- Email: [email protected]
Neoadjuvant olaparib monotherapy in primary triple negative breast cancer
abstracts Clinical trial identification: NCT02624973; 2015-002816-34. Legal entity responsible for the study: Haukeland University Hospital, Bergen, Norway. Funding: Det Regionale Samarbeidsorganet/Helse Vest, Pfizer. Disclosure: P.E. Lønning: Honoraria (self), Advisory / Consultancy, Research grant / Funding
184PD
Neoadjuvant olaparib monotherapy in primary triple negative breast cancer
H.P. Eikesdal1, S. Yndestad2, E.S. Blix3, S. Lundgren4, G. Vagstad5, H. Espelid6, B. Gilje7, E.A. Janssen8, J. Geisler9, T. Aas10, H. Aase11, S. Knappskog2, P.E. Lønning1 1 Department of Oncology, Haukeland University Hospital, Bergen, Norway, 2Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway, 3 Department of Oncology, University Hospital of North Norway, Tromsø, Norway, 4 Department of Oncology, St.Olavs University Hospital, Trondheim, Norway, 5 Department of Oncology, Førde Hospital, Førde, Norway, 6Department of Surgery, Haugesund Hospital, Haugesund, Norway, 7Department of Oncology, Stavanger University Hospital, Stavanger, Norway, 8Department of Pathology, Stavanger University Hospital, Stavanger, Norway, 9Institute of Clinical Medicine, University of Oslo, Akershus, Norway, 10Department of Surgery, Haukeland University Hospital, Bergen, Norway, 11Department of Radiology, Haukeland University Hospital, Bergen, Norway Background: Neoadjuvant treatment of triple negative breast cancer (TNBC) in general implies different chemotherapy regimens administered in sequence. PARP inhibitors like olaparib have revealed clinical benefit in TNBC harboring BRCA germline mutations, but were ineffective when tested as monotherapy for BRCA WT metastatic breast cancer. While combining a PARP inhibitor with chemotherapy may be beneficial, such therapy is limited by bone marrow toxicity. Methods: In the phase 2 PETREMAC trial (NCT02624973), we assessed the efficacy of primary olaparib monotherapy for 10 weeks, followed by chemotherapy, in TNBC (T > 2 cm). Tumor biopsies and blood leucocytes for targeted DNA sequencing of 360 cancer-related genes were collected prior to therapy and after 10 weeks on olaparib. Results: 31 patients with TNBC were included (mean tumor size 59 mm; range 33-97). Olaparib monotherapy was well tolerated, yielding a clinical CR in 5 and a PR in 15 patients (all-over objective response rate; ORR 64%). Olaparib had no major impact on subsequent chemotherapy toxicity. The average pretreatment mutation rate was 3.3 indels/point mutations per tumor with no differences in mutation burden recorded between responders and non-responders or BRCA carriers vs. non-carriers. Among five patients harboring pathogenic BRCA1/2 mutations (4 germline, 1 somatic) all responded to olaparib, and n ¼ 3/5 obtained pathological complete response. Interestingly, mutations in genes associated with DNA damage repair (ATRX, BRCA1/ 2, EMSY, MSH6, PARP10, PPM1D) occurred in n ¼ 9/20 olaparib responders, but in none of the 11 non-responders (p ¼ 0.011). Non-responders were characterized by mutations in oncogenic pathways (PIK3CA, AKT1, KRAS, IGF2R, NF2 and TGFBR2) in 7 out of 11 tumors (P ¼ 0.00013). No significant association was observed between TP53 mutations (recorded in 23/31 tumors) and response to olaparib. Targeted DNA sequencing is ongoing for biopsies taken after 10 weeks of olaparib monotherapy; the results will be presented. Conclusions: Olaparib yielded a high response rate when administered to treatmentnaı¨ve, large TNBC, indicating a potential role in sequential neoadjuvant therapy, for patients both with and without BRCA1/2 germline mutations. Clinical trial identification: NCT02624973; 2015-002816-34. Legal entity responsible for the study: Haukeland University Hospital, Bergen, Norway.
v60 | Breast Cancer, Early Stage
Funding: Det Regionale Samarbeidsorganet/Helse Vest, AstraZeneca. Disclosure: H.P. Eikesdal: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self): HAI Interaktiv AS; Honoraria (self): Dagens Medisin; Honoraria (self): BrysolMayers-Squibb; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Abbvie. E.S. Blix: Honoraria (self): Pfizer. B. Gilje: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Astellas Oncology; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Pierre Fabre. E.A. Janssen: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. J. Geisler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Speaker Bureau / Expert testimony: Brystol-Myers-Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer. T. Aas: Honoraria (self): AstraZeneca; Honoraria (self): Roche. S. Knappskog: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Licensing / Royalties: Patent EP2389450 A1,Patent WO 2012/010661.. P.E. Lønning: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Novartis; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Roche; Advisory / Consultancy: Laboratorios Farmaceuticos Rovi; Licensing / Royalties: Cytovation. All other authors have declared no conflicts of interest.
