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Purpose: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an extremely rare, highly aggressive cancer (mean age of onset, 24 years). Nearly all cases are associated with somatic or germline pathogenic variants (GPVs) in SMARCA4. Early bilateral oophorectomy is recommended for unaffected females with a SMARCA4 GPV. However, the penetrance of SMARCA4 GPVs for SCCOHT is highly uncertain and subject to ascertainment bias., Methods: Leveraging the early-onset, sex-specific, highly morbid nature of SCCOHT, we hypothesized that the penetrance for SCCOHT could be quantified from the deficit in SMARCA4 GPVs in females compared with males in UK Biobank, a population cohort for which recruitment was restricted to those age 40 to 69. We also analyzed pedigrees ascertained internationally by the Montreal-based SCCOHT-SMARCA4 Registry., Results: We observed SMARCA4 GPVs in 8/210,182 (0.0038%) female and 18/179,210 (0.0100%) male participants in UK Biobank (P = .028), representing a male:female odds ratio of 2.64 (95% CI 1.09-7.02), implying a penetrance of 62% for SCCOHT (given the absence of other SMARCA4-related female-specific early morbid diseases). A deficit of GPVs in females in UK Biobank was also demonstrated for BRCA1 and TP53., Conclusion: Our findings support bilateral oophorectomy in early adulthood as a rational choice for at-risk females with SMARCA4 GPVs., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Novel biomarkers are needed to direct new treatments for ovarian cancer, a disease for which the standard of care remains heavily focused on platinum-based chemotherapy. Despite the success of PARP inhibitors, treatment options are limited, particularly in the platinum-resistant setting. NaPi2b is a cell surface sodium-dependent phosphate transporter that regulates phosphate homeostasis under normal physiological conditions and is a lineage marker that is expressed in select cancers, including ovarian, lung, thyroid, and breast cancers, with limited expression in normal tissues. Based on its increased expression in ovarian tumors, NaPi2b is a promising candidate to be studied as a biomarker for treatment and patient selection in ovarian cancer. In preclinical studies, the use of antibodies against NaPi2b showed that this protein can be exploited for tumor mapping and therapeutic targeting. Emerging data from phase 1 and 2 clinical trials in ovarian cancer have suggested that NaPi2b can be successfully detected in patient biopsy samples using immunohistochemistry, and the NaPi2b-targeting antibody-drug conjugate under evaluation appeared to elicit therapeutic responses. The aim of this review is to examine literature supporting NaPi2b as a novel biomarker for potential treatment and patient selection in ovarian cancer and to discuss the critical next steps and future analyses necessary to drive the study of this biomarker and therapeutic targeting forward., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [S. Banerjee: research funding: AstraZeneca, GlaxoSmithKline, Verastem; advisory boards: Amgen, AstraZeneca, GlaxoSmithKline, Immunogen, Merck & Co., Mersana, Novartis, OncXerna, Regeneron, Seagen, Shattuck; honoraria: Amgen, AstraZeneca, Clovis, GlaxoSmithKline, Immunogen, Merck & Co., Mersana, Pfizer, Roche, Takeda; stock or other ownership: Perci Health. R. Drapkin: advisory boards: Repare Therapeutics and VOC Health, Inc. D. Richardson: Consultancy/advisory role with Mersana, AstraZeneca, Genentech, GlaxoSmithKline, Immunogen, and Deciphera; research funding from GlaxoSmithKline, Celsion, Roche, Aravive, Shattuck, Mersana, Syros, Arch Oncology, Harpoon, Hookipa, Clovis, and Karyopharm. M. Birrer: advisory boards: AstraZeneca, Merck.]., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma., Methods: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m 2 by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40-50 mg/m 2 by body surface area once every 4 weeks; intravenous topotecan 4 mg/m 2 by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting., Findings: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9-15·0) compared with 7·2 months (5·6-9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36-0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths., Interpretation: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma., Funding: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis., Competing Interests: Declaration of interests DMG reports payments made to his institution from the National Cancer Institute (NRG Oncology), Novartis, and the GOG Foundation for this study; royalties or licenses from Elsevier and UpToDate outside the submitted work; consulting fees from Genentech outside the submitted work; personal fees for service as a member of the Committee of the National Cancer Institute outside the submitted work; and stock or stock options from Johnson & Johnson, Bristol Myers Squibb, and Biogen outside the submitted work. AM reports service as a masked study statistician for VBL Therapeutics; provision of statistical institutional support for Advaxis; service as a data safety monitoring board reporting statistician for Regeneron; and service on a study steering committee for Genentech and AstraZeneca, all outside the submitted work. RLC reports consulting fees from AstraZeneca, Merck–GlaxoSmithKline, and Clovis; grants from Genmab, Genentech–Roche, Janssen, Agenus, Regeneron, and OncoQuest; payments or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from AstraZeneca, Merck–GlaxoSmithKline, and Clovis; and service on a data safety monitoring board or an advisory board for Janssen, VBL Therapeutics, and AstraZeneca, all outside the submitted work. KNM reports service on advisory boards for Alkemeres, AstraZeneca, Aravive, Blueprint Medicines, Eisai, Elevar, GlaxoSmithKline–Tesaro, Genentech–Roche, Hengrui, Immunogen, IMab, Merck, Mereo, Mersana, Myriad, OncXerna, Onconova, Novartis, Sorrento, Tarveda, and VBL Therapeutics, all outside the submitted work; grant funding from PTC Therapeutics, Lilly, Merck, and Genentech–Roche outside the submitted work; funding paid to her institution from Cyteir, Immunocore, Bolt Bio, Amgen, Artios, GlaxoSmithKline–Tesaro, Mereo, Regeneron, Aravive, Verastem, and AstraZeneca, for all of which she also serves as a local principal investigator; serving as national principal investigator for the IMaGYN050 trial of ovarian cancer (Genentech–Roche), the MIRASOL trial of ovarian cancer (Immunogen), the Relevare study of ovarian cancer (OncXerna), the FIRST study of ovarian cancer (GlaxoSmithKline–Tesaro), and the ETCTN 10422 study of ovarian cancer (National Cancer Institute); being the associate director for GOG Partners, on the GOG Foundation board of directors, and the