3. Administration of olaparib or placebo continued for up to 24 months from randomization or until disease progression (according to investigators assessment of imaging based on the modified Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) or unacceptable toxic effects, whichever occurred first, as long as the patient had a benefit and did not meet other discontinuation criteria. (For details on the FIGO staging system, see Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org.) The most common serious adverse event that occurred at a higher incidence with olaparib plus bevacizumab than with placebo plus bevacizumab was anemia (34 patients [6%] in the olaparib group and 1 patient [<1%] in the placebo group). Randomization was performed centrally with the use of a block design with stratification according to the outcome of first-line treatment at screening and tumor BRCA status (see the Supplementary Appendix). From Centre Lon Brard (I.R.-C., D.P. The median duration of follow-up for the primary analysis was 22.7 months (range, 18.0 to 27.7) in the olaparib group and 24.0 months (range, 18.7 to 27.7) in the placebo group; the median duration of follow-up in the combined groups was 22.9 months. The median duration of treatment with bevacizumab since randomization was 11.0 months (range, 0.7 to 21.4) in the olaparib group and 10.6 months (range, 0.7 to 17.1) in the placebo group. Stat Med 1997;16:2349-2380. In an interim analysis of second progressionfree survival (data maturity, 39%), the KaplanMeier estimate of the rate of freedom from second disease progression and death at 18 months was 79% in the olaparib group and 80% in the placebo group (hazard ratio, 0.86; 95% CI, 0.69 to 1.09) (Fig. Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. NEW! ), German Society of Gynecologic Oncology (AGO) (J.S., U.C., F.M., N.G., P.B., A.B., P.H. Mirza MR, Avall-Lundqvist E, Birrer MJ, et al. All efficacy data were summarized and analyzed in the intention-to-treat population, which included all the patients who had undergone randomization, regardless of the intervention received. ), Institut Curie, Hpital Claudius Rgaud (M.R. 16. (Data for patients whose tumor HRD status was unknown are shown in Fig. ); and CharitMedical University of Berlin (Campus Virchow Klinikum), Berlin (J.S. A total of 30% of the patients had stage IV disease, and most patients had no evidence of disease owing to complete cytoreduction or were having a complete response after first-line treatment.

Unknown was defined as an inconclusive, missing, or failed test. Ledermann J, Harter P, Gourley C, et al. The data include patients with thrombocytopenia, decreased platelet production, a decreased platelet count, or a decreased plateletcrit. The most advanced way to teach, practice, and assess clinical reasoning skills. The median time until the first subsequent treatment for all patients was 24.8 months in the olaparib group and 18.5 months in the placebo group (hazard ratio, 0.59; 95% CI, 0.49 to 0.71). Lancet Oncol 2017;18:1274-1284. Ann Oncol 2017;28:711-717. Oza AM, Cook AD, Pfisterer J, et al. Previously defined toxic effects of olaparib and bevacizumab were noted, and rare serious hematologic and mild-to-moderate pulmonary toxic effects also occurred. all in Japan; University Hospital Leuven, Leuven Cancer Institute, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG) both in Leuven, Belgium (I.V. The PAOLA-1 population was representative of the majority of patients with advanced ovarian cancer because patient selection was not restricted on the basis of surgical outcome or BRCA mutation status. La et Napolon Bullukian, Lyon 69008, France, or at [emailprotected]. S3A). 14. 