185PD
Immunological differences between immune-rich estrogen receptorpositive and -negative breast cancers
T. O’Meara1, M. Marczyk1, K. Blenman1, V. Yaghoobi2, V. Pelenkanou3, D. Rimm2, L. Pusztai4 1 Medical Oncology, Yale University School of Medicine, New Haven, CT, USA, 2 Pathology, Yale University School of Medicine, New Haven, CT, USA, 3Pathology, Sanofi, Cambridge, AL, USA, 4Medical Oncology, Yale University School of Medicine, New Haven, CT, USA Background: A subset of estrogen receptor-positive (ERþ) breast cancers have significant tumor infiltrating lymphocytes (TILs), similar to triple-negative breast cancer (TNBC). We examined differences in the immune microenvironment of immune-rich ERþ and immune-rich TNBC to find out if similar or different immunotherapy strategies are appropriate for these distinct disease types. Methods: ERþ/HER2-negative and TNBC cases were obtained from The Cancer Genome Atlas (TCGA) (n ¼ 818 RNA Seq) and METABRIC (n ¼ 1465 microarray). An immune gene expression score, as surrogate for TILs, was calculated for each case (Danaher et al). Signature scores were correlated with histologic TILs (R ¼ 0.44, p < 0.001) for available cases. All cases in the top 25% of signature scores were considered immune-rich. We compared 22 immune cell populations between immune-rich TNBC (n ¼ 86) and ER þ (n¼119) using CIBERSORT (Student’s t-test, FDR adjusted). We examined differential expression of 770 immune-related genes and 137 immunooncology (IO) drug targets. Macrophage abundance was measured by quantitative immunofluorescence (QIF) using pan-macrophage marker CD68 in 169 TNBC and 87 ERþ FFPE tissues. Results: In TCGA and METABRIC, CIBERSORT showed more M0 (p ¼ 0.015, p ¼ 0.0043) and M1 macrophages (p ¼ 9.4e-08, p ¼ 6.24e-11) in immune-rich TNBC compared to ERþ. Mast cells (p ¼ 0.0093, p ¼ 4.09e-15) and M2 macrophages (p ¼ 4.4e-05, p ¼ 0.053) were more abundant in immune-rich ERþ. QIF confirmed higher macrophage content in TNBC (p ¼ 0.0001). In both datasets, 36 IO targets were higher expressed in TNBC and 15 in ERþ cases (Table). Notably, coordinated high expression of TGFb pathway members TGFb3, TGFb-R2, and LRRC32 was seen in ERþ cancers and correlated positively with M2 and negatively with M1 macrophage content across all cases. Conclusions: IO drugs targeting TGFb, M2 macrophages and mast cells are attractive therapeutic candidates in immune-rich ERþ breast cancer based on the expression characteristics of these targets. Legal entity responsible for the study: The authors. Funding: Howard Hughes Medical Institute Medical Fellows Grant. Disclosure: V. Pelenkanou: Full / Part-time employment: Sanofi, US. D. Rimm: Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Agendia; Advisory / Consultancy: Biocept; Advisory / Consultancy: BMS; Advisory / Consultancy: Cell Signaling Technology; Advisory / Consultancy, Research grant / Funding (institution): Cepheid; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: GSK; Advisory / Consultancy: InVicro/Konica/Minolta; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): NanoString; Advisory / Consultancy, Research grant / Funding (institution): Perkin Elmer; Advisory / Consultancy: PAIGE.AI; Advisory / Consultancy, Research grant / Funding (institution): Ventana; Advisory / Consultancy, Research grant / Funding (institution): Ultivue; Shareholder / Stockholder / Stock options: PixelGear; Research grant / Funding (institution): Navigate/Novartis; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): Lilly. L. Pusztai: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self),
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.010/5577928 by guest on 26 October 2019
(institution): AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Roche; Advisory / Consultancy: Laboratorios Farmaceuticos Rovi; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Novartis; Licensing / Royalties: Cytovation. E.S. Blix: Honoraria (self): Pfizer. B. Gilje: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Astellas Oncology; Research grant / Funding (institution): Cellgene; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Pierre Fabre. E.A. Janssen: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. J. Geisler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Speaker Bureau / Expert testimony: Brystol-Myers-Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer. T. Aas: Honoraria (self): AstraZenaca; Honoraria (self): Roche. S. Knappskog: Honoraria (self), Research grant / Funding (institution): AstraZenaca; Honoraria (self), Research grant / Funding (institution): Pfizer; Licensing / Royalties: Patent EP2389450 A1,Patent WO 2012/010661. H.P. Eikesdal: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZenaca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self): HAI Interaktiv AS; Honoraria (self): Dagens Medisin; Honoraria (self): Brystol-Myers-Squibb; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Abbvie. All other authors have declared no conflicts of interest.
