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1. Efficacy, Safety, Pharmacokinetics, and Immunogenicity of DRL-Trastuzumab Versus Herceptin in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: A Randomized Controlled Trial

Author

Naveen Reddy, Pramod Reddy, Ankit Ranpura, Narendra Maharaj, Rajendersingh Arora, Gopichand Mamillapalli, Aditya Shirish Adhav, Ashok Kumar Diwan, Alexey Manikhas, and Dmitriy Krasnozhon

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PURPOSEDr Reddy's Laboratories Trastuzumab (DRL_TZ) is a biosimilar to Herceptin under development. The present study was conducted to evaluate efficacy, safety, pharmacokinetics (PKs), and immunogenicity of DRL_TZ in comparison with the reference medicinal product (RMP) along with concomitant weekly paclitaxel in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC).METHODSThis was a randomized, double-blind study in female patients with HER2-positive MBC, randomly assigned in a 1:1 ratio to receive either DRL_TZ or the RMP, that is, an innovator product sourced from the European region, along with additional chemotherapy, as first-line treatment for up to 24 weeks. The primary end point was the best overall response rate (ORR) as per RECIST 1.1 criteria. Progression-free survival rate at 6 months (PFS6), safety, immunogenicity, and PK parameters were assessed as secondary end points.RESULTSA total of 164 patients were randomly assigned to receive either DRL_TZ or the RMP. Best ORR in the per-protocol population was comparable, 91.9% (93.3% CI, 83.2 to 96.3) versus 82.1% (93.3% CI, 72.0 to 89.1) in DRL_TZ and RMP arms, respectively; the difference between the arms was 9.8% with a 93.3% CI of –1.3 to 20.8. The PFS6 rate, safety, PK profile, and antidrug antibody incidence were comparable. An additional 44 patients were recruited in the postrandomization phase, in an open-label manner, and started on DRL_TZ to generate more data on efficacy, safety, and immunogenicity. The additional data with DRL_TZ, when pooled, were similar to the RMP data.CONCLUSIONDRL_TZ was found to have similar efficacy and comparable safety, PK, and immunogenicity profiles as the RMP.

Published
2024
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2. Safety and efficacy of adjuvant subcutaneous trastuzumab in human epidermal growth factor receptor 2-positive early breast cancer: Final results of the SafeHER study

Author

Joseph Gligorov, Xavier Pivot, Beyhan Ataseven, Michelino De Laurentiis, Kyung Hae Jung, Alexey Manikhas, Hamdy Abdel Azim, Kushagra Gupta, Ari Alexandrou, Luis Herraez-Baranda, Nadia Tosti, and Eleonora Restuccia

Subjects
Breast neoplasms, Disease-free survival, Follow-up studies, Receptor ErbB2, Safety, Trastuzumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Aim: To report the final results of the 5-year follow-up of the non-randomized SafeHER Phase III study (NCT01566721) describing the safety, tolerability, and efficacy of subcutaneous (SC) trastuzumab alone and in combination with concurrent or sequential chemotherapy. Methods: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) with no prior anti-HER2 therapy were included. SC trastuzumab was administered every 3 weeks for 18 cycles as adjuvant therapy with or without chemotherapy (concurrent or sequential). The primary objective was overall safety and tolerability of SC trastuzumab; efficacy was a secondary objective. Results: No new safety signals were observed during the final evaluation. The majority of adverse events (AEs) were grade 1 or 2 across the chemotherapy subgroups. Treatment discontinuation due to AEs was 5.1% for the intent-to-treat (ITT) population and similar for all chemotherapy subgroups. The overall disease-free survival (DFS) 5-year event-free rate in the ITT population (n = 2573) was 86.6% (95% CI, 85.2%–87.9%) with a median follow-up of 72 months. Based on chemotherapy timing, the no (n = 235), concurrent (n = 1533), and sequential (n = 805) chemotherapy subgroups had DFS 5-year event-free rates (95% CI) of 88.5% (83.4%–92.2%), 88.4% (86.6%–89.9%), and 82.6 (79.7%–85.2%), respectively. Conclusions: The 5-year follow-up analysis of the SafeHER trial demonstrating that SC trastuzumab has an acceptable safety profile, including cardiac toxicity, and efficacy for the treatment of HER2-positive EBC with and without chemotherapy, corresponding with historical data with trastuzumab.

Published
2022
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3. Correlation between week 24 trastuzumab-dkst response and week 48 progression-free survival: the HERITAGE trial

Author

Hope S. Rugo, Eduardo J. Pennella, Unmesh Gopalakrishnan, Miguel Hernandez-Bronchud, Jay Herson, Hans Friedrich Koch, Subramanian Loganathan, Sarika Deodhar, Ashwani Marwah, Alexey Manikhas, Igor Bondarenko, Joseph D. Parra, Maria Luisa T. Abesamis-Tiambeng, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Sirshendu Roy, Eduardo Patricio Yanez Ruiz, Abhijit Barve, and Cornelius F. Waller

Subjects
Biosimilar, Combination therapy, Efficacy, Metastatic breast cancer, Monotherapy, Safety, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity. Methods: HERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy. Results: Of 500 randomized patients, 342 entered the monotherapy phase; 214 patients received ≥48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim overall survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was highly correlated with week 48 PFS (rb = 0.75). Cumulative treatment-emergent adverse events (TEAEs) and serious AEs were similar in both groups, with few grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks. Conclusion: The correlation between ORR and PFS supports the design of first-line metastatic trials assessing biosimilar trastuzumab. Overall, trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy, including ORR and PFS, in combination with a taxane followed by monotherapy.