NRG Oncology chair of the ovarian cancer committee; and receiving speaking reimbursement from PER, Research to Practice, Medscape, Great Debates and Updates, and Gyn Mal, all of which are outside the scope of this work but were active during the conduct of this study. SB reports grants paid to their institution from AstraZeneca, Tesaro, and GlaxoSmithKline; personal fees for participation in advisory boards from Amgen, AstraZeneca, Genmab, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Merck Serono, Mersana, Oncxerna, Seagen, Shattuck Lab, and Epsilogen; and personal fees for lectures from Amgen, AstraZeneca, Clovis, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Mersana, Pfizer, Roche, and Takeda, all outside the submitted work. AAS reports a National Cancer Trial Network grant; grants paid to her institution from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Clovis, Eisai, Immutep, Merck, OncoQuest, PharmaMar, Genentech–Roche, Seagen, Tesaro–GlaxoSmithKline, and VBL Therapeutics; consulting fees from Aravive, AstraZeneca, Clovis, Cordgenics, Eisai, Merck, Mersana, Myriad, Oncoquest, Genentech–Roche, and Tesaro–GlaxoSmithKline; presentations for educational events on cervical cancer sponsored by Research to Practice; service on advisory boards (uncompensated) for AbbVie and Regeneron; service on clinical trial steering committees (all uncompensated) for the AtTEnd trial (Hoffman-LaRoche), the Oval Trial (VBL Therapeutics), and the FLORA-5 trial (Oncoquest); and service on the GOG Foundation Board of Directors, the Society of Gynecologic Oncology Board of Directors, and the American Association of Obstetricians and Gynecologists Foundation Board of Trustees, all outside the submitted work. DMO reports National Cancer Institute support for this clinical trial; research funding paid to their institution from AstraZeneca, Tesaro–GlaxoSmithKline, Immunogen, Janssen–Johnson & Johnson, AbbVie Regeneron, Amgen, Novocure, Genentech–Roche, VentiRx Array Biopharma EMD Serono, Ergomed, Ajinomoto, Ludwig Cancer Research Stemcentrx, Cerulean Pharma, the GOG Foundation, the National Cancer Institute, Bristol Myers Squibb, C Serono, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, inVentiv Health Clinical, Iovance Biotherapeutics, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, and Clovis; personal fees for consulting or advisory board membership, or both, from AstraZeneca, Tesaro–GlaxoSmithKline, Immunogen, Ambry, Janssen–Johnson & Johnson, BBI, Agenus, AbbVie, Regeneron, Amgen, Novocure, Genentech–Roche, GOG Foundation, Iovance Biotherapeutics, Myriad Genetics, Eisai, Agenus, Tarveda, Merck, SeaGen, Novartis, Mersana, Clovis, Rubius, and Elevar, all outside the submitted work. OD reports grants or contracts from AstraZeneca, Clovis, Genentech, AbbVie, IMV, Millenium, and Pharmamar; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Tesaro–GlaxoSmithKline and AstraZeneca; payment for expert testimony in one legal case unrelated to the current study; and participation on a data safety monitoring board or advisory board for Merck, Clovis, PACT, and Genentech, all outside the submitted work. SG reports financial support paid to her institution for the present study from the National Clinical Trials Network; grants or contracts from AstraZeneca, AbbVie, Pfizer, Rigel, Iovance, Tesaro, Genentech–Roche, PharmaMar, and GlaxoSmithKline; patents licensed to Sermonix (US patent numbers 10,905,659 and 10,258,604); participation on a data safety monitoring board or advisory board for Sermonix, Elevar Therapeutics, and GlaxoSmithKline; and service as an NRG Oncology phase 1 subcommittee co-chair, all outside the submitted work. BS reports personal fees for service on advisory boards for Abbvie, AstraZeneca, Bostongene, Clovis, Eisai, Genentech, GlaxoSmithKline, Jazz Pharmaceticals, Lilly, Merck, Myriad, Novartis, Nuvation, Onconova, and Seagen; and consulting for the GOG Foundation, all outside the submitted work. AE reports grants or contracts from UKRI for a post-doctoral fellowship outside the submitted work. CG reports grants from GlaxoSmithKline and Novartis for this study (trametinib, the test drug, was sold by GlaxoSmithKline to Novartis during the course of the study). WEB, JP, KCa, WR, DM, KCo, HG, PH, JF, MC, RLH, CSH, HQH, and LW declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Poly-(ADP)-ribose polymerase inhibitors (PARPi) are a class of oral anticancer drugs first developed as "synthetically lethal" in cancers harboring BRCA1/BRCA2 inactivating mutations. In high-grade serous or endometrioid ovarian cancers (HGOC), PARPi demonstrated benefit as maintenance therapy in relapsing BRCA-mutated and non-mutated tumors. Recently, they extended their indications to frontline maintenance therapy. This review summarizes the current place of PARPi (i) as maintenance or single agent in recurrent disease and (ii) frontline maintenance with different settings. We reviewed the course of biomarker identification, the challenge of overcoming resistance to PARPi and future combinations with targeted therapies, including anti-angiogenic, immune checkpoint inhibitors and DNA damage response inhibitors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ovarian cancer is a deadly malignancy with a growing therapeutic armamentarium, though achieving sustained benefit in the clinic remains largely elusive. Through biomarker and genetic analysis, several pathways of resistance and sensitivity to commonly used therapeutics have been identified, expanding the potential of identifying unique drug combinations and indicating new directions for improving clinical outcomes. Here, we review the mechanisms of angiogenic response and antiangiogenic therapy in ovarian cancer, as well as the interactions it exhibits with the immune and DNA damage response pathways. We discuss results from clinical trials examining the combinations of antiangiogenics, PARP inhibitors, and immune checkpoint inhibitors are also discussed, as well as several ongoing trials., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To report clinician-perceived changes to cancer service delivery in response to COVID-19., Design: Multidisciplinary Australasian cancer clinician survey in collaboration with the European Society of Medical Oncology., Setting: Between May and June 2020 clinicians from 70 countries were surveyed; majority from Europe (n=196; 39%) with 1846 COVID-19 cases per million people, Australia (AUS)/New Zealand (NZ) (n=188; 38%) with 267/236 per million and Asia (n=75; 15%) with 121 per million at time of survey distribution., Participants: Medical oncologists (n=372; 74%), radiation oncologists (n=91; 18%) and surgical oncologists (n=38; 8%)., Results: Eighty-nine per cent of clinicians reported altering