Annals of Oncology
184PD
Neoadjuvant olaparib monotherapy in primary triple negative breast cancer
H.P. Eikesdal1, S. Yndestad2, E.S. Blix3, S. Lundgren4, G. Vagstad5, H. Espelid6, B. Gilje7, E.A. Janssen8, J. Geisler9, T. Aas10, H. Aase11, S. Knappskog2, P.E. Lønning1 1 Department of Oncology, Haukeland University Hospital, Bergen, Norway, 2Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway, 3 Department of Oncology, University Hospital of North Norway, Tromsø, Norway, 4 Department of Oncology, St.Olavs University Hospital, Trondheim, Norway, 5 Department of Oncology, Førde Hospital, Førde, Norway, 6Department of Surgery, Haugesund Hospital, Haugesund, Norway, 7Department of Oncology, Stavanger University Hospital, Stavanger, Norway, 8Department of Pathology, Stavanger University Hospital, Stavanger, Norway, 9Institute of Clinical Medicine, University of Oslo, Akershus, Norway, 10Department of Surgery, Haukeland University Hospital, Bergen, Norway, 11Department of Radiology, Haukeland University Hospital, Bergen, Norway Background: Neoadjuvant treatment of triple negative breast cancer (TNBC) in general implies different chemotherapy regimens administered in sequence. PARP inhibitors like olaparib have revealed clinical benefit in TNBC harboring BRCA germline mutations, but were ineffective when tested as monotherapy for BRCA WT metastatic breast cancer. While combining a PARP inhibitor with chemotherapy may be beneficial, such therapy is limited by bone marrow toxicity. Methods: In the phase 2 PETREMAC trial (NCT02624973), we assessed the efficacy of primary olaparib monotherapy for 10 weeks, followed by chemotherapy, in TNBC (T > 2 cm). Tumor biopsies and blood leucocytes for targeted DNA sequencing of 360 cancer-related genes were collected prior to therapy and after 10 weeks on olaparib. Results: 31 patients with TNBC were included (mean tumor size 59 mm; range 33-97). Olaparib monotherapy was well tolerated, yielding a clinical CR in 5 and a PR in 15 patients (all-over objective response rate; ORR 64%). Olaparib had no major impact on subsequent chemotherapy toxicity. The average pretreatment mutation rate was 3.3 indels/point mutations per tumor with no differences in mutation burden recorded between responders and non-responders or BRCA carriers vs. non-carriers. Among five patients harboring pathogenic BRCA1/2 mutations (4 germline, 1 somatic) all responded to olaparib, and n ¼ 3/5 obtained pathological complete response. Interestingly, mutations in genes associated with DNA damage repair (ATRX, BRCA1/ 2, EMSY, MSH6, PARP10, PPM1D) occurred in n ¼ 9/20 olaparib responders, but in none of the 11 non-responders (p ¼ 0.011). Non-responders were characterized by mutations in oncogenic pathways (PIK3CA, AKT1, KRAS, IGF2R, NF2 and TGFBR2) in 7 out of 11 tumors (P ¼ 0.00013). No significant association was observed between TP53 mutations (recorded in 23/31 tumors) and response to olaparib. Targeted DNA sequencing is ongoing for biopsies taken after 10 weeks of olaparib monotherapy; the results will be presented. Conclusions: Olaparib yielded a high response rate when administered to treatmentnaı¨ve, large TNBC, indicating a potential role in sequential neoadjuvant therapy, for patients both with and without BRCA1/2 germline mutations. Clinical trial identification: NCT02624973; 2015-002816-34. Legal entity responsible for the study: Haukeland University Hospital, Bergen, Norway.
v60 | Breast Cancer, Early Stage
Funding: Det Regionale Samarbeidsorganet/Helse Vest, AstraZeneca. Disclosure: H.P. Eikesdal: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self): HAI Interaktiv AS; Honoraria (self): Dagens Medisin; Honoraria (self): BrysolMayers-Squibb; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Abbvie. E.S. Blix: Honoraria (self): Pfizer. B. Gilje: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Astellas Oncology; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Pierre Fabre. E.A. Janssen: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. J. Geisler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Speaker Bureau / Expert testimony: Brystol-Myers-Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer. T. Aas: Honoraria (self): AstraZeneca; Honoraria (self): Roche. S. Knappskog: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Licensing / Royalties: Patent EP2389450 A1,Patent WO 2012/010661.. P.E. Lønning: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Novartis; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Roche; Advisory / Consultancy: Laboratorios Farmaceuticos Rovi; Licensing / Royalties: Cytovation. All other authors have declared no conflicts of interest.
