- Email: [email protected]
RIBOB: A study on the efficacy and safety of ribociclib in combination with letrozole in older women (≥70 years) with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior systemic therapy for advanced disease
abstracts
Novartis, Celgene, Eli Lilly, EISAI, Roche; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Novartis, Roche, Pfizer. J. Balmana: Advisory / Consultancy: AstraZeneca, Pfizer. E. L opez-Miranda: Full / Part-time employment: Medica Scientia Innovation Research (MedSIR). J. Corte´s: Advisory / Consultancy: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex; Honoraria (institution): Roche, Novartis, Celgene, Eisai, Pfizer, Samsung; Research grant / Funding (institution): Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). A. Llombart Cussac: Honoraria (institution), Advisory / Consultancy: Roche, GlaxoSmithKline, Novartis, Celgene, Eisai, AstraZeneca; Research grant / Funding (institution): GlaxoSmithKline, Sanofi, Puma Biotechnology; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). All other authors have declared no conflicts of interest.
385TiP
RIBOB: A study on the efficacy and safety of ribociclib in combination with letrozole in older women (70 years) with hormone receptorpositive (HR1) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior systemic therapy for advanced disease
C. Kenis1, N.F. Ponde2, L. Decoster3, E. de Azambuja4, G. Jerusalem5, P. Neven6, L. Dal Lago7, H. Denys8, P. Vuylsteke9, F.P. Duhoux10, H. Wildiers1 1 General Medical Oncology, University Hospitals Leuven - Campus Gasthuisberg, ao Leuven, Belgium, 2Medical Oncology Department, AC Camargo Cancer Center, S~ Paulo, Brazil, 3Department of Medical Oncology, UZ Brussel, Brussels, Belgium, 4 5 Academic Promoting Team, Institute Jules Bordet, Brussels, Belgium, Medical Oncology, Sart-CHU Sart Tilman Liege, Liege, Belgium, 6Vesalius Research Center - VIB, University Hospitals Leuven, KU Leuven, University of Leuven, Leuven, Belgium, 7Medical Oncology Department, Institute Jules Bordet, Brussels, Belgium, 8Medical Oncology Department, UZ Gent, Ghent, Belgium, 9Department of Oncology, CHU-UCL-Namur Clinique Ste Elisabeth, Namur, Belgium, 10Oncology, Cliniques Universitaires St. Luc, Brussels, Belgium Background: Ribociclib in combination with endocrine therapy (ET) is the current standard of care in first-line for HRþ/HER2- aBC. An increasing proportion of patients who are candidates for ribociclib are older (70 years of age). The number of older patients who have participated thus far in ribocicib trials is, however, small, and little data is available on the tolerability of ribociclib in this population, particularly among frail older patients. Previous trials, moreover, do not usually include older patient-specific methods of evaluation (comprehensive geriatric assessment). RIBOB addresses the issue of efficacy and tolerability of ribociclib in older patients, including frail patients and patients with multiple comorbidities as is frequent in clinical practice. Trial design: Ribob is a prospective, open lable, single arm trial which will evaluate the clinical efficacy, overall safety and tolerability of ribociclib in combination with letrozole in older women (70 years) with HRþ/HER2- aBC and no prior hormonal treatment for advanced disease (as per approved indication). Frail patients, patients with comorbidities and patients with altered laboratory tests for whom treatment is deemed adequate and safe by the local investigator are eligible. Exclusion criteria include patients with uncontrolled brain lesions and QTc interval prolongation. A total of 150 patients will be enrolled for treatment with Letrozole (2.5 mg once daily) þ ribociclib 600 mg (day 1 to 21 in a 28 day cycle) until progression, intolerable toxicity or patient/ physician decision to withdraw. Study end-points include PFS, OS, safety and functionality, which will be evaluated through EORTC QLQ-C30 (modified) and EORTC IL15 questionnaires as well comprehensive geriatric assessment at baseline, 3 months and 1 year. Translational research will include the collection of plasma samples which will be obtained to evaluate aging biomarkers and thymidine kinase and their impact on efficacy and toxicity. Recruitment is open since January/2019. Legal entity responsible for the study: UZ Leuven. Funding: Novartis.