clinical practices; more commonly among those with versus without patients diagnosed with COVID-19 (n=142; 93% vs n=225; 86%, p=0.03) but regardless of community transmission levels (p=0.26). More European clinicians (n=111; 66.1%) had treated patients diagnosed with COVID-19 compared with Asia (n=20; 27.8%) and AUS/NZ (n=8; 4.8%), p<0.001. Many clinicians (n=307; 71.4%) reported concerns that reduced access to standard treatments during the pandemic would negatively impact patient survival. The reported proportion of consultations using telehealth increased by 7.7-fold, with 25.1% (n=108) of clinicians concerned that patient survival would be worse due to this increase. Clinicians reviewed a median of 10 fewer outpatients/week (including non-face to face) compared with prior to the pandemic, translating to 5010 fewer specialist oncology visits per week among the surveyed group. Mental health was negatively impacted for 52.6% (n=190) of clinicians., Conclusion: Clinicians reported widespread changes to oncology services, in regions of both high and low COVID-19 case numbers. Clinician concerns of potential negative impacts on patient outcomes warrant objective assessment, with system and policy implications for healthcare delivery at large., Competing Interests: Competing interests: Some authors of this manuscript hold leadership positions on the ESMO board., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the latest breakthrough in the management of newly diagnosed advanced ovarian cancer. The results of the SOLO-1 trial in 2018 led to European Medicines Agency and Food and Drug Administration approval of olaparib as first-line maintenance therapy in patients with BRCA1/2 mutation, establishing a new standard of care. Subsequently, the results of three phase III trials (PRIMA, PAOLA-1, VELIA) evaluating the use of first-line PARP inhibitors beyond patients with BRCA1/2 mutations and as combination strategies were presented in 2019, leading to the recent approval of maintenance niraparib irrespective of biomarker status and olaparib in combination with bevacizumab in homologous recombination deficiency-positive-associated advanced ovarian cancer. An ESMO Open - Cancer Horizons round-table expert panel discussed the four phase III trials of first-line PARP inhibitor therapy and how they are changing the clinical management of advanced ovarian cancer., Competing Interests: Competing interests: SB: Institution research grants: Astrazeneca, Tesaro, GSK. Received honoraria for advisory boards Astrazeneca, Amgen, Clovis Oncology, Genmab, GSK, Immunogen, Merck Sereno, MSD, Mersana, Pfizer, Roche, Seattle Genetics, Tesaro. Support for travel or accommodation: Nucana, Tesaro. AGM: has served on advisory boards for Clovis Oncology, Amgen, AstraZeneca, Genmab/Seattle Genetics, Immunogen, MSD, Mersana, PharmaMar, Roche, and Tesaro/GSK, AMGEN, Merck, Novartis, Oncoinvent, received support for travel or accommodation from AstraZeneca, Pharmamar, GSK and Roche and institutional research funding from Roche and GSK/Tesaro. Lead Investigator PRIMA. PH: has served on advisory boards for Astra Zeneca, Roche, Tesaro, GSK, Lilly, Clovis, Immunogen, MSD/Merck, received honoraria (e.g. for lectures) from Astra Zeneca, Roche, Sotio, Tesaro, Stryker, ASCO, Zai Lab, MSD and institutional research funding from Astra Zeneca, Roche, Tesaro, Genmab, DFG, European Union, DKH, Genmab. DL: has served on advisory boards for Clovis Oncology, AstraZeneca, Genmab/Seattle Genetics, MSD, ImmunoGen, PharmaMar, Roche, MSD, Merck Serono, Amgen and Tesaro/GSK, received support for travel or accommodation from AstraZeneca, GSK and Roche and institutional research funding from Merck, GSK, Clovis, Pharmamar KM: has served on advisory boards for Aravive, Astra Zeneca, Abbvie, Eisai, Genentech/Roche, GSK/Tesaro, Immunogen, Merck, Myriad, Mersana, Tarveda, VBL Therapeutics. Lead Investigator SOLO-1. AO: has served on advisory boards for Clovis Oncology, AstraZeneca, Genmab/Seattle Genetics, MSD, Mersana, PharmaMar, Roche, Deciphera, Merck and Tesaro/GSK, received support for travel or accommodation from AstraZeneca, PharmaMar, Tesaro and Roche. IRC: has served on advisory boards for Clovis Oncology, AstraZeneca, Genmab/Seattle Genetics, MSD, Mersana, PharmaMar, Roche, and Tesaro/GSK, received support for travel or accommodation from AstraZeneca, GSK and Roche and institutional research funding from MSD, GSK. Lead Investigator PAOLA-1., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Introduction: Over one million people in the UK identify as LGBTQ+ (lesbian, gay, bisexual, transgender, queer or questioning). Research has shown that this population experience differing cancer risk factors compared with non-LGBTQ+ patients and persistent inequalities in cancer care. Literature concerning the knowledge of oncologists of this group's healthcare needs is limited; our study aimed to evaluate knowledge, attitudes and behaviours of UK oncologists about LGBTQ+ patients., Methods: A 53-question survey was delivered via a secure online platform. Questions covered respondent demographics, knowledge, attitudes and behaviours with the majority of responses on a Likert scale. Oncologists were recruited via email from professional bodies and social media promotion. Informed consent was sought and responses fully anonymised. Multifactorial ordinal logistic regression and Fisher's exact test were used to assess for interactions between demographics and responses with Holm-Bonferroni multiple testing correction., Results: 258 fully completed responses were received. Respondents had a median age of 43 years (range 28-69); 65% consultants and 35% registrars; 42% medical, and 54% clinical, oncologists. 84% felt comfortable treating LGBTQ+ patients but only 8% agreed that they were confident in their knowledge of specific LGBTQ+ patient healthcare needs. There were low rates of routine enquiry about sexual orientation (5%), gender identity (3%) and preferred pronouns (2%). 