185PD
Immunological differences between immune-rich estrogen receptorpositive and -negative breast cancers
T. O’Meara1, M. Marczyk1, K. Blenman1, V. Yaghoobi2, V. Pelenkanou3, D. Rimm2, L. Pusztai4 1 Medical Oncology, Yale University School of Medicine, New Haven, CT, USA, 2 Pathology, Yale University School of Medicine, New Haven, CT, USA, 3Pathology, Sanofi, Cambridge, AL, USA, 4Medical Oncology, Yale University School of Medicine, New Haven, CT, USA Background: A subset of estrogen receptor-positive (ERþ) breast cancers have significant tumor infiltrating lymphocytes (TILs), similar to triple-negative breast cancer (TNBC). We examined differences in the immune microenvironment of immune-rich ERþ and immune-rich TNBC to find out if similar or different immunotherapy strategies are appropriate for these distinct disease types. Methods: ERþ/HER2-negative and TNBC cases were obtained from The Cancer Genome Atlas (TCGA) (n ¼ 818 RNA Seq) and METABRIC (n ¼ 1465 microarray). An immune gene expression score, as surrogate for TILs, was calculated for each case (Danaher et al). Signature scores were correlated with histologic TILs (R ¼ 0.44, p < 0.001) for available cases. All cases in the top 25% of signature scores were considered immune-rich. We compared 22 immune cell populations between immune-rich TNBC (n ¼ 86) and ER þ (n¼119) using CIBERSORT (Student’s t-test, FDR adjusted). We examined differential expression of 770 immune-related genes and 137 immunooncology (IO) drug targets. Macrophage abundance was measured by quantitative immunofluorescence (QIF) using pan-macrophage marker CD68 in 169 TNBC and 87 ERþ FFPE tissues. Results: In TCGA and METABRIC, CIBERSORT showed more M0 (p ¼ 0.015, p ¼ 0.0043) and M1 macrophages (p ¼ 9.4e-08, p ¼ 6.24e-11) in immune-rich TNBC compared to ERþ. Mast cells (p ¼ 0.0093, p ¼ 4.09e-15) and M2 macrophages (p ¼ 4.4e-05, p ¼ 0.053) were more abundant in immune-rich ERþ. QIF confirmed higher macrophage content in TNBC (p ¼ 0.0001). In both datasets, 36 IO targets were higher expressed in TNBC and 15 in ERþ cases (Table). Notably, coordinated high expression of TGFb pathway members TGFb3, TGFb-R2, and LRRC32 was seen in ERþ cancers and correlated positively with M2 and negatively with M1 macrophage content across all cases. Conclusions: IO drugs targeting TGFb, M2 macrophages and mast cells are attractive therapeutic candidates in immune-rich ERþ breast cancer based on the expression characteristics of these targets. Legal entity responsible for the study: The authors. Funding: Howard Hughes Medical Institute Medical Fellows Grant. Disclosure: V. Pelenkanou: Full / Part-time employment: Sanofi, US. D. Rimm: Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Agendia; Advisory / Consultancy: Biocept; Advisory / Consultancy: BMS; Advisory / Consultancy: Cell Signaling Technology; Advisory / Consultancy, Research grant / Funding (institution): Cepheid; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: GSK; Advisory / Consultancy: InVicro/Konica/Minolta; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): NanoString; Advisory / Consultancy, Research grant / Funding (institution): Perkin Elmer; Advisory / Consultancy: PAIGE.AI; Advisory / Consultancy, Research grant / Funding (institution): Ventana; Advisory / Consultancy, Research grant / Funding (institution): Ultivue; Shareholder / Stockholder / Stock options: PixelGear; Research grant / Funding (institution): Navigate/Novartis; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): Lilly. L. Pusztai: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self),
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.010/5577928 by guest on 26 October 2019
(institution): AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Roche; Advisory / Consultancy: Laboratorios Farmaceuticos Rovi; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Novartis; Licensing / Royalties: Cytovation. E.S. Blix: Honoraria (self): Pfizer. B. Gilje: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Astellas Oncology; Research grant / Funding (institution): Cellgene; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Pierre Fabre. E.A. Janssen: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. J. Geisler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Speaker Bureau / Expert testimony: Brystol-Myers-Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer. T. Aas: Honoraria (self): AstraZenaca; Honoraria (self): Roche. S. Knappskog: Honoraria (self), Research grant / Funding (institution): AstraZenaca; Honoraria (self), Research grant / Funding (institution): Pfizer; Licensing / Royalties: Patent EP2389450 A1,Patent WO 2012/010661. H.P. Eikesdal: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZenaca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self): HAI Interaktiv AS; Honoraria (self): Dagens Medisin; Honoraria (self): Brystol-Myers-Squibb; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Abbvie. All other authors have declared no conflicts of interest.
Annals of Oncology