21. In this trial, the progression-free survival benefit seen with olaparib plus bevacizumab in patients with BRCA-mutated tumors (hazard ratio for disease progression or death, 0.31; 95% CI, 0.20 to 0.47) is consistent with that observed in the SOLO1 trial (hazard ratio, 0.30; 95% CI, 0.23 to 0.41),8 despite the improved outcome of the control group in our trial (median progression-free survival, 21.7 months with placebo plus bevacizumab in the PAOLA-1 trial and 13.8 months with placebo in the SOLO1 trial), which may be due to the addition of bevacizumab or to differences in patient selection.22 Caution is needed when comparing outcomes between patients in the SOLO1 trial and patients with BRCA-mutated tumors in the PAOLA-1 trial because of differences between the two trials, including in baseline characteristics (Table S3). Grade 1 or 2 pneumonitis, interstitial lung disease, or bronchiolitis occurred in 6 patients (1%) in the olaparib group and no patients in the placebo group. The data include patients with a decreased lymphocyte count, lymphopenia, a decreased B-lymphocyte count, or a decreased T-lymphocyte count. Patients were eligible regardless of surgical outcome or BRCA mutation status. Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Among the patients with a tumor BRCA mutation (prespecified subgroup analysis) (Panel A), the KaplanMeier estimate of the percentage of patients who were free from disease progression and death at 24 months was 76% in the olaparib-plus-bevacizumab group and 39% in the placebo-plus-bevacizumab group. ), and Association de Recherche Cancers Gyncologiques (ARCAGY) (E.P.-L.), Paris, Gustave Roussy, Villejuif (P.P. The baseline characteristics were well balanced between the trial groups (Table 1 and Tables S2 through S4). Details of discontinuation criteria and methods for unblinding are provided in the Supplementary Appendix. Thrombocytopenia occurred in less than 10% of the patients in each trial group, but the data are provided to complete the profile of hematologic toxic effects. A phase 3 trial of bevacizumab in ovarian cancer. 11. ), Universittsklinikum Ulm, Ulm (N.G. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. ), University of MilanBicocca and European Institute of Oncology IRCCS, and Mario Negri Gynecologic Oncology Group (MANGO) (N.C.), and Fondazione IRCCS Istituto Nazionale Tumori and MITO (D.L.

Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 2015;16:928-936. Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. Ann Oncol 2019;30:551-557. Clinical complete response was defined as the disappearance of all measurable or assessable disease and normalization of CA-125 levels. N Engl J Med 2011;365:2473-2483. The authors attest to the accuracy and completeness of the data and to the adherence of the trial to the protocol (available at NEJM.org). Details of BRCA testing and full eligibility criteria are provided in the Supplementary Appendix. PARP inhibitors trap PARP on DNA at sites of single-strand breaks, preventing the repair of these breaks and generating double-strand breaks that cannot be repaired accurately in tumors with homologous-recombination deficiency (HRD).9 HRD is not limited to tumors with BRCA mutations and is present in approximately 50% of high-grade serous ovarian tumors.10 Indeed, in platinum-sensitive relapsed ovarian cancer,11-13 PARP inhibitors are active as maintenance monotherapy in patients who have tumors without BRCA mutations, although the magnitude of benefit appears lower than in patients with BRCA-mutated tumors. The hazard ratio and associated 95% confidence interval were calculated with the use of a stratified Cox proportional-hazards model. ), Universittsklinikum Essen (P.B. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644. In the phase 3 PAOLA-1 trial, we evaluated maintenance therapy with the PARP inhibitor olaparib as compared with placebo in patients with newly diagnosed advanced ovarian cancer who were receiving chemotherapy and bevacizumab followed by bevacizumab. Patients were eligible irrespective of previous surgical outcome (residual macroscopic disease or no residual macroscopic disease after upfront or interval surgery).