v140 | Breast Cancer, Metastatic
Disclosure: N.F. Ponde: Research grant / Funding (self), Travel Grant: Novartis. L. Decoster: Research grant / Funding (self): Boehringer-Ingelheim; Research grant / Funding (self): Roche; Research grant / Funding (self): BMS. E. de Azambuja: Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Research grant / Funding (self): GSK. G. Jerusalem: Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): Amgen; Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Puma; Honoraria (self): Daiichi-Sankyo; Honoraria (self): AZ; Honoraria (self): Lilly; Honoraria (self): Celgene; Research grant / Funding (self): MSD. P. Vuylsteke: Research grant / Funding (self): Roche. H. Wildiers: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy: Celldex; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): PUMA. All other authors have declared no conflicts of interest.
386TiP
RIbociclib plus goserelin with hormonal therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with HR1, HER2– inoperable locally advanced or metastatic breast cancer: RIGHT choice study
N. El Saghir1, S. Malwinder2, H. Azim3, Y. Eralp4, S-A. Im5, Y.S. Yap6, T. Delgar Alfaro7, M. Gao7, Y-S. Lu8 1 Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon, 2 Clinical Oncology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, 3Oncology, Cairo Oncology Center Cairo Hospital-CairoCure, Giza, Egypt, 4Oncology, Istanbul Florence Nightingale Hospital, Istanbul, Turkey, 5Internal Medicine, SNUH-Seoul National University Hospital, Seoul, Republic of Korea, 6Medical Oncology, NCCS - National Cancer Centre Singapore, 7Oncology, Novartis, Basel, Switzerland, 8Oncology, National Taiwan University Hospital, Taipei, Taiwan Background: A high percentage of breast cancer patients in the Asia-Pacific (42%) and Middle East (50%) regions are aged 50 years or younger. Although a high proportion of younger patients with endocrine-responsive metastatic disease are treated initially with cytotoxic chemotherapy (CT) in routine general practice, data from phase III trials have shown higher response rates and longer progression-free survival with endocrine therapy (ET) in combination with CDK4/6 inhibitor versus single agent ET. Due to lack of direct evidence, trials in pre-/perimenopausal advanced breast cancer are thus necessary to assess the efficacy of ET in combination with CDK4/6 inhibitor vs CT in aggressive or high tumor burden setting where CT is clinically indicated. Trial design: The RIGHT Choice study (NCT03839823) is a randomized, open-label, multination phase 2 study with a target enrollment (approximately 55 sites in 13 countries in the Asia-Pacific and Middle East regions) of 222 pre-/perimenopausal women aged 18-59 years who have not received prior systemic ET or CT for advanced disease. Patients must have advanced HRþ, HER2– breast cancer not amenable to curative therapy (ie, symptomatic visceral metastases, rapid progression of disease or impending visceral compromise, or markedly symptomatic nonvisceral disease where combination chemotherapy is clinically indicated). Tumors must be estrogen receptorpositive 10%; and ECOG performance status 2. Exclusion criteria include pregnancy or lactation, and postmenopausal status. Patients will be randomized to receive ribociclib (600 mg, 3 weeks on/1 week off) in combination with letrozole or anastrozole plus goserelin or to investigator’s choice of combination CT (docetaxel þ capecitabine, paclitaxel þ gemcitabine, or capecitabine þ vinorelbine). The primary endpoint is progression-free survival. Secondary endpoints include time to treatment failure, overall response rate, clinical