68% of oncologists felt LGBTQ+ healthcare needs should be a mandatory component of postgraduate training., Conclusions: This survey showed that UK oncologists feel comfortable treating LGBTQ+ patients but may fail to identify these patients in their clinic, making it more difficult to meet LGBTQ+ healthcare needs. There is self-awareness of deficits in knowledge of LGBTQ+ healthcare and a willingness to address this through postgraduate training. Educational resources collated and developed in accordance with this study would potentially improve the confidence of oncologists in treating LGBTQ+ patients and the cancer care these patients receive., Competing Interests: Competing interests: AMB reports personal fees from Pfizer Oncology, outside the submitted work. SB reports grants and personal fees from Astrazeneca/MSD, grants and personal fees from GSK/Tesaro, personal fees from Clovis, personal fees from Immunogen, personal fees from Mersana, personal fees from Roche, personal fees from Amgen, personal fees from Seattle Genetics, personal fees from Genmab and personal fees from Merck Sereno, outside the submitted work., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer., Methods: In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC-IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m 2 paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m 2 paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m 2 paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3)., Findings: Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m 2 in group 1; 1233 mg/m 2 in group 2; 1274 mg/m 2 in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0-26·0] in group 1, 24·9 months [24·0-25·9] in group 2, 25·3 months [23·9-26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6-not reached] in group 1, 20·8 months [11·9-59·0] in group 2, 21·0 months [12·0-54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups., Interpretation: Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations., Funding: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Breast and ovarian cancer are common malignancies among older adults, causing significant morbidity and mortality. Although most cases of breast and ovarian cancer are sporadic, a significant proportion is caused by mutations in cancer susceptibility genes, most often breast cancer susceptibility genes (BRCA) 1 and 2. Furthermore, some breast and ovarian tumors are phenotypically similar to those with BRCA mutations, a phenomenon known as "BRCAness". BRCA mutations and "BRCAness" lead to defects in DNA repair, which may be a target for therapeutic agents such as Poly ADP-Ribose Polymerase (PARP) inhibitors. PARP inhibitors are novel medications which lead to double-strand breaks resulting in cell death due to synthetic lethality, and which have been shown to be effective in patients with advanced breast and ovarian cancers with or without BRCA mutations. Three different PARP inhibitors (olaparib, niraparib, and rucaparib) have been approved for the treatment of ovarian cancer and one (olaparib) for breast cancer harboring BRCA mutations. Here, we review the currently available evidence regarding the use of PARP inhibitors for the treatment of patients with breast and ovarian cancer, with a particular focus on the inclusion of older adults in clinical trials of these therapies. Additionally, we provide an overview of currently ongoing studies of PARP inhibitors in breast and ovarian cancer, and include recommendations for increasing the evidence-base for using these medications among older patients., (Copyright © 2018. Published by Elsevier Ltd.)

Background: While the global workforce is approaching gender parity, women occupy a small number of management level positions across most professions, including healthcare. Although the inclusion of women into the membership of many oncology societies has increased, the under-representation of women in leadership roles within international and national oncology societies remains relatively consistent. Moreover, the exact status of women participating as board members or presidents of oncology societies or as speakers at oncology congresses was undocumented to date., Methods: The database used in this analysis was derived from data collection performed by the European Society for Medical Oncology for the years 2015-2016 and data analyses performed using the Statistical Analysis Software V.9.3 and R language for statistical computing V.3.4.0 by Frontier Science Foundation-Hellas. The literature search was performed by the authors., Results: We report the presence of a gender gap within oncology. Results regarding the under-representation of women occupying leadership roles in oncology show female participation as members of the board or presidents of national and international oncology societies and as invited speakers at oncology congresses remains below 50% in the majority of societies included in this analysis. Women in leadership positions of societies was associated with a higher percentage of female invited speakers at these societies' congresses (p=0.006)., Conclusion: The full contribution that can be attained from using the potential of women in leadership roles is currently under-realised. Examples of how gender and minority participation in organisations improves outcomes and creativity are provided from science, clinical practice and industry that show outcomes are greatly improved by collective participation of both men and women. Although there are programmes in place in many oncology organisations to improve this disparity, the gender gap is still there. Ongoing discussion may help to create more awareness in the effort to accelerate the advancement of women within oncology., Competing Interests: Competing interests: EH-T is an employee of Janssen, the Pharmaceutical Company of Johnson & Johnson Europe, and a shareholder of Johnson & Johnson. DA has received research funding and/or honoraria from Roche, Merck Serono, Bayer Healthcare, Servier, BTG, Terumo, Sanofi Oncology, Eli Lilly and has participated in non-financial roles as ECCO Executive Board member, ECCO Oncopolicy Group member, EORTC Task Force member (Gastrointestinal cancers)—Global PI function with MOLOGEN, IMPALA trial (MGN 1703 as investigative agent). GC has received research funding and/or honoraria from Roche, Novartis, Pfizer and has participated in non-financial roles as a member of Steering Committee in clinical trials, member of data safety monitoring committee for clinical trials. EG has participated as Advisor for Roche, Neomed Therapeutics and Ellypses Pharma. MCG has received research funding and/or honoraria from MSD, BMS, Roche Astra Zeneca, Takeda and Eli Lilly. CR has been a consultant for BMS, Roche, Novartis, Pierre Fabre, MDS and Amgen. CS is a Scientific Consultant for SAKK (Swiss group for cancer research treatment) and has participated in non-financial roles as the ESGO Vice President, Principal Investigator for the Icon 8B Study, EUPATI Switzerland. SP has received research funding and/or honoraria from Genentech/Roche, Pfizer, Eli Lilly, MSD, Merck Serono, BMS, Novartis, Astra Zeneca, Boehringer Ingelheim, Amgen, Clovis, Regeneron, Janssen, Takeda and has participated in non-financial roles on the IASLC Board of Directors 2014–2017, SAKK lung group Vice-president, SAMO Vice-president, Froome Past President (2011–2017), ETOP Foundation Council/Scientific coordinator, ESMO president elect 2010–2021, PI ALEX trial, Genentech Steering committee, PI academic trials ETOP, EORTC/SAKK, FMH, IASLC, AACR.