Published
2021
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4. Correlation between week 24 trastuzumab-dkst response and week 48 progression-free survival: the HERITAGE trial

Author

Cornelius F. Waller, Maria Luisa T. Abesamis-Tiambeng, Charuwan Akewanlop, Eduardo Yanez Ruiz, Ihor Vynnychenko, Unmesh Gopalakrishnan, Abhijit Barve, Jay Herson, Ashwani Marwah, Virote Sriuranpong, Sirshendu Roy, Hope S. Rugo, Alexey Manikhas, Miguel Hernandez-Bronchud, Subramanian Loganathan, Hans Friedrich Koch, Joseph D. Parra, Sarika Deodhar, Igor Bondarenko, and Eduardo J. Pennella

Subjects
Oncology, medicine.medical_specialty, Combination therapy, Efficacy, Receptor, ErbB-2, Phases of clinical research, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Trastuzumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Progression-free survival, Adverse effect, skin and connective tissue diseases, neoplasms, RC254-282, Taxane, business.industry, Biosimilar, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, General Medicine, medicine.disease, Metastatic breast cancer, Monotherapy, Tolerability, 030220 oncology & carcinogenesis, Female, Original Article, Surgery, Safety, business, medicine.drug
Abstract

Background Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity. Methods HERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy. Results Of 500 randomized patients, 342 entered the monotherapy phase; 214 patients received ≥48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim overall survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was highly correlated with week 48 PFS (rb = 0.75). Cumulative treatment-emergent adverse events (TEAEs) and serious AEs were similar in both groups, with few grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks. Conclusion The correlation between ORR and PFS supports the design of first-line metastatic trials assessing biosimilar trastuzumab. Overall, trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy, including ORR and PFS, in combination with a taxane followed by monotherapy., Highlights • Trastuzumab-dkst is a biosimilar of trastuzumab. • Trastuzumab-dkst and trastuzumab had similar PFS, ORR, and OS at week 48. • Results support therapeutic equivalence between trastuzumab-dkst and trastuzumab. • Week 24 ORR was highly correlated with week 48 PFS. • ORR and PFS correlation supports ORR as a valid endpoint in clinical trials for MBC.

Published
2021

5. Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial

Author

Giorgi Dzagnidze, Justin Stebbing, Alexey Manikhas, Alexandru Eniu, Rubi K. Li, V. Baryash, Edvard Zhavrid, Joanna Pikiel, Vladimir Moiseyenko, Dmytro Boliukh, Yauheni Valerievich Baranau, Sang Joon Lee, Sunghyun Kim, Beatrice Tiangco, National Institute for Health Research, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, MULTICENTER, THERAPY, Ventricular Function, Left, 0302 clinical medicine, Trastuzumab, CYCLOPHOSPHAMIDE, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, skin and connective tissue diseases, Neoadjuvant therapy, ADJUVANT TRASTUZUMAB, DOCETAXEL, education.field_of_study, OUTCOMES, Biosimilar, HER2-positive early breast cancer, Hazard ratio, ASSOCIATION, OPEN-LABEL, Clinical Trial, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, SURVIVAL, Female, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Population, Breast Neoplasms, Adjuvant therapy, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, education, CT-P6, Biosimilar Pharmaceuticals, Chemotherapy, Science & Technology, business.industry, 1103 Clinical Sciences, Stroke Volume, medicine.disease, 030104 developmental biology, business
Abstract

Purpose Equivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years’ follow-up. Methods Following neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up. Results Most patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78–1.93) for DFS, 1.31 (0.86–2.01) for PFS, and 1.10 (0.57–2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups. Conclusion The similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab. ClinicalTrials.gov: NCT02162667 (registered June 13, 2014)

Published
2021

6. 5-year follow-up of the safety, tolerability and efficacy of subcutaneous trastuzumab for the adjuvant treatment of HER2-positive early breast cancer. Results from the SafeHER Phase III trial

Author

Alexey Manikhas, B. Ataseven, Joseph Gligorov, Kyung Hwa Jung, L. Herraez-Baranda, Antonio Llombart, Eleonora Restuccia, Xavier Pivot, A. Alexandrou, K. Gupta, M. De Laurentiis, N. Tosti, and Hamdy A. Azim

Subjects
Oncology, medicine.medical_specialty, 5 year follow up, business.industry, medicine.medical_treatment, Safety tolerability, General Medicine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Trastuzumab, Internal medicine, medicine, Surgery, business, Adjuvant, medicine.drug, Early breast cancer
Published
2021

7. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial

Author

Justin Stebbing, V. Baryash, Alexandru Eniu, Joanna Pikiel, S. Young Lee, Francisco J. Esteva, S. Yu, Yauheni Valerievich Baranau, R. K. Li, Sang Joon Lee, Daniil Stroyakovskiy, Andriy Rusyn, Dmytro Boliukh, B. Tiangco, Vladimir Moiseyenko, Giorgi Dzagnidze, Edvard Zhavrid, and Alexey Manikhas

Subjects
0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, Toxicology, NEOADJUVANT CHEMOTHERAPY, 0302 clinical medicine, Antineoplastic Agents, Immunological, Breast cancer, Trastuzumab, Pharmacology (medical), Pharmacology & Pharmacy, PATHOLOGICAL COMPLETE RESPONSE, Stage (cooking), skin and connective tissue diseases, Complete response, Adjuvant, Early breast cancer, ADJUVANT TRASTUZUMAB, Biosimilar, Middle Aged, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Original Article, Drug Monitoring, 1115 Pharmacology and Pharmaceutical Sciences, Life Sciences & Biomedicine, medicine.drug, HER2 positive, medicine.medical_specialty, Breast Neoplasms, 03 medical and health sciences, Internal medicine, medicine, Humans, Oncology & Carcinogenesis, Adverse effect, CT-P6, Biosimilar Pharmaceuticals, neoplasms, Neoplasm Staging, Pharmacology, Heart Failure, Science & Technology, business.industry, medicine.disease, CONTROLLED SUPERIORITY TRIAL, 030104 developmental biology, Heart failure, business, FOLLOW-UP
Abstract

Purpose Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures. Methods Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year. Results In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs. Conclusion Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability. Electronic supplementary material The online version of this article (10.1007/s00280-019-03920-4) contains supplementary material, which is available to authorized users.

