at data lock. Adding dexrazoxane to doxorubicin in adjuvant therapy patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions. No differences in events defined as cardiac toxicities were detected. Dexrazoxane had no detrimental effect on survival, despite the higher hematological toxicity, the older median age, and the higher prevalence of HER2-positive disease in the dexrazoxane group.

Objective: The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously., Methods: Eligible patients were treated with oral olaparib 400mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated., Results: In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received ≥3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26-42) and median DoR was 7.9 (95% CI 5.6-9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2months (95% CI 5.6-13.5) compared with 8.0months (4.8-14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib., Conclusion: Following ≥3 prior lines of chemotherapy, olaparib 400mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified., Competing Interests: Conflicts of interestSM Domchek has received research funding from AbbVie, AstraZeneca and Clovis Oncology; C Aghajanian has received honoraria from AstraZeneca, and has received travel allowance and acted in an advisory/consulting role for AbbVie; RK Schmutzler has acted in an advisory/consulting role, and has received honoraria and research funding from AstraZeneca; MW Audeh, M Friedlander, G Fried, SM Stemmer, A Hubert and B Kaufman have received research funding from AstraZeneca; J Balmaña has received honoraria and research funding, and acted in an advisory/consulting role for AstraZeneca; G Mitchell and O Rosengarten have acted in an advisory/consulting role for Astra Zeneca and have received research funding from AbbVie and AstraZeneca; JD Robertson and Helen Mann were employees and held stock in AstraZeneca at the time of the study.R Shapira-Frommer and N Loman declare no conflict of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers., Patients and Methods: This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate., Results: A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease ≥ 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade ≥ 3 AEs were reported for 54% of patients; anemia was the most common (17%)., Conclusion: Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies., (© 2014 by American Society of Clinical Oncology.)

Background: Docetaxel-based chemotherapy remains the treatment of choice in castration-resistant prostate cancer (CRPC). Generally, elderly patients poorly tolerate these drugs. Vinorelbine has a favolable toxicity profile and may be useful in elderly or unfit patients with castration-resistant prostate cancer., Purpose: The aim of this retrospective analysis was to evaluate the efficacy and safety of vinorelbine in patients with CRPC., Patients and Methods: We analyzed the medical records of patients with CRPC treated in our institution with intravenous vinorelbine as first line chemotherapy., Results: A total of 25 patients were assessable for efficacy. The median age was 73 years (range, 51-87 years); 9 out of 25 patients (36%) had a > 50% reduction in PSA levels from baseline. Mean progression-free survival was 7.2 months. Mean overall survival was 20.7 months. Mean overall survival for 11 patients treated with second-line taxane-based chemotherapy was 27.5 months compared to 16.8 months for patients who did not receive second-line chemotherapy. Treatment was generally well tolerated., Conclusion: On the basis of this small retrospective survey, we conclude that intravenous vinorelbine seems to be a therapeutic option in elderly or unfit patients with CRPC.

The aim of this study was to assess the clinical activity and toxicity of liposome-encapsulated doxorubicin citrate (Myocet) in a retrospective multicenter cohort of epithelial ovarian, primary peritoneal, and tubal cancer patients. Records of patients with recurrent epithelial ovarian, primary peritoneal, and tubal cancer treated with liposome-encapsulated doxorubicin citrate (60 mg/m on day 1 of a 21-day cycle) after failure of more than one previous regimen were reviewed. Fifty-three patients were evaluated for efficacy and toxicity. The median age of the patients was 59 (range 39-73). The median follow-up was 6 months (range 1-17). One patient (1.9%) showed a complete response and 13 patients (24.5%) showed a partial response, yielding an overall response rate of 26.4% (14/53 patients). Clinical benefit was achieved in 36 patients (67.9%). The median progression-free survival (PFS) for the entire study population was 4.0 months (range 1.0-14.8). The median PFS for platinum-sensitive and platinum-resistant patients was 4.0 months (ranges 1.0-14.8 and 1.0-9.4, respectively; P=0.652). The median overall survival from the start of liposome-encapsulated doxorubicin citrate was 10.0 months. Multivariate survival analysis showed no association between the liposome-encapsulated doxorubicin citrate line of treatment or platinum sensitivity to PFS in age and BRCA status-adjusted models. Only 11.3% of patients experienced grade 3-4 hematologic toxicities, 80% grade-2 alopecia, and 50% grade-1-2 fatigue. No other grade-4 toxicities, no significant cardiac events, or hand and foot syndromes were reported. Liposome-encapsulated doxorubicin citrate was well tolerated, with a good response and high clinical benefit rate. Further evaluation in a larger prospective cohort is warranted.

Aim: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma (ROC), following disease progression on single agent PLD., Methods: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years (range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve (AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were re-evaluated and responses to therapy based on computer tomography (CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS (V19)., Results: A median of 10 cycles (range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients., Conclusion: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.

Background and Objective: Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions., Patients and Methods: Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997-2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002-2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m2 for >3 months and were staged according to the National Kidney Foundation guidelines., Results: Thirteen patients (23%) developed stage ≥3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy., Conclusions: CKD is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.

Introduction: There are approximately 40,000 new cases of pancreatic adenocarcinoma diagnosed in the USA each year. It is estimated that 5-10% of all patients with pancreatic cancer have a first-degree relative with the disease, while up to 20% of cases have a hereditary component. Individuals who carry a germline mutation in the BRCA 1 or 2 genes have an increased lifetime risk of developing pancreatic adenocarcinoma when compared with the general population., Case Report: Here, we present a case of metastatic pancreatic adenocarcinoma arising in a 67-year-old carrier of a BRCA 1 germline mutation., Discussion: In patients with known BRCA 1 or 2 mutation-associated pancreatic adenocarcinoma, the addition of a DNA cross-linking agent such as cisplatin, oxaliplatin, or mitomycin to a standard gemcitabine chemotherapy backbone should be considered. Poly ADP-ribose inhibitors are a novel class of drug, which have demonstrated promising efficacy in trials of BRCA 1 and 2 mutant breast and ovarian cancer, and are currently undergoing prospective evaluation in advanced pancreatic cancer.

Background: Primary malignant melanoma of the vagina is extremely rare, accounting for 0.3-0.8% of all malignant melanomas. True amelanotic vaginal melanoma showing no melanin on histological examination is exceedingly rare, accounting for only 2% of all vaginal melanomas., Case Report: We describe a 31-year-old female patient who presented with locally advanced amelanotic melanoma of the vagina, with no evidence of metastatic spread on the computerized tomography (CT) scan, but who was subsequently diagnosed as suffering from metastatic disease by positron emission tomography (PET)-CT performed a few weeks following posterior pelvic exenteration., Conclusion: Specific immunohistochemical staining with melanoma markers should be performed to confirm or exclude a diagnosis of amelanotic melanoma in all patients presenting with a vaginal mass composed of undifferentiated epithelioid malignant cells. Fluorodeoxyglucose (FDG)-PET-CT should be performed as part of the preoperative evaluation, to identify the presence or absence of metastatic disease in all patients with vaginal melanoma., (Copyright 2008 S. Karger AG, Basel.)