Background: Although women account for a growing proportion of the oncology workforce, there is evidence they are under-represented in leadership roles. To gain further insights into this issue and extend understanding of gender challenges, the European Society for Medical Oncology Women for Oncology (W4O) Committee undertook a survey of female and male oncologists in 2016., Design: The 2016 W4O questionnaire included questions on (1) Demographics and professional environment, (2) Gender impact on career development, (3) Challenges for career progression and inappropriate behaviour experienced in the workplace, (4) Barriers for gender parity and (5) The gender gap. Between July and September 2016, the online survey was available to male and female clinical and academic oncology healthcare professionals in the EU and internationally., Results: Responses were analysed from 462 oncologists, of whom 76.7 % were women. Of female respondents, 45.5 % had a managerial or leadership role, compared with 65 % of male respondents (p<0.001). Men were more likely to have leadership roles, even in clinical teams with more women than men. Women respondents were more likely to consider their gender had a major impact on their career than men: 35.9 % vs 20.9 % (p<0.001). The biggest challenge to career progression for women was work and family balance (64.2%). Of female respondents, 14.4 % believed there had been significant or major progress in closing the gender pay gap compared with 39.3 % of men (p<0.001). Of female participants, 37.7 % reported they had encountered unwanted sexual comments by a superior or colleague., Conclusions: New initiatives are needed to address under-representation of women oncologists in leadership roles, including greater and concrete promotion of work-life balance, development and leadership training for women, and more support for flexible working. The fact that over a third of women in the survey had encountered unwanted sexual comments at work is of great concern and must be urgently addressed., Competing Interests: Competing interests: DA has received research funding and/or honoraria from Roche, Merck Serono, Bayer Healthcare, Servier, BTG, Terumo, Sanofi Oncology, Eli Lilly and has participated in non-financial roles as ECCO Executive Board member, ECCO Oncopolicy Group member, EORTC Task Force member (Gastrointestinal cancers)—Global PI function with MOLOGEN, IMPALA trial (MGN 1703 as investigative agent). GC has received research funding and/or honoraria from Roche, Novartis, Pfizer and has participated in non-financial roles as a member of Steering Committee in clinical trials, member of data safety monitoring committee for clinical trials. MCG has received research funding and/or honoraria from MSD, BMS, Roche Astra Zeneca, Takeda and Eli Lilly. EG has participated as Advisor for Roche, Neomed Therapeutics and Ellypses Pharma. EH-T is an employee of Janssen, the Pharmaceutical Company of Johnson & Johnson Europe, and a shareholder of Johnson & Johnson. CR has been a consultant for BMS, Riche, Novartis, Pierre Fabre, MDS and Amgen. CS is a Scientific Consultant for SAKK (Swiss group for cancer research treatment) and has participated in non-financial roles as the ESGO Vice President, Principal Investigator for the Icon 8B Study, EUPATI Switzerland. SP has received research funding and/or honoraria from Genentech/Roche, Pfizer, Eli Lilly, MSD, Merck Serono, BMS, Novartis, Astra Zeneca, Boehringer Ingelheim, Amgen, Clovis, Regeneron, Janssen, Takeda and has participated in non-financial roles on the IASLC Board of Directors 2014–2017, SAKK lung group Vice-president, SAMO Vice-president, Froome Past President (2011–2017), ETOP Foundation Council/Scientific coordinator, ESMO president elect 2010–2021, PI ALEX trial, Genentech Steering committee, PI academic trials ETOP, EORTC/SAKK, FMH, IASLC, AACR.

The cancer burden is rising globally with an increasing need for oncologists. The significant demands associated with caring for cancer patients within a rapidly evolving scientific field, poses manifold challenges, including the risk of work-related burnout. Surveys have already shown that the prevalence of burnout in oncologists worldwide is significant. There is growing concern that burnout has a detrimental impact on the wellbeing of oncologists and their patients. In this review article, we provide an oncologist's perspective on this important and topical issue. We have summarised the literature with regard to the consequences of physician burnout, its associated risk factors and previously evaluated solutions. We conclude by suggesting further strategies for addressing this problem., (Copyright © 2018. Published by Elsevier Ltd.)