Details of trial end points and analyses are provided in the Supplementary Appendix. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. After discontinuation of the intervention, patients could receive other treatments at the investigators discretion. NEW! ), Universittsklinikum Heidelberg, Heidelberg (F.M. Myelodysplastic syndromes, acute myeloid leukemia, or aplastic anemia occurred in 6 of 535 patients (1%) receiving olaparib plus bevacizumab and in 1 of 267 patients (<1%) receiving placebo plus bevacizumab. The trial met its primary objective by showing a significant progression-free survival benefit in the intention-to-treat population. All the patients provided written informed consent. ), Gynecologic Oncology Trial and Investigation Consortium (GOTIC), Moroyama-cho (K.F., S.N. Tumor assessment scans (computed tomography or magnetic resonance imaging) were performed at baseline and then every 24 weeks (or at planned visits every 12 weeks if there was evidence of clinical progression or progression according to the serum level of cancer antigen 125) up to month 42 or until the date of data cutoff. Supported by Association de Recherche Cancers Gyncologiques (ARCAGY) Research, AstraZeneca, Merck Sharp & Dohme (a subsidiary of Merck), and F. HoffmannLa Roche. ), and Klinikum der Universitt Mnchen, Munich (A.B.) Cancer Res 2010;70:8045-8054. A hierarchical-testing procedure was used to control for type I error at 5% for progression-free survival, second progressionfree survival, and overall survival, in that order. Address reprint requests to Dr. Ray-Coquard at Centre Lon Brard, 28 Prom. In patients with HRD-negative tumors (277 patients), the median progression-free survival was 16.6 months in the olaparib group and 16.2 months in the placebo group (hazard ratio for disease progression or death, 1.00; 95% CI, 0.75 to 1.35) (Fig. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The PAOLA-1 population was representative of the majority of patients with advanced ovarian cancer because patient selection was not restricted on the basis of surgical outcome or, The lack of a maintenance olaparib monotherapy comparator group is a limitation of the PAOLA-1 trial, making it difficult to conclude whether the progression-free survival benefit seen in patients with HRD-positive tumors without, Case Records of the Massachusetts General Hospital, Monkeypox Virus Infection in Humans across 16 Countries AprilJune 2022, Protection Associated with Previous SARS-CoV-2 Infection in Nicaragua, Nirmatrelvir for Nonhospitalized Adults with Covid-19, Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants, Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age, Evidence for Step Therapy in Diabetic Macular Edema, Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults, Case 23-2022: A 49-Year-Old Man with Hypoglycemia, Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus, Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkins Lymphoma, NEJM Catalyst Innovations in Care Delivery.

Ledermann JA, Harter P, Gourley C, et al. The addition of olaparib to bevacizumab did not increase the known toxic effects associated with bevacizumab. Vergote I, Pujade-Lauraine E, Pignata S, et al. Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. Analyses of health-related quality of life used an imputation-based approach for missing questionnaires. The authors wrote the manuscript, with medical writing assistance funded by ARCAGY Research, AstraZeneca, and Merck Sharp & Dohme. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Incorporation of bevacizumab in the primary treatment of ovarian cancer. Lancet Oncol 2016;17:1579-1589. Other was defined as clear-cell (in 2 patients assigned to olaparib plus bevacizumab), undifferentiated (in 1 patient assigned to olaparib plus bevacizumab and 6 patients assigned to placebo plus bevacizumab), or other (in 3 patients assigned to olaparib plus bevacizumab and 2 patients assigned to placebo plus bevacizumab). Cnaan A, Laird NM, Slasor P. Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Among the patients with HRD-positive tumors, as defined by a tumor HRD score of 42 or higher or a tumor BRCA mutation (prespecified subgroup analysis) (Panel C), the KaplanMeier estimate of the percentage of patients who were free from disease progression and death at 24 months was 66% in the olaparib-plus-bevacizumab group and 29% in the placebo-plus-bevacizumab group. Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. ), Hpital Europen Georges Pompidou (P.C. Moreover, the addition of an antiangiogenic agent to a PARP inhibitor in phase 2 studies involving patients with relapsed platinum-sensitive ovarian cancer14-16 resulted in longer progression-free survival than the use of a PARP inhibitor alone. In patients with HRD-negative tumors or whose tumor HRD status was unknown (total, 419 patients), the median progression-free survival was 16.9 months in the olaparib group and 16.0 months in the placebo group (hazard ratio for disease progression or death, 0.92; 95% CI, 0.72 to 1.17) (Fig. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. Colombo N, Sessa C, du Bois A, et al. *Data are shown for adverse events that occurred in at least 10% of the patients in either trial group (except where noted) during the trial intervention or up to 30 days after discontinuation of the intervention. Gynecol Oncol 2014;132:8-17. 8. all in Germany. Nature 2011;474:609-615. Among the patients with HRD-positive tumors without a BRCA mutation (prespecified subgroup analysis) (Panel D), the KaplanMeier estimate of the percentage of patients who were free from disease progression and death at 24 months was 52% in the olaparib-plus-bevacizumab group and 26% in the placebo-plus-bevacizumab group. S4).