Published
2019

8. BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

Author

Marina Matrosova, Kritiya Butthongkomvong, Steen Lindkær-Jensen, Vichien Srimuninnimit, Ekaterina Trishkina, Alexey Manikhas, Elena Poddubuskaya, and Stig Larsen

Subjects
medicine.medical_specialty, Hematology, improved Quality of Life, business.industry, Cancer, Common Terminology Criteria for Adverse Events, Targets and Therapy [Breast Cancer], medicine.disease, Placebo, Metastatic breast cancer, safe, Breast cancer, few transient adverse effects, Oncology, Tolerability, Quality of life, Internal medicine, medicine, tumor growth reduction, business, Biomedical engineering, Original Research
Abstract

Stig Larsen,1 Kritiya Butthongkomvong,2 Alexey Manikhas,3 Ekaterina Trishkina,4 Elena Poddubuskaya,5 Marina Matrosova,6 Vichien Srimuninnimit,7 Steen Lindkær-Jensen81Department of Controlled Clinical Trials and Biostatistics, Centre for Epidemiology and Biostatistics, University of Life Science, Oslo, Norway; 2Udonthani Cancer Hospital, Udonthani, Thailand; 3Department of Oncology, City Clinical Oncology, Dispensary, St Petersburg, Russia; 4Department of Oncology, Leningrad Regional Oncology Centre, St Petersburg, Russia; 5Department of Oncology, Unit of Russian Academy of Medical Science, Moscow, Russia; 6Department of Oncology, N Novgorod Regional Oncology Dispensary, Novgorod, Russia; 7Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 8Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UKAbstract: The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer.Material and methods: A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI), European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer–specific BR23) data were recorded at screening and after every 16 days of treatment. Computed tomography was performed at screening and every 32 days.Results: The sum of target lesions increased 2.4% in the BP-C1 group and 14.3% in the placebo group. Only the increase in the placebo group was significant (P=0.013). The difference between the groups was significant in favor of BP-C1 (P=0.04). There was a significant difference (P=0.026) in favor of BP-C1 regarding Response Evaluation Criteria In Solid Tumors (RECIST) classification. The sum of lesions increased slightly in the patients receiving 64 days of continuous BP-C1 treatment, of whom 68.4% were classified as responders. The sum CTC-NCI toxicity score increased nonsignificantly in the BP-C1 group but significantly in the placebo group (P=0.05). The difference in increase between groups did not meet the level of significance (P=0.12). The sum toxicity score was reduced in the patients receiving 64 days of BP-C1 from 9.2 at screening to 8.9 at Day 48, but it increased again to 10.1 by Day 64 and 10.6 during the 28-day follow-up. "Breast cancer-related pain and discomfort" and "Breast cancer treatment problem last week" were significantly reduced (P=0.02) in the BP-C1 group but increased slightly in the placebo group; between-group differences were significant in favor of BP-C1 (P=0.05). "Breast cancer related pain and discomfort", "Breast cancer treatment problem last week," and "Physical activity problem" were significantly reduced during the 64 days of BP-C1 treatment (P≤0.05).Conclusion: For patients suffering from stage IV metastatic breast cancer, treatment with BP-C1 reduces cancer growth, is well tolerated, improves quality of life, and produces few adverse events, which were mainly mild and manageable.Keywords: tumor growth reduction, improved Quality of Life, safe, few transient adverse effectsCorrigendumfor this paper has been published