benefit rate, time to response, overall survival, patient global health status, and safety. Healthcare resource utilization will be evaluated as an exploratory endpoint. Clinical trial identification: NCT03839823. Editorial acknowledgement: Medical editorial assistance was provided by Rob Camp, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study: Novartis Pharmaceuticals. Funding: Novartis Pharmaceuticals. Disclosure: S.S. Malwinder: Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: AstraZeneca. H.A. Azim: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Hekma. Y. Eralp: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony, Non-remunerated activity/ies: BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Pfizer; Non-remunerated activity/ies: Nobel; Research grant / Funding (institution): AstraZeneca; Leadership role: Istanbul Breast Cancer Research Group (IMAG). S. Im: Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Roche; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Pfizer. Y.S. Yap: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. T. Delgar Alfaro: Full / Part-
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.080/5577541 by guest on 26 October 2019
(IV/SC at standard dose) until progression or unacceptable toxicity. Main selection criteria: (1) Pre– and post–menopausal women with HER2[þ] ABC; (2) 3 prior regimens of chemotherapy and/or trastuzumab–lapatinib in advanced setting, and at least 1 regimen of chemotherapy including trastuzumab; (3) Pts treated with carboplatin or platinum compounds in the last 12 months are not eligible; (4) Evaluable or measurable disease. Co–Primary objectives: Overall response rate (ORR) and PFS of olaparib plus trastuzumab in the cohort A. In the cohort A (N ¼ 20), we plan a Simon’s two–stage design (7 pts in the 1st stage and 13 pts in the 2nd stage in case of any responder in 1st stage). Final ORR will be promising with 4 responders among 18 evaluable pts (H0: ORR5%; HA: ORR30%). PFS estimation will be based a one–arm log–rank test (H0: PFS3–months; HA: PFS6–months). These give us an 80% power at 0.025 one– sided alpha level. In the cohort B (N ¼ 13) ORR will be promising with 3 responders among 13 pts (p < 0.025; H0: ORR5%). Secondary objectives: Safety–related outcomes, clinical benefit rate, overall survival, and quality of life. Exploratory objectives: Prevalence of gBRCAm and HRD in HER2[þ] ABC, and identification of new potential predictive markers. Clinical trial identification: NCT03931551. First Posted: April 30, 2019. Legal entity responsible for the study: Medica Scientia Innovation Research (MedSIR); Experior. Funding: AstraZeneca Famace´utica Spain S.A. Disclosure: J.A. Garcıa-Saenz: Advisory / Consultancy, Speaker Bureau / Expert testimony:
Annals of Oncology
Novartis, Celgene, Eli Lilly, EISAI, Roche; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Novartis, Roche, Pfizer. J. Balmana: Advisory / Consultancy: AstraZeneca, Pfizer. E. L opez-Miranda: Full / Part-time employment: Medica Scientia Innovation Research (MedSIR). J. Corte´s: Advisory / Consultancy: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex; Honoraria (institution): Roche, Novartis, Celgene, Eisai, Pfizer, Samsung; Research grant / Funding (institution): Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). A. Llombart Cussac: Honoraria (institution), Advisory / Consultancy: Roche, GlaxoSmithKline, Novartis, Celgene, Eisai, AstraZeneca; Research grant / Funding (institution): GlaxoSmithKline, Sanofi, Puma Biotechnology; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). All other authors have declared no conflicts of interest.