The cancer burden is rising globally, exerting significant strain on populations and health systems at all income levels. In May 2017, world governments made a commitment to further invest in cancer control as a public health priority, passing the World Health Assembly Resolution 70.12 on cancer prevention and control within an integrated approach. In this manuscript, the 2016 European Society for Medical Oncology Leadership Generation Programme participants propose a strategic framework that is in line with the 2017 WHO Cancer Resolution and consistent with the principle of universal health coverage, which ensures access to optimal cancer care for all people because health is a basic human right. The time for action is now to reduce barriers and provide the highest possible quality cancer care to everyone regardless of circumstance, precondition or geographic location. The national actions and the policy recommendations in this paper set forth the vision of its authors for the future of global cancer control at the national level, where the WHO Cancer Resolution must be implemented if we are to reduce the cancer burden, avoid unnecessary suffering and save as many lives as possible., Competing Interests: Competing interests: AE: Currently conducting research sponsored by AstraZeneca, Pfizer, Celltrion, Novartis, Roche. JT: Advisory Boards for Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Genentech, Lilly, MSD, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Symphogen, Taiho, and Takeda. FCi: Advisory Boards: Merck Serono, Amgen, Roche, Bayer, Lilly, Servier. Research funding: Bayer, Roche, Merck Serono. GP: Honorarium for advisory boards or speakers fee: Roche, Celgene, Shire, Merck, Amgen, Lilly, BMS, Servier, Taiho, Halozyme, Sanofi. PC: Honoraria for consultancy/advisory role and/or for lectures from: Bayer, Blueprint Medicines, Deciphera Pharmaceuticals, Eisai, Eli Lilly, Nektar Ther., Novartis, Pfizer, PharmaMar. At his institution, his Unit received funds for research from: AmgenDompé, Arog Pharmaceuticals, Bayer, Eisai, Eli Lilly, Daiichi Sankyo Pharma, Epizyme Inc., Novartis, PharmaMar. MS: Conducts research sponsored by Janssen Pharmaceuticals. Advisory Boards: BMS, Novartis, Janssen Pharmaceuticals, Leo Pharma. Speaker bureau for BMA, Novartis. Travel funding: Novartis, BMS, Astellas, Ipsen. All other authors declare no competing interests related to this paper.

Peritoneal mesothelioma (MPeM) is a scarce abdominal-pelvic malignancy that presents with non-specific features and exhibits a wide clinical spectrum from indolent to aggressive disease. Due to it being a rare entity, there is a lack of understanding of its molecular drivers. Most treatment data are from limited small studies or extrapolated from pleural mesothelioma. Standard treatment includes curative surgery or pemetrexed-platinum palliative chemotherapy. To date, the use of novel targeted agents has been disappointing. Described is the management of two young women with papillary peritoneal mesothelioma with widespread recurrence having received platinum-pemetrexed chemotherapy. Both patients obtained symptomatic and disease benefit with apitolisib, a dual phosphoinositide 3-kinase-mammalian target of rapamycin (PI3K-mTOR) inhibitor for subsequent relapses, with one patient having a partial response for almost 3 years. Both are alive and well 10-13 years from diagnosis., Conclusion: These case presentations highlight a subgroup of rare MPeM that behave indolently that is compatible with long-term survival. This series identifies the use of targeted therapies with PI3K-mTOR-based inhibitors as a novel approach, warranting further clinical assessment. Development of prognostic biomarkers is essential to aid identify tumour aggressiveness, help stratify patients and facilitate treatment decisions., Competing Interests: Competing interests: None declared.

The European Society for Medical Oncology (ESMO) is one of the leading societies of oncology professionals in the world. Approximately 30% of the 13 000 ESMO members are below the age of 40 and thus meet the society's definition of young oncologists (YOs). ESMO has identified the training and development of YOs as a priority and has therefore established a comprehensive career development programme. This includes a leadership development programme to help identify and develop the future leaders in oncology. Well-trained and highly motivated future generations of multidisciplinary oncologists are essential to ensure the optimal evolution of the field of oncology with the ultimate goal of providing the best possible care to patients with cancer. ESMO's career development portfolio is managed and continuously optimised by several dedicated committees composed of ESMO officers and is directly supervised by the ESMO Executive Board and the ESMO President. It offers unique resources for YOs at all stages of training and includes a broad variety of fellowship opportunities, educational courses, scientific meetings, publications and resources. In this article, we provide an overview of the activities and career development opportunities provided by ESMO to the next generation of oncologists., Competing Interests: Competing interests: None declared.

The incidence of most gynaecological malignancies rises significantly with increasing age. With an ageing population, the proportion of women over the age of 65 with cancer is expected to rise substantially over the next decade. Unfortunately, survival outcomes are much poorer in older patients and evidence suggests that older women with gynaecological cancers are less likely to receive current standard of care treatment options. Despite this, older women are under-represented in practice changing clinical studies. The evidence for efficacy and tolerability is therefore extrapolated from a younger; often more fit population and applied to in every day clinical practice to older patients with co-morbidities. There has been significant progress in the development of geriatric assessment in oncology to predict treatment outcomes and tolerability however there is still no clear evidence that undertaking a geriatric assessment improves patient outcomes. Clinical trials focusing on treating older patients are urgently required. In this review, we discuss the evidence for treatment of gynaecological cancers as well as methods of assessing older patients for therapy. Potential biomarkers of ageing are also summarised., (Copyright © 2016. Published by Elsevier Ltd.)