Safety data were summarized in the safety analysis set (all patients who received at least one dose of olaparib or placebo). all in Austria; Saitama Medical University International Medical Center, Hidaka (K.F. Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. We conducted a randomized, double-blind, international phase 3 trial. 7. Integrated genomic analyses of ovarian carcinoma. Clin Cancer Res 2018;24:777-783. From July 2015 through September 2017, a total of 806 patients underwent randomization. 15. ), Essen, Universittsklinikum Carl Gustav Carus, Technische Universitt Dresden, Dresden (U.C. CA-125 denotes cancer antigen 125, and HRD homologous-recombination deficiency. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. The primary end point was the time from randomization until investigator-assessed disease progression or death. Patients were eligible irrespective of previous surgical outcome (residual macroscopic disease or no residual macroscopic disease after upfront or interval surgery). CA-125 denotes cancer antigen 125, CR complete response, ECOG Eastern Cooperative Oncology Group, FIGO International Federation of Gynecology and Obstetrics, NED no evidence of disease, PR partial response, and ULN upper limit of the normal range. Stay connected to what's important in medical research and clinical practice, Subscribe to the most trusted and influential source ofmedical knowledge. Subgroup analyses of progression-free survival and a blinded independent central review of progression-free survival were performed. Crossover between the trial groups was not planned.

The most trusted, influential source of new medical knowledge and clinical best practices in the world. ), Health Services and Performance Research Lab (EA 7425 HESPER), University Claude Bernard Lyon 1 (I.R.-C.), and Centre Hospitalier Lyon-Sud (B.Y. Patients were assigned to olaparib tablets or matching placebo tablets with the use of an interactive Web or voice response system. Valuable tools for building a rewarding career in health care.

OConnor MJ. The outcome of first-line treatment at screening was determined according to the electronic case-report form. Adverse events were usually managed by dose modification rather than discontinuation (Table 2). N Engl J Med 2016;375:2154-2164. 25. The most common adverse events and the incidence of associated grade 3 or higher adverse events for the entire maintenance treatment period are shown in Table 2 and Table S5. J Clin Oncol 2019;37:2317-2328. According to KaplanMeier estimates, the percentage of patients in the olaparib-plus-bevacizumab group and the placebo-plus-bevacizumab group who were free from disease progression and death was 78% and 66%, respectively, at 12 months; 62% and 46%, respectively, at 18 months; and 46% and 28%, respectively, at 24 months. The data include patients with neutropenia, febrile neutropenia, neutropenic sepsis, neutropenic infection, a decreased neutrophil count, idiopathic neutropenia, granulocytopenia, a decreased granulocyte count, or agranulocytosis. ), and Hyogo Cancer Center, Akashi (S.N.) In the phase 3 PAOLA-1 (PAOLA-1/ENGOT-ov25) trial, we evaluated maintenance therapy with a PARP inhibitor (olaparib) as compared with placebo in patients with newly diagnosed advanced ovarian cancer who were receiving chemotherapy plus bevacizumab followed by bevacizumab, regardless of BRCA mutation status. Patients with other nonmucinous epithelial ovarian cancers were eligible, provided they had a deleterious germline BRCA1 or BRCA2 mutation. The lack of a maintenance olaparib monotherapy comparator group is a limitation of the PAOLA-1 trial, making it difficult to conclude whether the progression-free survival benefit seen in patients with HRD-positive tumors without BRCA mutations (who were not included in the SOLO1 trial) was due largely to the addition of olaparib or whether a synergistic effect occurred with olaparib and bevacizumab. Liu JF, Barry WT, Birrer M, et al. Eastern Cooperative Oncology Group (ECOG) performance status ranges from 0 to 5, with higher values reflecting greater disability. 