385TiP
RIBOB: A study on the efficacy and safety of ribociclib in combination with letrozole in older women (70 years) with hormone receptorpositive (HR1) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior systemic therapy for advanced disease
C. Kenis1, N.F. Ponde2, L. Decoster3, E. de Azambuja4, G. Jerusalem5, P. Neven6, L. Dal Lago7, H. Denys8, P. Vuylsteke9, F.P. Duhoux10, H. Wildiers1 1 General Medical Oncology, University Hospitals Leuven - Campus Gasthuisberg, ao Leuven, Belgium, 2Medical Oncology Department, AC Camargo Cancer Center, S~ Paulo, Brazil, 3Department of Medical Oncology, UZ Brussel, Brussels, Belgium, 4 5 Academic Promoting Team, Institute Jules Bordet, Brussels, Belgium, Medical Oncology, Sart-CHU Sart Tilman Liege, Liege, Belgium, 6Vesalius Research Center - VIB, University Hospitals Leuven, KU Leuven, University of Leuven, Leuven, Belgium, 7Medical Oncology Department, Institute Jules Bordet, Brussels, Belgium, 8Medical Oncology Department, UZ Gent, Ghent, Belgium, 9Department of Oncology, CHU-UCL-Namur Clinique Ste Elisabeth, Namur, Belgium, 10Oncology, Cliniques Universitaires St. Luc, Brussels, Belgium Background: Ribociclib in combination with endocrine therapy (ET) is the current standard of care in first-line for HRþ/HER2- aBC. An increasing proportion of patients who are candidates for ribociclib are older (70 years of age). The number of older patients who have participated thus far in ribocicib trials is, however, small, and little data is available on the tolerability of ribociclib in this population, particularly among frail older patients. Previous trials, moreover, do not usually include older patient-specific methods of evaluation (comprehensive geriatric assessment). RIBOB addresses the issue of efficacy and tolerability of ribociclib in older patients, including frail patients and patients with multiple comorbidities as is frequent in clinical practice. Trial design: Ribob is a prospective, open lable, single arm trial which will evaluate the clinical efficacy, overall safety and tolerability of ribociclib in combination with letrozole in older women (70 years) with HRþ/HER2- aBC and no prior hormonal treatment for advanced disease (as per approved indication). Frail patients, patients with comorbidities and patients with altered laboratory tests for whom treatment is deemed adequate and safe by the local investigator are eligible. Exclusion criteria include patients with uncontrolled brain lesions and QTc interval prolongation. A total of 150 patients will be enrolled for treatment with Letrozole (2.5 mg once daily) þ ribociclib 600 mg (day 1 to 21 in a 28 day cycle) until progression, intolerable toxicity or patient/ physician decision to withdraw. Study end-points include PFS, OS, safety and functionality, which will be evaluated through EORTC QLQ-C30 (modified) and EORTC IL15 questionnaires as well comprehensive geriatric assessment at baseline, 3 months and 1 year. Translational research will include the collection of plasma samples which will be obtained to evaluate aging biomarkers and thymidine kinase and their impact on efficacy and toxicity. Recruitment is open since January/2019. Legal entity responsible for the study: UZ Leuven. Funding: Novartis.
v140 | Breast Cancer, Metastatic
Disclosure: N.F. Ponde: Research grant / Funding (self), Travel Grant: Novartis. L. Decoster: Research grant / Funding (self): Boehringer-Ingelheim; Research grant / Funding (self): Roche; Research grant / Funding (self): BMS. E. de Azambuja: Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Research grant / Funding (self): GSK. G. Jerusalem: Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): Amgen; Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Puma; Honoraria (self): Daiichi-Sankyo; Honoraria (self): AZ; Honoraria (self): Lilly; Honoraria (self): Celgene; Research grant / Funding (self): MSD. P. Vuylsteke: Research grant / Funding (self): Roche. H. Wildiers: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy: Celldex; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): PUMA. All other authors have declared no conflicts of interest.