Published
2014

9. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author

Jose Chacon, Katja Ziegler-Löhr, Kamran Rashid, Stanley Madretsma, Hortense Laharie Mineur, Soo Hyeon Lee, Bohuslav Melichar, Jasna Pesic, Julia Hall, Jörg Schilling, Paola Morales Espinosa, Wendy Taylor, Francesco Cognetti, Doris Augustin, Ines Sandri, Laura Murillo Jaso, Alejandro Juarez Ramiro, Nora Artagaveytia, Rocio Reategui, Nataliia Voitko, Teresa Gamucci, Lisa H Barraclough, Jérôme Alexandre, Mohammed Butt, Frank Priou, A.J. van de Wouw, Cristina Marinela Oprean, Isabel Alonso, Suzana Vasovic, Fernando Roque, Marc Thill, Viktoria Dvornichenko, K. Bouzid, Idris Yucel, Andrea Stefek, Jose Manuel Lopez Vega, Daniil Stroyakovskiy, R. Chiara Forcignanò, Mohammed Harb, Andrzej Mruk, Jana Prausová, Lydia Dreosti, Prabir Chakraborti, Armando Santoro, Lee Wei Ching, Anna Tuczek, Jane Beith, Larisa Ciule, Hakan Bozcuk, Antonino Musolino, Hartmut Kristeleit, Clare Crowley, T.C. Kok, Dhurata Koroveshi, Natasha Mithal, Laura Garcia Sanchis, Stephan Henschen, Carmen Cañabate Arias, A. Contu, Antoaneta Tomova, Alper Sevinc, Helga Droogendijk, Gustavo Fernando Ismael, Konstantinos Papazisis, Laurent Gasnault, Sandra Bakker, Judit Kocsis, Bernd Christensen, Stephen Kelly, Rosana Jarcau, Christian Jackisch, George Fountzilas, Cyril Foa, Annebeth W. Haringhuizen, Silvia Neciosup, Juan Matos Santos, Finlander Rosales Osegueda, Robinson Rodriguez, Marcus Schmidt, Bart de Valk, Kathryn Wright, A.S. Dhadda, Elizabeth Sherwin, Sabino De Placido, Luigi Cavanna, Joelle Egreteau, Shazza Rehman, Giacomo Allegrini, Doerte Luedders, Poovandren Govender, Hugues Barletta, Iztok Takač, Yuraima Garcia, Michael Green, Geneviève Jolimoy, Marcela Urrego, Chanyoot Bandidwattanawong, Vito Lorusso, Annette van der Velden, Rene Muñoz, Djumhana Atmakusuma, Christos Papandreou, Craig Macmillan, Hassan Errihani, Iris Schrader, Isabelle Desmoulins, Jean-Marc Ferrero, Mohamed Idris, B. Ataseven, Andre Farrokh, Isabelle Moullet, Iain R. Macpherson, N. Al-Sakaff, Stephen Chia, Blanca Hernando Fernandez De Aranguiz, Lorena Lion, Alexandros Ardavanis, Ani Zlatareva-Petrova, Ernesto Pablo Korbenfeld, Hugo Castro, Mirta Garcia, Heike Passmann-Kegel, Lionel Uwer, Gary Richardson, Marion Paul, Georgia Demetriou, Andreas Köhler, V. Kovcin, Eliot Sims, Gerasimos Aravantinos, Adriana Dominguez, Daniel Rauch, Greta Beyer, Laurence J. C. van Warmerdam, Roberto Bordonaro, Raymond Ng, David Coeffic, Rostislav Vyzula, Bernard Leduc, Jozef Mardiak, Andrea Pigi, Ingo Runnebaum, Jose Angel Garcia Saenz, Areewan Somwangprasert, Cristina Llorca Ferrandiz, Coskun Hasan Senol, Martin Griesshammer, Friedrich Overkamp, Suzanne Nguyen, Maria Turdean, Udaiveer Panwar, Zsuzsanna Nagy, Francesco Giotta, Andreas Schneeweiss, Teresa Ramon y Cajal Asensio, Jae Hong Seo, Joohyuk Sohn, Jean-Philippe Jacquin, Daniela Grecea, Jasmina Nedovic, Arrate Plazaola Alcibar, Tadeusz Pienkowski, Jetske M. Meerum Terwogt, Elmar Stickeler, Hazem I. Assi, Vadim Shirinkin, Grzegorz Slomian, Etela Mišurová, Roberto Hegg, K. Friedrichs, Corinne Dagada, Jean-François Berdah, Fulden Yumuk, Alexandru Eniu, Amit Chakrabarti, Mathias Fehr, Christoph Salat, Dan Lungulescu, Heinrik Martin Strebel, Antonio Llombart Cussac, Rémy Largillier, Stefan Curescu, Albert von der Assen, Emmanuel Guardiola, Andras Csejtei, Tamas Hickish, Krzysztof Krzemieniecki, Yaroslav Shparyk, Ramon Perez Carrion, Michela Donadio, Purificacion Martinez del Prado, Sandra Franco, J.J. Braun, Michael Friedlander, Suhail Anwar, Thierry Petit, Sarah Smith, Rafael Gutierrez Pilarte, Laia Garrigos Cubells, Frans L. G. Erdkamp, Jedzada Maneechavakajorn, Mastura Yusof, Jocelyn Adams, Diana Cascallar, Luis Antonio Fernandez Morales, Max S. Mano, Simon Waters, Carlos Beato, Philippe Martin, Martin Hogg, Isabelle Sillet Bach, Monica Casalnuovo, Klara Mezei, Alexey Manikhas, Margarida Damasceno, Sergey Emelyanov, Gabriella Mariani, Kecman Gordana, Gianfilippo Bertelli, Ignacio Pelaez Fernandez, Damir Vrbanec, Maria Wagnerova, Johannes Petrus Jordaan, Marina Cazzaniga, Mustafa Deryal, Ruth Davis, Abdurrahman Isikdogan, Sanjay Raj, José Juan Illarramendi Mañas, Vinod Ganju, Maria Dolores Torregrosa Maicas, Glenda Ramos, Nugroho Prayogo, H. Orfeuvre, Filipovic S, Joke Tio, Andrew Redfern, M. Shing, Eduardo Yanez, Khalil Zaman, Jin-Seok Ahn, Dino Amadori, Bahriye Aktas, Miriam O'Connor, Uta Ringsdorf, Christophe Desauw, J. Gligorov, Jorge Corona, Michele De Laurentiis, Arthur Wischnik, Paolo Pedrazzoli, Katalin Boér, Caroline Archer, Anne Kendall, Ori Freedman, Maya Tsakova, Dana Lucia Stanculeanu, Kevin Patterson, Cathy Kelly, Nellie Lay Chin Cheah, X. Artignan, Anil A. Joy, Steffi Busch, Monica Nave, Bryan Hennessy, Lorenzo Livi, X. Pivot, R.J.B. Blaisse, Adolfo Murias Rosales, Juan Carlos Alcedo, Dalila Marcano, Emmanuel Beguier, Andreas Müller, László Csaba Mangel, Christina Schlatter, Fernando