6. AstraZeneca, Merck Sharp & Dohme (a subsidiary of Merck), and F. HoffmannLa Roche were given the opportunity to review drafts of the manuscripts but were not asked to approve the final content because this was an academic-sponsored trial. 2. 5. In this analysis, we used the electronic case-report form data set, except for the prespecified HRD analysis, which used the Myriad myChoice Plus HRD test. In patients with a tumor BRCA mutation, the median progression-free survival was 37.2 months in the olaparib group and 21.7 months in the placebo group (hazard ratio for disease progression or death, 0.31; 95% CI, 0.20 to 0.47) (Figure 3A). NA denotes not available. A benefit was also seen in patients whose tumor HRD status was unknown, such as those with failed tests or insufficient tumor samples. The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). ), Milan, and Fondazione Policlinico Universitario A. Gemelli IRCCS, Universit Cattolica, and MITO, Rome (G.S.) The most common adverse events leading to discontinuation of olaparib were anemia and nausea (Table S7). A total of 535 of the 537 patients assigned to olaparib plus bevacizumab (olaparib group) and 267 of the 269 patients assigned to placebo plus bevacizumab (placebo group) received the trial intervention; 2 patients in each group withdrew before receiving the trial intervention (Fig. Administering maintenance olaparib in addition to bevacizumab to patients with newly diagnosed advanced ovarian cancer who were receiving standard treatment including bevacizumab resulted in a significant progression-free survival benefit, with a substantial benefit in patients with HRD-positive tumors. Anderson Cancer Center Madrid (A.G.-M.), Grupo Espaol de Investigacin en Cncer de Ovario (GEICO) (A.G.-M., E.M.G.A. Dr. Ray-Coquard reports receiving consulting fees and travel support from Roche and AstraZeneca, consulting fees from PharmaMar, Genmab, Pfizer, Tesaro, and Clovis Oncology, and grant support and consulting fees from Merck Sharp & Dohme; Dr. Pautier, receiving advisory board fees from AstraZeneca; Dr. Pignata, receiving honoraria from AstraZeneca, Roche, Merck Sharp & Dohme, Pfizer, Tesaro, Clovis Oncology, and PharmaMar; Dr. Prol, receiving fees for training and advisory fees from Roche, fees for training, advisory fees, and travel support from AstraZeneca, and grant support from MSDAVENIR; Dr. Gonzlez-Martn, receiving consulting fees, lecture fees, and travel support from AstraZeneca and PharmaMar, grant support, consulting fees, lecture fees, and travel support from Tesaro and Roche, and consulting fees from Clovis Oncology, Merck Sharp & Dohme, Pfizer, ImmunoGen, Genmab, and Novartis; Dr. Berger, receiving travel support from Roche, Merck, Biocad, Clovis Oncology, and Advaxis, lecture fees and travel support from AstraZeneca, and advisory board fees from PharmaMar; Dr. Fujiwara, receiving grant support from Kaken Pharmaceutical, Shionogi, GlaxoSmithKline, Eli Lilly, ImmunoGen, OncoTherapy Science, and Regeneron Pharmaceuticals, grant support and consulting fees from Pfizer, Eisai, and Taiho, grant support, consulting fees, and honoraria from Merck Sharp & Dohme, grant support and honoraria from Zeria Pharmaceutical, and honoraria from Nippon Kayaku, Kyowa Hakko Kirin, Janssen, Daiichi Sankyo, and Mochida Pharmaceutical; Dr. Vergote, receiving consulting fees, paid to his institution, from Advaxis, Eisai, Merck Sharp & Dohme Belgium, F. HoffmannLa Roche, Millennium Pharmaceuticals, Oncoinvent, and Sotio, consulting fees, paid to his institution, and travel support from Roche, Genmab, PharmaMar, Clovis Oncology, AstraZeneca, Tesaro, and ImmunoGen, grant support, paid to his institution, from Amgen, Stichting tegen Kanker, and Roche, research support from Oncoinvent and Genmab, and travel support from Takeda Oncology; Dr. Colombo, receiving advisory board fees from Roche, Clovis Oncology, Pfizer, Merck