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine apart from the revival of immunotherapy, requiring specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies., Competing Interests: JBe received research support to Karolinska Institutet and University Hospital from Amgen, AstraZeneca, Bayer, Merck, Roche and Sanofi-Aventis. JBu received travel accommodations from Genentech/Roche. FC received a consultant honoraria in Astellas/Medivation, AstraZeneca, Celgene, Daiitchi-Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline (GSK), Merck-Scharp, Merus BV, Novartis, Pfizer, Pierre-Fabre, Roche, Sanofi, Teva. HC has worked in a consulting or advisory role in Amgen received speakers’ bureau in Baxalta, Celgene and received research funding from Celgene. PC received honoraria for consultancy/advisory role and/or for lectures from Bayer, Blueprint Medicines, Eisai, Eli Lilly, Glaxo SK, Merck SD, Merck Serono, Nektar Ther., Novartis, Pfizer, PharmaMar. AC received honoraria from MerckSerono, Roche, Amgen, Bayer, Lilly and speakers’ bureau from Roche and MerckSerono. RC received research funding from Genentech/Roche, Puma Biotechnology, Novartis and travel, accommodations, expenses from Novartis. LDP received fees as consultant or for lectures (no speakers’ bureau) from F. Hoffmann-La Roche, Pfizer, Bristol Meyer Squibb, AstraZeneca, Qiagen, Boehringer Ingelheim. All fees were paid to Institution. MDS received honoraria and consultation fees from Amgen, Astellas, Bayer, Celgene, Dendreon, Eisai Inc, ESSA, Ferring, GSK, Janssen Cilag, Merck, Novartis, Pfizer, Pierre Fabre Oncologie, Roche, Sanofi Aventis, Shionogi, Synthon, Takeda, Teva/OncoGenex; received research grant from Pierre Fabre Oncologie. EGEdV received research grants to the institute from Roche/Genentech, Amgen, Novartis, Pieris, Servier, is part of data monitoring committee in Biomarin and of advisory board in Synthon. CD received (un)restricted research grants donated to the research institute from Amgen, AstraZeneca, Bayer, Celgene, Eisai, Boehringer Ingelheim, Merck, MSD, Mundipharma, Novartis, Pfizer Corporation, PharmaMar, Pierre Fabre, Roche Austria, Sanofi-aventis, Takeda; received honoraria for consulting from AstraZeneca, Eli Lilly, Merck, Novartis Pharma, Roche Austria. DSD has worked in a consulting or advisory role for UpToDate and received research funding from Aeterna Zentaris (to Institution). LRD received research funding from GlaxoSmithKline (to Institution), Millennium (to Institution), Bristol-Myers Squibb (to Institution), Aeterna Zentaris (to Institution), Millenuim (to Institution) and has other relationship with Genentech. NES received honoraria from Roche, Novartis, MSD Oncology; received research funding from GlaxoSmithKline, Roche; received travel, accommodations, expenses from Novartis, Roche, Celgene. AE conduct research sponsored by Roche, GSK, Novartis, AstraZeneca, Celltrion, Apotex Inc. ME has stock and other ownership interests with Bristol-Myers Squibb, GE Healthcare, Nestle SA, Pfizer, CVS CAREMARK; has worked in a consulting or advisory role from Merck, Bristol-Myers Squibb, ALKERMES; received research funding from Altor BioScience, Bristol-Myers Squibb, Merck, Alkermes, Polynoma; received travel, accommodations, expenses from Myriad Genetics, Bristol-Myers Squibb, Merck. EF has worked as a consultant for Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, BMS, MSD, Novartis; received speaker's bureau from Eli Lilly, BMS, Novartis. MFF has owned stock from Novartis. PKG research funding from Abbvie (to Institution) and Onyx (to Institution). AG has worked in a consulting or advisory role for Genentech/Roche (to Institution), Bayer (to Institution), Sanofi (to Institution), Bristol-Myers Squibb (to Institution), Lilly (to Institution), Boston Biomedical (to Institution), Amgen (to Institution); received research funding from Genentech/Roche (to Institution), Bayer (to Institution), Pfizer (to Institution), Eisai (to Institution), Sanofi (to Institution), Lilly (to Institution), Boston Biomedical (to Institution); received travel, accommodations, expenses from Genentech/Roche, Bayer, Bristol-Myers Squibb, Boston Biomedical, Amgen. SMH has stock and other ownership interests with Liquid Biotech, USA; has patents, royalties, other intellectual property with Liquid Biotech, USA. JH received advisory board and speaker fee from Tesaro and honorarium from SOBI. DVJ has worked in a consulting or advisory role for Bayer. UK received honoraria from Amgen, BMS, GSK, Glycotope, MerckSerono, Merck/MSD, Pfizer; received research support from Pfizer, MerckSerono, Innate, Sirtec. RK conduct research supported by Roche; a member of speaker's bureau of Roche, Meda, Novartis. SK received research funding from Novartis (to Institution), Merck (to Institution), Threshold Pharmaceuticals (to Institution), Gilead Sciences (to Institution), Bayer/Onyx (to Institution); received travel, accommodation, expenses from Novartis. C-HK received honoraria from Merck/Darmstadt, Amgen. MK is on speakers’ bureau for Astellas Pharma, Genentech/Roche, Sanofi, Lilly, Bayer; received research funding from Genentech/Roche (to Institution) and Merck Serono (to Institution). H-JL has received honoraria from Merck Serono, Roche, Celgene, Bayer, Boehringer Ingelheim; has served in a consulting or advisory role for Merck Serono, Roche, Bayer; received travel, accommodations, expenses from Merck Serono, Bayer, Roche. LL has served as a consultant/advisory for EISAI, BMS, MSD, Merck-Serono, Boehringer Ingelheim, DEBIOPHARM, SOBI, Novartis, AstraZeneca, Bayer and Roche; received research funds to institute for clinical studies from EISAI, MSD, Merck-Serono, Boehringer Ingelheim, Novartis, AstraZeneca and Roche; received travel coverage for medical meetings from Merck-Serono, DEBIOPHARM, SOBI, Bayer. PJL received research funding from Novartis (to Institution), Celgene (to Institution), ImClone Systems (to Institution), Taiho Pharmaceutical (to Institution); has patents, royalties, other intellectual property US PPA/61/499,988 Gene Expression Analysis of Thymic Neoplasms Inventors Sunil Badve, Yesim Gokmen-Polar, Patrick