Gaion, Tjoung-Won Park-Simon, Sebastian Wojcinski, Ute Bückner, Florinel Badulescu, Cynthia Mayte Villarreal Garza, Rozenn Allerton, Mikhail Lichinitser, Damir Gugić, Manuela Rabaglio, Jens Kisro, Iris Scheffen, Vincent Phua, Marc A. Bollet, Giampaolo Biti, M. Verrill, Adrien Melis, Andrew M Wardley, Ali Arican, Hamdy A. Azim, Lelia-Eveline Bauer, Tsai-Wang Chang, Nik Hauser, René Lazaro González Mendoza, Dominique Jaubert, Samreen Ahmed, Mazhar Shah, János Szántó, Kunibert Latos, Xavier Pivot, Helen Gogas, Elona Juozaityte, Luca Moscetti, Helene Simon, Giacomo Carterni, Dan-Corneliu Jinga, Olivia Pagani, Elena Rota Caremoli, Esther Arbona, Cornelia Liedtke, Stylianos Kakolyris, Abdulla Alhasso, Omalkhair Abulkhair, Jose Ponce Lorenzo, Julian Singer, Tony Branson, Claudia Hänle, Ingvild Mjaaland, Chiun-Sheng Huang, Heri Fadjari, Jonathan Joffe, Laetitia Stefani, Dieter Lampe, Franck Burki, S. Lauer, Sabine Schmatloch, Gracieux Fernando, Dina Sakaeva, Christina Balser, Michael Martin, Nora Bittner, Andrea Heider, Antonio Frassoldati, Serafin Morales Murillo, Hakan Akbulut, Saad Tahir, Tilmann Lantzsch, Christine Brezden-Masley, Vanessa Helena, Tran Van Thuan, F.E. de Jongh, Roger K.C. Ngan, Elke Faust, Hugues Bourgeois, Flora Li Tze Chong, Nehal Masood, Keun Seok Lee, J. Bishop, Mathias Warm, Dimitris Mavroudis, Petrosian Veersamy, Judith Fraser, Andres Garcia-Palomo Perez, Heiko Graf, Vanesa Quiroga Garcia, Jyh-Cherng Yu, Maria Jose Villanueva Silva, Elke Simon, Diana Aleman, Kazim Uygun, Cosima Brucker, Michael Weigel, Volkmar Müller, Djohan Kurnianda, Duncan Wheatley, Amr Abdel Aziz, Benno Lex, Laura G. Estévez, Darren Teoh, María Isabel León, Noemia Afonso, Frances Yuille, Amelia Tienghi, Gernot Seipelt, Jose Alberto Nogueira, Dumitru Filip, Zafar Malik, Fatima Cardoso, Giorgio Cruciani, Winnie Yeo, Luis Vera, Santiago Gonzalez Santiago, Richard North, M.W. Dercksen, Zsolt Horváth, Noelia Martinez Jañez, Marta Mion, Marcela Ferrari, Natalia Valdiviezo, Oana Zveltlana Cojocarasu, Alessandra Morelle, Medy Tsalic, Sonia Pernas Simon, Christoph Maintz, Daniele Farci, Alvaro Edson Lessa, Jeremy Monge, Joseph Gligorov, Anthony Neal, Norberto Batista Lopez, Piotr Tomczak, Yesim Eralp, Kasan Seetalarom, Thitiya (Sirisinha) Dejthevaporn, Jamal Zekri, Steven John Proctor, Saira Nasim, Muireann Kelleher, Eftal Yucel, Quirine Clementine van Rossum-Schornagel, Linda Coate, Paolo Marchetti, Theresa Howe, Carlos Alberto Hernandez, Roberto Torres, Konstanta Timcheva, Evaristo Maiello, Anita Prechtl, Jamil Asselah, Branislav Bystricky, Kate Scatchard, Zeba Aziz, Jaroslava Leskova, Sherko Kuemmel, Paolo Bidoli, Richard Ashford, Piotr Sawrycki, Claude Bressac, Alberto Bottini, Pilar Lopez Alvarez, Nadine Dohollou, Alejandro Andres Acevedo Gaete, M. De Laurentiis, T.J. Smilde, Andrew Proctor, Catherine Prady, Michele Aieta, Jan Henry Svensson, Reda Garidi, Erik Wist, Antonia Perello Martorell, Mohammed Jaloudi, Graeme Lumsden, Eva-Maria Grischke, Ali Youssef, Annemieke van der Padt, Kadri Altundag, Christina Bechtner, Mireille Mousseau, Heba El Zawahry, Maartje Los, Alvydas Česas, Alfredo Falcone, Salima Hamizi, Franchette W P J van den Berkmortel, Cesar Estuardo Hernandez-Monroy, K.H. Jung, Swati Kulkarni, R.K. Agrawal, Hwei Chung Wang, Hany Eldeeb, Fredrika Killander, Jose Luis Alonso Romero, Antonio Pazzola, Daan ten Bokkel Huinink, Mario Campone, Beena C.R. Devi, Florence Dalenc, Pedro Jimenez Gallego, Mawin Vongsaisuwon, Timur Ceric, Chantal Bernard Marty, R. A. Popescu, J. van den Bosch, Luis Matamala, Sylvia Ruth, Maria Litwiniuk, Maria Lomas Garrido, Mark Churn, Christian Kersten, Francesco Del Piano, Eddie Herman Tanggo, Antonio Fernandez Aramburo, Kyung Hae Jung, Christos Papadimitriou, Hamdy Abdel Azeem, Patricia Bastick, Tobias Hesse, Maree Colosimo, Lucia Gonzalez Cortijo, Mark Verrill, Gligorov, J, Ataseven, B, Verrill, M, De Laurentiis, M, Jung, K. H, Azim, H. A, Al-sakaff, N, Lauer, S, Shing, M, Pivot, X., de Laurentiis, M, Jung, K, Azim, H, Al-Sakaff, N, Pivot, X, Koroveshi, D, Bouzid, K, Casalnuovo, M, Cascallar, D, Korbenfeld, E, Bastick, P, Beith, J, Colosimo, M, Friedlander, M, Ganju, V, Green, M, Patterson, K, Redfern, A, Richardson, G, Ceric, T, Gordana, K, Beato, C, Ferrari, M, Hegg, R, Helena, V, Ismael, G, Lessa, A, Mano, M, Morelle, A, Nogueira, J, Timcheva, K, Tomova, A, Tsakova, M, Zlatareva-Petrova, A, Asselah, J, Assi, H, Brezden-Masley, C, Chia, S, Freedman, O, Harb, M, Joy, A, Kulkarni, S, Prady, C, Gaete, A, Matamala, L, Torres, R, Yanez, E, Franco, S, Urrego, M, Gugic, D, Vrbanec, D, Melichar, B, Prausova, J, Vyzula, R, Pilarte, R, Leon, M, Munoz, R, Ramos, G, Azeem, H, Aziz, A, El Zawahry, H, Osegueda, F, Alexandre, J, Artignan, X, Barletta, H, Beguier, E, Berdah, J, Marty, C, Bollet, M, Bourgeois, H, Bressac, C, Burki, F, Campone, M, Coeffic, D, Cojocarasu, O, Dagada, C, Dalenc, F, Del