Sharp & Dohme, Biocad, ImmunoGen, and Takeda and advisory board fees and lecture fees from AstraZeneca, Tesaro, and PharmaMar; Dr. Menp, receiving consulting fees from AstraZeneca, Clovis Oncology, Merck Sharp & Dohme, and Orion Pharma and consulting fees and travel support from Roche and Tesaro; Dr. Selle, receiving consulting fees, lecture fees, fees for serving on a speakers bureau, and travel support from Roche, lecture fees, fees for serving on a speakers bureau, and travel support from AstraZeneca, Tesaro, and PharmaMar, lecture fees from Clovis Oncology, and lecture fees and travel support from Merck Sharp & Dohme; Dr. Sehouli, receiving advisory board fees and travel support from AstraZeneca and grant support, advisory board fees, and travel support from Clovis Oncology, Tesaro, and Roche; Dr. Lorusso, receiving grant support and advisory board fees from ImmunoGen, Genmab, PharmaMar, Clovis Oncology, Tesaro, Merck, and AstraZeneca; Dr. Guerra Ala, receiving consulting fees, advisory board fees, and travel support from Roche, consulting fees and advisory board fees from Clovis Oncology, Tesaro, PharmaMar, AstraZeneca, Merck Sharp & Dohme, and GlaxoSmithKline, and travel support from Baxter and GlaxoSmithKline/Tesaro; Dr. Reinthaller, receiving grant support, lecture fees, advisory board fees, and travel support from Roche, lecture fees, advisory board fees, and travel support from Amgen, AstraZeneca, PharmaMar, and Tesaro, and lecture fees and advisory board fees from Merck Sharp & Dohme and Vifor Pharma; Dr. Nagao, receiving grant support from PFDeNA, Tosoh, and Toray and lecture fees from Chugai, AstraZeneca, Mochida Pharmaceutical, and Asahi Kasei Medical; Dr. Lefeuvre-Plesse, receiving advisory board fees from AstraZeneca and participating in a medical congress for Novartis, Pfizer, Roche, and Pierre Fabre; Dr. Canzler, receiving honoraria from AstraZeneca, Roche, and Eli Lilly; Dr. Scambia, receiving honoraria from AstraZeneca, Tesaro, and Roche; Dr. Lortholary, receiving advisory board fees from AstraZeneca and participating in a medical congress for Novartis, Pfizer, and Roche; Dr. Marm, receiving fees for serving as principal investigator of a clinical trial, advisory board fees, and lecture fees from Pfizer, Tesaro, and Novartis, advisory board fees and lecture fees from Amgen, PharmaMar, Genomic Health, Eisai, and Celgene, advisory board fees from CureVac and Janssen-Cilag, and advisory board fees, paid to his institution, from Immunomedics; Dr. de Gregorio, receiving advisory fees from Roche, PharmaMar, and Amgen and advisory fees and travel support from AstraZeneca and Tesaro; Dr. Rodrigues, receiving travel support from F. HoffmannLa Roche, advisory board fees and lecture fees from AstraZeneca, advisory board fees and travel support from Tesaro, and grant support from Bristol-Myers Squibb and Merck; Dr. Buderath, receiving advisory board fees and travel support from Roche and travel support from PharmaMar; Dr. Burges, receiving consulting fees and lecture fees from AstraZeneca, Tesaro, and Roche; Dr. You, receiving consulting fees, advisory board fees, and travel support from and participating in a medical congress for AstraZeneca, Merck Sharp & Dohme, and Bayer and receiving consulting fees and advisory board fees from Tesaro, Clovis Oncology, Amgen, Novartis, Roche, and ECS Progastrin; Dr. Pujade-Lauraine, receiving lecture fees, fees for serving on a speakers bureau, and travel support from AstraZeneca, Tesaro, and Roche, receiving lecture fees from Clovis Oncology, Incyte, and Pfizer, and being employed by ARCAGY Research; and Dr. Harter, receiving consulting fees from Sotio, Merck Sharp & Dohme, Clovis Oncology, and ImmunoGen, grant support, consulting fees, and lecture fees from Tesaro, AstraZeneca, and Roche, lecture fees from Stryker and Zai Lab, and grant support from GlaxoSmithKline, Boehringer Ingelheim, Medac, Genmab, and Deutsche Forschungsgemeinschaft.



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