Loehrer (to Institution). RIL has served in consulting or advisory role for Roche, Novartis, Janssen; received speakers’ bureau from Roche, Novartis, Janssen. MJM received research funding from Astex Pharmaceuticals (to Institution). TN has ownership interest with Bioclassifier LLC; has role for invention of PAM50 breast cancer assay, which has been licensed to NanoString technologies and being marketed as Prosigna; has served as a consultant for NanoString. KÖ received speaker bureau from Novartis, Ipsen. PÖ received consulting fees, honoraria, travel grants or lecturing fees from Amgen, Bayer, Baxalta, Celgene, EliLilly, Merck, Nordic Drugs, Prime Oncology, Sanofi Oncology. AP received honoraria and consultancy fee from Amgen, Novartis, Bristol-Myers Squibb, Genmab A/S, Celgene, Janssen-Cilag, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Sanofi Aventis. MR received honoraria from AstraZeneca; has served in a consulting or advisory role for Bayer, Pfizer, McKesson; received research funding from AstraZeneca (to Institution), AbbVie (to Institution), Myriad Genetics (to Institution), Biomarin (to Institution); received travel, accommodations, expenses from AstraZeneca, Biomarin. LS has served in a consulting or advisory role for bioTheranostics. MS conduct research sponsored by AstraZeneca, Bayer, Eisai, Exelixis, Genzyme. H-JS is an advisor for Roche, Bayer. LS has served in leadership for Eviti; has served in a consulting or advisory role for Merck; has patents, royalties, other intellectual property; as Co-Editor-in-Chief of UpToDate, Oncology. JS is an employee of Genentech; received honoraria, speakers’ bureau, travel, accommodations, expenses from Genentech. CNS received honoraria or research grant from Novartis, GSK, Pfizer, Merck, Lilly, BMS, Astellas, Bayer, Janssen, Sanofi. FS received unrestricted industry grants for clinical research from Celgene, Fresenius, Helsinn; FS participates in Novartis-lead clinical trials and received punctual advisorship (boards, expert meetings) from Acacia, ACRAF, Amgen, Baxter, Celgene, Danone, Fresenius, GlaxoSmithKline, Grünenthal, Helsinn, ISIS Global, Millennium/Takeda, Mundipharma, Novartis, Novelpharm, Nycomed, Obexia, Otsuka, Ono, Pharm-Olam, Pfizer, Psioxus, PrIME, Santhera, Sunstone, Teva, Vifor. RS received honoraria or consulting fee (paid to institution) from Roche, Merck KGaA/EMD-Serono, MSD/Merck & Co, Pfizer, Ipsen Pharma, Novartis. JT has worked in a consultant/advisory role for Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Symphogen, Taiho and Takeda. EV has stock and other ownership interests with McKesson; has worked in a consulting or advisory role for Abbvie, AstraZeneca, Boehringer Ingelheim, Celgene, Clovis Oncology, GeneCentric, Genentech, Merck, Synta, VentiRx, Eisai, Lilly, Transgene; received speakers’ bureau for Amgen; received research funding from Abbvie (to Institution), Bristol-Myers Squibb (to Institution), Gen Vec Inc, (to Institution), Sanofi (to Institution), Monsanto (to Institution), Cyclacel (to Institution); received travel, accommodations, expenses from Amgen. JSW has stock and other ownership interests with Altor BioScience, Celldex, cCam Biotherapeutics; received honoraria from Bristol-Myers Squibb, Merck, Genentech, Abbvie, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Eisai, Altor BioScience, Lion Biotechnologies, Amgen, Roche, Ichor Medical Systems, Celldex, cCam Biotherapeutics, Pieris; has worked in a consulting or advisory role for Celldex, Ichor Medical Systems, cCam Biotherapeutics, Lion Biotechnologies, Pieris, Altor BioScience, Bristol-Myers Squibb, Merck, Genentech, Roche, Amgen, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, Abbvie, Eisai; received research funding from Bristol-Myers Squibb (to Institution), Merck (to Institution), GlaxoSmithKline (to Institution), Genentech (to Institution), Astellas Pharma (to Institution), Incyte (to Institution), Roche (to Institution), Novartis (to Institution); received travel, accommodations, expenses from Bristol-Myers Squibb, GlaxoSmithKline, Daiichi Sankyo, Pieris, cCam Biotherapeutics, Lion Biotechnologies, Roche, Celldex, Amgen, Merck, AstraZeneca, Genentech.

Despite effective treatments for oestrogen receptor-positive breast cancers, drug resistance is common and remains a significant clinical challenge. Targeting tumour vasculature by blockade of the vascular endothelial growth factor (VEGF) has proved successful in a variety of cancers. Phase III clinical trials of bevacizumab in combination with chemotherapy showed some efficacy in breast cancer. Concomitant targeting of the VEGF and oestrogen signalling pathways has the potential to provide enhanced therapeutic benefit in oestrogen receptor-positive breast cancer, and this strategy is under evaluation in clinical trials. This article summarises the rationale for this approach and clinical studies so far., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Survival rates for metastatic colorectal cancer (CRC) have increased considerably over the years largely because of the application of optimized chemotherapy regimens. More recently, the addition of the targeted agents bevacizumab, cetuximab, and panitumumab in advanced disease has also demonstrated clinical benefit. Adjuvant chemotherapy is the standard of care in patients with early-stage CRC who are at high risk of recurrence. One challenge is how to apply targeted agents in early-stage CRC. Initial results from the NSABP-08 trial in CRC, the first report of bevacizumab in the adjuvant treatment of solid cancers, are disappointing. Nevertheless, the results of several important phase III trials of targeted adjuvant therapy are awaited. Until then, the use of targeted agents in early-stage CRC cannot be recommended. The identification of biomarkers to select patients who might derive clinical benefit is crucial in determining the full potential of targeted agents in the adjuvant setting. In this review, we discuss the biologic rationale for targeted therapies in early-stage CRC, the current clinical trials, and the clinical challenges facing the success of these agents in the adjuvant setting.