Piano, F, Desauw, C, Desmoulins, I, Dohollou, N, Egreteau, J, Ferrero, J, Foa, C, Garidi, R, Gasnault, L, Guardiola, E, Hamizi, S, Jarcau, R, Jacquin, J, Jaubert, D, Jolimoy, G, Mineur, H, Largillier, R, Leduc, B, Martin, P, Melis, A, Monge, J, Moullet, I, Mousseau, M, Nguyen, S, Orfeuvre, H, Petit, T, Priou, F, Bach, I, Simon, H, Stefani, L, Uwer, L, Youssef, A, Aktas, B, von der Assen, A, Augustin, D, Balser, C, Bauer, L, Bechtner, C, Beyer, G, Brucker, C, Buckner, U, Busch, S, Christensen, B, Deryal, M, Farrokh, A, Faust, E, Friedrichs, K, Graf, H, Griesshammer, M, Grischke, E, Hanle, C, Heider, A, Henschen, S, Hesse, T, Jackisch, C, Kisro, J, Kohler, A, Kuemmel, S, Lampe, D, Lantzsch, T, Latos, K, Lex, B, Liedtke, C, Luedders, D, Maintz, C, Muller, V, Overkamp, F, Park-Simon, T, Paul, M, Prechtl, A, Ringsdorf, U, Runnebaum, I, Ruth, S, Salat, C, Scheffen, I, Schilling, J, Schmatloch, S, Schmidt, M, Schneeweiss, A, Schrader, I, Seipelt, G, Simon, E, Stefek, A, Stickeler, E, Thill, M, Tio, J, Tuczek, A, Warm, M, Weigel, M, Wischnik, A, Wojcinski, S, Ziegler-Lohr, K, Aravantinos, G, Ardavanis, A, Fountzilas, G, Gogas, H, Kakolyris, S, Mavroudis, D, Papadimitriou, C, Papandreou, C, Papazisis, K, Castro, H, Hernandez-Monroy, C, Ngan, R, Yeo, W, Bittner, N, Boer, K, Csejtei, A, Horvath, Z, Kocsis, J, Mangel, L, Mezei, K, Nagy, Z, Szanto, J, Atmakusuma, D, Fadjari, H, Kurnianda, D, Prayogo, N, Tanggo, E, Coate, L, Hennessy, B, Kelly, C, Martin, M, Nasim, S, O'Connor, M, Aieta, M, Allegrini, G, Amadori, D, Bidoli, P, Biti, G, Bordonaro, R, Bottini, A, Carterni, G, Cavanna, L, Cazzaniga, M, Cognetti, F, Contu, A, Cruciani, G, Donadio, M, Falcone, A, Farci, D, Forcignano, R, Frassoldati, A, Gaion, F, Gamucci, T, Giotta, F, Livi, L, Lorusso, V, Maiello, E, Marchetti, P, Mariani, G, Mion, M, Moscetti, L, Musolino, A, Pazzola, A, Pedrazzoli, P, Pigi, A, de Placido, S, Caremoli, E, Santoro, A, Tienghi, A, Ahn, J, Lee, K, Lee, S, Seo, J, Sohn, J, Cesas, A, Juozaityte, E, Cheah, N, Chong, F, Devi, B, Phua, V, Teoh, D, Ching, L, Yusof, M, Corona, J, Dominguez, A, Mendoza, R, Hernandez, C, Ramiro, A, Santos, J, Espinosa, P, Villarreal Garza, C, Errihani, H, Bakker, S, van den Berkmortel, F, Blaisse, R, Huinink, D, van den Bosch, J, Braun, J, Dercksen, M, Droogendijk, H, Erdkamp, F, Haringhuizen, A, de Jongh, F, Kok, T, Los, M, Madretsma, S, Terwogt, J, van der Padt, A, van Rossum-Schornagel, Q, Smilde, T, de Valk, B, van der Velden, A, van Warmerdam, L, van de Wouw, A, North, R, Kersten, C, Mjaaland, I, Wist, E, Aziz, Z, Masood, N, Rashid, K, Shah, M, Alcedo, J, Aleman, D, Neciosup, S, Reategui, R, Valdiviezo, N, Vera, L, Fernando, G, Roque, F, Strebel, H, Krzemieniecki, K, Litwiniuk, M, Mruk, A, Pienkowski, T, Sawrycki, P, Slomian, G, Tomczak, P, Afonso, N, Cardoso, F, Damasceno, M, Nave, M, Badulescu, F, Ciule, L, Curescu, S, Eniu, A, Filip, D, Grecea, D, Jinga, D, Lungulescu, D, Oprean, C, Stanculeanu, D, Turdean, M, Dvornichenko, V, Emelyanov, S, Lichinitser, M, Manikhas, A, Sakaeva, D, Shirinkin, V, Stroyakovskiy, D, Abulkhair, O, Zekri, J, Filipovic, S, Kovcin, V, Nedovic, J, Pesic, J, Vasovic, S, Ng, R, Bystricky, B, Leskova, J, Mardiak, J, Misurova, E, Wagnerova, M, Takac, I, Demetriou, G, Dreosti, L, Govender, P, Jordaan, J, Veersamy, P, Romero, J, Lopez, N, Arias, C, Chacon, J, Aramburo, A, Morales, L, Garcia, M, Estevez, L, Garcia-Palomo Perez, A, Garcia Saenz, J, Garcia Sanchis, L, Cubells, L, Cortijo, L, Santiago, S, De Aranguiz, B, Manas, J, Gallego, P, Cussac, A, Ferrandiz, C, Garrido, M, Alvarez, P, Vega, J, Del Prado, P, Janez, N, Murillo, S, Rosales, A, Jaso, L, Fernandez, I, Martorell, A, Carrion, R, Simon, S, Alcibar, A, Lorenzo, J, Garcia, V, Asensio, T, Maicas, M, Villanueva Silva, M, Killander, F, Svensson, J, Fehr, M, Hauser, N, Muller, A, Pagani, O, Passmann-Kegel, H, Popescu, R, Rabaglio, M, Rauch, D, Schlatter, C, Zaman, K, Chang, T, Huang, C, Wang, H, Yu, J, Bandidwattanawong, C, Maneechavakajorn, J, Seetalarom, K, Dejthevaporn, T, Somwangprasert, A, Vongsaisuwon, M, Akbulut, H, Altundag, K, Arican, A, Bozcuk, H, Eralp, Y, Idris, M, Isikdogan, A, Senol, C, Sevinc, A, Uygun, K, Yucel, E, Yucel, I, Yumuk, F, Shparyk, Y, Voitko, N, Jaloudi, M, Adams, J, Agrawal, R, Ahmed, S, Alhasso, A, Allerton, R, Anwar, S, Archer, C, Ashford, R, Barraclough, L, Bertelli, G, Bishop, J, Branson, T, Butt, M, Chakrabarti, A, Chakraborti, P, Churn, M, Crowley, C, Davis, R, Dhadda, A, Eldeeb, H, Fraser, J, Hall, J, Hickish, T, Hogg, M, Howe, T, Joffe, J, Kelleher, M, Kelly, S, Kendall, A, Kristeleit, H, Lumsden, G, Macmillan, C, Macpherson, I, Malik, Z, Mithal, N, Neal, A, Panwar, U, Proctor, A, Proctor, S, Raj, S, Rehman, S, Sandri, I, Scatchard, K, Sherwin, E, Sims, E, Singer, J, Smith, S, Tahir, S, Taylor, W, Tsalic, M, Wardley, A, Waters, S, Wheatley, D, Wright, K, Yuille, F, Alonso, I, Artagaveytia, N, Rodriguez, R, Arbona, E, Garcia, Y, Lion, L, Marcano, D, and Van Thuan, T