386TiP
RIbociclib plus goserelin with hormonal therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with HR1, HER2– inoperable locally advanced or metastatic breast cancer: RIGHT choice study
N. El Saghir1, S. Malwinder2, H. Azim3, Y. Eralp4, S-A. Im5, Y.S. Yap6, T. Delgar Alfaro7, M. Gao7, Y-S. Lu8 1 Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon, 2 Clinical Oncology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, 3Oncology, Cairo Oncology Center Cairo Hospital-CairoCure, Giza, Egypt, 4Oncology, Istanbul Florence Nightingale Hospital, Istanbul, Turkey, 5Internal Medicine, SNUH-Seoul National University Hospital, Seoul, Republic of Korea, 6Medical Oncology, NCCS - National Cancer Centre Singapore, 7Oncology, Novartis, Basel, Switzerland, 8Oncology, National Taiwan University Hospital, Taipei, Taiwan Background: A high percentage of breast cancer patients in the Asia-Pacific (42%) and Middle East (50%) regions are aged 50 years or younger. Although a high proportion of younger patients with endocrine-responsive metastatic disease are treated initially with cytotoxic chemotherapy (CT) in routine general practice, data from phase III trials have shown higher response rates and longer progression-free survival with endocrine therapy (ET) in combination with CDK4/6 inhibitor versus single agent ET. Due to lack of direct evidence, trials in pre-/perimenopausal advanced breast cancer are thus necessary to assess the efficacy of ET in combination with CDK4/6 inhibitor vs CT in aggressive or high tumor burden setting where CT is clinically indicated. Trial design: The RIGHT Choice study (NCT03839823) is a randomized, open-label, multination phase 2 study with a target enrollment (approximately 55 sites in 13 countries in the Asia-Pacific and Middle East regions) of 222 pre-/perimenopausal women aged 18-59 years who have not received prior systemic ET or CT for advanced disease. Patients must have advanced HRþ, HER2– breast cancer not amenable to curative therapy (ie, symptomatic visceral metastases, rapid progression of disease or impending visceral compromise, or markedly symptomatic nonvisceral disease where combination chemotherapy is clinically indicated). Tumors must be estrogen receptorpositive 10%; and ECOG performance status 2. Exclusion criteria include pregnancy or lactation, and postmenopausal status. Patients will be randomized to receive ribociclib (600 mg, 3 weeks on/1 week off) in combination with letrozole or anastrozole plus goserelin or to investigator’s choice of combination CT (docetaxel þ capecitabine, paclitaxel þ gemcitabine, or capecitabine þ vinorelbine). The primary endpoint is progression-free survival. Secondary endpoints include time to treatment failure, overall response rate, clinical benefit rate, time to response, overall survival, patient global health status, and safety. Healthcare resource utilization will be evaluated as an exploratory endpoint. Clinical trial identification: NCT03839823. Editorial acknowledgement: Medical editorial assistance was provided by Rob Camp, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study: Novartis Pharmaceuticals. Funding: Novartis Pharmaceuticals. Disclosure: S.S. Malwinder: Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: AstraZeneca. H.A. Azim: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Hekma. Y. Eralp: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony, Non-remunerated activity/ies: BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Pfizer; Non-remunerated activity/ies: Nobel; Research grant / Funding (institution): AstraZeneca; Leadership role: Istanbul Breast Cancer Research Group (IMAG). S. Im: Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Roche; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Pfizer. Y.S. Yap: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. T. Delgar Alfaro: Full / Part-
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz242.080/5577541 by guest on 26 October 2019
(IV/SC at standard dose) until progression or unacceptable toxicity. Main selection criteria: (1) Pre– and post–menopausal women with HER2[þ] ABC; (2) 3 prior regimens of chemotherapy and/or trastuzumab–lapatinib in advanced setting, and at least 1 regimen of chemotherapy including trastuzumab; (3) Pts treated with carboplatin or platinum compounds in the last 12 months are not eligible; (4) Evaluable or measurable disease. Co–Primary objectives: Overall response rate (ORR) and PFS of olaparib plus trastuzumab in the cohort A. In the cohort A (N ¼ 20), we plan a Simon’s two–stage design (7 pts in the 1st stage and 13 pts in the 2nd stage in case of any responder in 1st stage). Final ORR will be promising with 4 responders among 18 evaluable pts (H0: ORR5%; HA: ORR30%). PFS estimation will be based a one–arm log–rank test (H0: PFS3–months; HA: PFS6–months). These give us an 80% power at 0.025 one– sided alpha level. In the cohort B (N ¼ 13) ORR will be promising with 3 responders among 13 pts (p < 0.025; H0: ORR5%). Secondary objectives: Safety–related outcomes, clinical benefit rate, overall survival, and quality of life. Exploratory objectives: Prevalence of gBRCAm and HRD in HER2[þ] ABC, and identification of new potential predictive markers. Clinical trial identification: NCT03931551. First Posted: April 30, 2019. Legal entity responsible for the study: Medica Scientia Innovation Research (MedSIR); Experior. Funding: AstraZeneca Famace´utica Spain S.A. Disclosure: J.A. Garcıa-Saenz: Advisory / Consultancy, Speaker Bureau / Expert testimony:
Annals of Oncology