Subjects
0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, Medizin, Antineoplastic Agent, 0302 clinical medicine, Breast cancer, Trastuzumab, Adjuvant, Aged, 80 and over, education.field_of_study, Middle Aged, HER2/neu, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Herceptin, Subcutaneous, subcutaneous, Female, Survival Analysi, Breast Neoplasm, medicine.drug, Human, Adult, medicine.medical_specialty, Injections, Subcutaneous, Population, Socio-culturale, Antineoplastic Agents, Breast Neoplasms, Injections, Subcutaneou, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Adjuvant therapy, Humans, Subcutaneou, education, Adverse effect, Aged, Chemotherapy, Adjuvant, breast cancer, HER2/neu, herceptin, trastuzumab, business.industry, medicine.disease, Survival Analysis, Surgery, Discontinuation, 030104 developmental biology, business
Abstract

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Published
2017

10. PR69 - LONG-TERM RESPONDERS WITH METASTATIC BREAST CANCER (MBC) RECEIVING ERIBULIN: REAL LIFE EXPERIENCE

Author

Zhukova, Ludmila, Gorbunova, Vera, Manzyuk, Ludmila, Kovalenko, Elena, Kalyadina, Irina, Bolotina, Larisa, Popova, Natalia, Golberg, Victor, Karandeeva, Tatiana, Alexey, Manikhas, Marfutov, Vasily, Filonenko, Dmitry, Vladimirova, Lubov, Tarasova, Anna, Shaidorov, Mikhail, Zhilyaeva, Ludmila, Ponomarenko, Dmitry, Karabina, Elena, Mukhametshina, Guzel, Khasanova, Alfia, Evstigneeva, Irina, and Chernyakova, Elena

Published
2019
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11. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer

Author

Cristina Oliva, M. John Kennedy, Gilles Romieu, Xavier Pivot, Michael F. Press, J. Maltzman, S. Stein, Stephen S. Johnston, L. O'Rourke, Henry L. Gomez, Mikhail Lichinitser, A. Florance, John Pippen, Alexey Manikhas, Saeed Sadeghi, Véronique Diéras, Mark D. Pegram, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
Oncology, MESH: Carcinoma, Cancer Research, Receptor, ErbB-2, Kaplan-Meier Estimate, MESH: Risk Assessment, MESH: Dose-Response Relationship, Drug, MESH: Proportional Hazards Models, 0302 clinical medicine, MESH: Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, MESH: Double-Blind Method, MESH: Kaplan-Meiers Estimate, skin and connective tissue diseases, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, Letrozole, MESH: Maximum Tolerated Dose, MESH: Neoplasm Staging, Middle Aged, MESH: Antineoplastic Agents, Hormonal, Prognosis, Metastatic breast cancer, MESH: Nitriles, 3. Good health, Postmenopause, MESH: Quinazolines, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Receptors, Estrogen, MESH: Receptor, erbB-2, 030220 oncology & carcinogenesis, MESH: Survival Analysis, MESH: Receptors, Estrogen, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Receptors, Progesterone, MESH: Postmenopause, medicine.drug, Adult, MESH: Receptors, Progesterone, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Maximum Tolerated Dose, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, Population, Breast Neoplasms, MESH: Drug Administration Schedule, Lapatinib, Risk Assessment, Disease-Free Survival, Drug Administration Schedule, MESH: Prognosis, 03 medical and health sciences, Breast cancer, Double-Blind Method, Internal medicine, Nitriles, medicine, Biomarkers, Tumor, Humans, Neoplasm Invasiveness, education, 030304 developmental biology, Aged, Neoplasm Staging, Proportional Hazards Models, Aromatase inhibitor, MESH: Humans, Dose-Response Relationship, Drug, business.industry, Carcinoma, MESH: Adult, MESH: Neoplasm Invasiveness, Triazoles, Antiestrogen, medicine.disease, Survival Analysis, Endocrinology, MESH: Triazoles, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, Quinazolines, business, MESH: Female, Tamoxifen, MESH: Breast Neoplasms
Abstract

PurposeCross-talk between human epidermal growth factor receptors and hormone receptor pathways may cause endocrine resistance in breast cancer. This trial evaluated the effect of adding lapatinib, a dual tyrosine kinase inhibitor blocking epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2), to the aromatase inhibitor letrozole as first-line treatment of hormone receptor (HR) –positive metastatic breast cancer (MBC).Patients and MethodsPostmenopausal women with HR-positive MBC were randomly assigned to daily letrozole (2.5 mg orally) plus lapatinib (1,500 mg orally) or letrozole and placebo. The primary end point was progression-free survival (PFS) in the HER2-positive population.ResultsIn HR-positive, HER2-positive patients (n = 219), addition of lapatinib to letrozole significantly reduced the risk of disease progression versus letrozole-placebo (hazard ratio [HR] = 0.71; 95% CI, 0.53 to 0.96; P = .019); median PFS was 8.2 v 3.0 months, respectively. Clinical benefit (responsive or stable disease ≥ 6 months) was significantly greater for lapatinib-letrozole versus letrozole-placebo (48% v 29%, respectively; odds ratio [OR] = 0.4; 95% CI, 0.2 to 0.8; P = .003). Patients with centrally confirmed HR-positive, HER2-negative tumors (n = 952) had no improvement in PFS. A preplanned Cox regression analysis identified prior antiestrogen therapy as a significant factor in the HER2-negative population; a nonsignificant trend toward prolonged PFS for lapatinib-letrozole was seen in patients who experienced relapse less than 6 months since prior tamoxifen discontinuation (HR = 0.78; 95% CI, 0.57 to 1.07; P = .117). Grade 3 or 4 adverse events were more common in the lapatinib-letrozole arm versus letrozole-placebo arm (diarrhea, 10% v 1%; rash, 1% v 0%, respectively), but they were manageable.ConclusionThis trial demonstrated that a combined targeted strategy with letrozole and lapatinib significantly enhances PFS and clinical benefit rates in patients with MBC that coexpresses HR and HER2.

Published
2009
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12. A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer.

Author

August Garin, Alexey Manikhas, Mikhail Biakhov, Mikhail Chezhin, Tatiana Ivanchenko, Kurt Krejcy, and Sergey Tjulandin

Subjects
BREAST cancer, METASTASIS, DRUG synergism, DRUG therapy
Abstract

Abstract Background   Pemetrexed and carboplatin have demonstrated activity in breast cancer. Their potential synergism in experimental models and the proven efficacy of pemetrexed/platinum in other indications make pemetrexed/carboplatin an attractive combination in breast cancer. Thus, this two-stage, sequential, open-label, multicenter, phase II study assessed the efficacy and safety of pemetrexed plus carboplatin as first-line therapy in patients with locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). Patients and methods   Patients ≥ 18 years with a histologic/cytologic diagnosis and no prior chemotherapy for LABC or MBC received pemetrexed 600 mg/m2 and carboplatin AUC 5.0 on day 1 every 21 days with folic acid and vitamin B12 supplementation. Results  From June 2003 to April 2005, 50 patients with stage IIIB (30.0%) and stage IV (70.0%) disease were enrolled at 3 study centers. Twenty-eight percent of patients previously received adjuvant chemotherapy, 46.0% had visceral metastases, and 36.0% had ≥3 organs involved. Partial responses (RECIST criteria) were achieved in 27 (54.0%) patients (ORR = 54.0%; 95% CI, 39.3–68.2%). The median response duration was 11.1 months (95% CI, 6.5–14.0 months) and the median time to disease progression was 10.3 months (95% CI, 8.3–14.6 months). CTC hematologic toxicities were grade 3/4 neutropenia (58.0%/28.0%) and grade 3 thrombocytopenia (10.0%) and anemia (18.0%). Two (4.0%) patients had febrile neutropenia, 1 of whom died. No grade 4 non-hematologic toxicities occurred. Grade 3 non-hematologic toxicities were ALT (4.0%) and AST elevation, and edema, fatigue, pruritus, rash/desquamation, and renal toxicity (2.0% each). Conclusions   Results of this study suggest that the combination of pemetrexed and carboplatin has promising efficacy and an acceptable safety profile. Further assessment of this combination in a randomized trial of various breast cancer patient populations is warranted. [ABSTRACT FROM AUTHOR]

Published
2008
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13. CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

Author

Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, and Semiglazov V

Subjects
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized administration & dosage, Breast Neoplasms pathology, Breast Neoplasms prevention & control, Capecitabine, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Disease-Free Survival, Drug Administration Schedule, Female, Fluorouracil administration & dosage, Fluorouracil analogs & derivatives, Humans, Infusions, Intravenous, Kaplan-Meier Estimate, Lapatinib, Middle Aged, Neoplasm Recurrence, Local prevention & control, Neoplasm Staging, Odds Ratio, Quinazolines administration & dosage, Trastuzumab, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor analysis, Breast Neoplasms chemistry, Breast Neoplasms drug therapy, Receptor, ErbB-2 analysis
Abstract

Purpose: CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine., Patients and Methods: Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m(2) per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m(2) per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS)., Results: The study was terminated early with 540 enrolled patients (271 received lapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively., Conclusion: CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting., (© 2015 by American Society of Clinical Oncology.)

Published
2015
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14. Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31.

Author

Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, and Parulekar WR

Subjects
Adult, Aged, Antibodies, Monoclonal, Humanized administration & dosage, Breast Neoplasms pathology, Bridged-Ring Compounds administration & dosage, Diarrhea chemically induced, Disease-Free Survival, Drug Administration Schedule, Drug Eruptions etiology, Female, Follow-Up Studies, Humans, International Cooperation, Kaplan-Meier Estimate, Lapatinib, Middle Aged, Neoplasm Staging, Patient Selection, Quality of Life, Quinazolines administration & dosage, Quinazolines adverse effects, Taxoids administration & dosage, Trastuzumab, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor analysis, Breast Neoplasms chemistry, Breast Neoplasms drug therapy, Receptor, ErbB-2 analysis
Abstract

Purpose: The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown., Patients and Methods: The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors., Results: From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03)., Conclusion: As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane., (© 2015 by American Society of Clinical Oncology.)

Published
2015
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15. Primary results of ROSE/TRIO-12, a randomized placebo-controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer.

Author

Mackey JR, Ramos-Vazquez M, Lipatov O, McCarthy N, Krasnozhon D, Semiglazov V, Manikhas A, Gelmon KA, Konecny GE, Webster M, Hegg R, Verma S, Gorbunova V, Abi Gerges D, Thireau F, Fung H, Simms L, Buyse M, Ibrahim A, and Martin M

Subjects
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Disease-Free Survival, Docetaxel, Double-Blind Method, Drug Administration Schedule, Fatigue chemically induced, Febrile Neutropenia chemically induced, Female, Hand-Foot Syndrome etiology, Humans, Hypertension chemically induced, Immunoglobulin G, Kaplan-Meier Estimate, Middle Aged, Stomatitis chemically induced, Taxoids administration & dosage, Taxoids adverse effects, Treatment Outcome, Ramucirumab, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Neoplasm Recurrence, Local drug therapy
Abstract

Purpose: Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, locally recurrent, or metastatic breast cancer., Patients and Methods: In this double-blind, placebo-controlled, randomized, multinational phase III trial, 1,144 patients with human epidermal growth factor receptor 2 (HER2) -negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomly assigned at a two-to-one ratio to receive docetaxel 75 mg/m(2) plus ramucirumab 10 mg/kg or docetaxel 75 mg/m(2) plus placebo once every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographic region. An independent data monitoring committee oversaw the trial. The primary end point was investigator-assessed PFS., Results: Median PFS in patients treated with ramucirumab plus docetaxel was 9.5 months, compared with 8.2 months in patients who received placebo plus docetaxel (hazard ratio [HR], 0.88; P = .077). Median overall survival was 27.3 months in patients who received ramucirumab plus docetaxel, compared with 27.2 months in patients who received placebo plus docetaxel (HR, 1.01; P = .915). Toxicities seen at significantly higher rates in patients receiving ramucirumab included fatigue, hypertension, febrile neutropenia, palmar-plantar erythrodysesthesia syndrome, and stomatitis., Conclusion: Addition of ramucirumab to docetaxel in HER2-negative advanced breast cancer did not meaningfully improve important clinical outcomes., (© 2014 by American Society of Clinical Oncology.)

Published
2015
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