Comparative efficacy and safety of trastuzumab biosimilars to the reference drug: a systematic review and meta-analysis of randomized clinical trials.

Biosimilar Pharmaceuticals / administration & dosage Breast Neoplasms / drug therapy Clinical Trials, Phase III as Topic Equivalence Trials as Topic Female Heart Failure / chemically induced Humans Infusions, Intravenous / adverse effects Injection Site Reaction Intention to Treat Analysis Neutropenia / chemically induced Receptor, ErbB-2 / antagonists & inhibitors Survival Rate Trastuzumab / administration & dosage Treatment Outcome
Biosimilars Efficacy Meta-analysis Randomized clinical trials Safety Trastuzumab

Journal

Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519

Informations de publication

Date de publication:
11 2020
Historique:
received: 30 07 2020
accepted: 24 09 2020
pubmed: 3 10 2020
medline: 21 5 2021
entrez: 2 10 2020
Statut: ppublish

Résumé

To assess efficacy and safety of trastuzumab biosimilars in comparison to the reference drug through a systematic review and meta-analysis of randomized controlled trials (RCTs). A comprehensive search was conducted using PubMed, Web of Science, Cochrane library, Open Grey and ClinicalTrials.gov databases. Dichotomous data for efficacy and safety outcomes were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs). Meta-analysis was performed with the Mantel-Haenszel method using Revman 5.3 software. Eight phase III RCTs including a total of 3913 patients with HER2 + breast cancer were identified that met the inclusion criteria. The pooled results for the comparison of trastuzumab biosimilars to the reference drug showed no differences of objective response rate (ORR) (RR 1.05, 95% CI 0.98-1.12, P = 0.20) or overall survival (RR 0.82, 95% CI 0.61-1.09, P = 0.17) in the intention-to-treat population, as well as no difference of ORR (RR 1.03, 95% CI 0.97-1.10, P = 0.30) in the per-protocol population. Similarly, no significant difference was detected in any type of adverse event reported in at least three RCTs, including any serious treatment-emergent adverse effects (RR 0.97, 95% CI 0.76-1.25, P = 0.83), heart failure (RR 1.47, 95% CI 0.69-3.14, P = 0.32), neutropenia (RR 1.05, 95% CI 0.96-1.15, P = 0.26), and infusion-related reaction (RR 1.10, 95% CI 0.89-1.36, P = 0.38). This meta-analysis provides compelling evidence of clinical comparability between trastuzumab biosimilars and the originator product in terms of both efficacy and safety for the treatment of HER2 + breast cancer.

Identifiants

DOI: 10.1007/s00280-020-04156-3 PMID: 33005979
pubmed: 33005979
doi: 10.1007/s00280-020-04156-3
pii: 10.1007/s00280-020-04156-3
doi:

Substances chimiques

Biosimilar Pharmaceuticals 0
ERBB2 protein, human EC 2.7.10.1
Receptor, ErbB-2 EC 2.7.10.1
Trastuzumab P188ANX8CK

Types de publication

Comparative Study Journal Article Meta-Analysis Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

577-588

Références

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
doi: 10.3322/caac.21492
Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, Bonaventure A, Valkov M, Johnson CJ, Estève J, Ogunbiyi OJ, Azevedo E, Silva G, Chen WQ, Eser S, Engholm G, Stiller CA, Monnereau A, Woods RR, Visser O, Lim GH, Aitken J, Weir HK, Coleman MP, CONCORD Working Group (2018) Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 17(391):1023–1075. https://doi.org/10.1016/S0140-6736(17)33326-3
doi: 10.1016/S0140-6736(17)33326-3
Zeng H, Chen W, Zheng R, Zhang S, Ji JS, Zou X, Xia C, Sun K, Yang Z, Li H, Wang N, Han R, Liu S, Li H, Mu H, He Y, Xu Y, Fu Z, Zhou Y, Jiang J, Yang Y, Chen J, Wei K, Fan D, Wang J, Fu F, Zhao D, Song G, Chen J, Jiang C, Zhou X, Gu X, Jin F, Li Q, Li Y, Wu T, Yan C, Dong J, Hua Z, Baade P, Bray F, Jemal A, Yu XQ, He J (2018) Changing cancer survival in China during 2003–15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health 6:e555–e567. https://doi.org/10.1016/S2214-109X(18)30127-X
doi: 10.1016/S2214-109X(18)30127-X
Malvezzi M, Carioli G, Bertuccio P, Boffetta P, Levi F, La Vecchia C, Negri E (2019) European cancer mortality predictions for the year 2019 with focus on breast cancer. Ann Oncol 30:781–787. https://doi.org/10.1093/annonc/mdz051
doi: 10.1093/annonc/mdz051
Fabi A, Malaguti P, Vari S, Cognetti F (2016) First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces? J Exp Clin Cancer Res 35:104. https://doi.org/10.1186/s13046-016-0380-5
doi: 10.1186/s13046-016-0380-5
Kast K, Schoffer O, Link T, Forberger A, Petzold A, Niedostatek A, Werner C, Klug SJ, Werner A, Gatzweiler A, Richter B, Baretton G, Wimberger P (2017) Trastuzumab and survival of patients with metastatic breast cancer. Arch Gynecol Obstet 296:303–312. https://doi.org/10.1007/s00404-017-4421-x
doi: 10.1007/s00404-017-4421-x
US FDA. Full Prescribing Information for Herceptin (Trastuzumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103792s5250lbl.pdf . Accessed 15 Jul 2020
EMA. European Public Assessment Report of Herceptin (Trastuzumab). https://www.ema.europa.eu/en/documents/product-information/herceptin-epar-product-information_en.pdf . Accessed 15 Jul 2020
World Health Organization. WHO model list of essential medicines: 19th list. https://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1 . Accessed 15 Jul 2020
Blackwell K, Gligorov J, Jacobs I, Twelves C (2018) The global need for a trastuzumab biosimilar for patients with HER2-positive breast cancer. Clin Breast Cancer 18:95–113. https://doi.org/10.1016/j.clbc.2018.01.006
doi: 10.1016/j.clbc.2018.01.006
Lammers P, Criscitiello C, Curigliano G, Jacobs I (2014) Barriers to the use of trastuzumab for HER2+ breast cancer and the potential impact of biosimilars: a physician survey in the United States and emerging markets. Pharmaceuticals (Basel) 7:943–953. https://doi.org/10.3390/ph7090943
doi: 10.3390/ph7090943
Cherny N, Sullivan R, Torode J, Saar M, Eniu A (2016) ESMO European Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in Europe. Ann Oncol 27:1423–1443. https://doi.org/10.1093/annonc/mdw213
doi: 10.1093/annonc/mdw213
Chavarri-Guerra Y, St Louis J, Bukowski A, Soto-Perez-de-Celis E, Liedke PER, Symecko H, Moy B, Higgins M, Finkelstein DM, Goss PE (2017) Real world patterns of care in HER2-overexpressing breast cancer: results of a survey of TEACH Clinical Trial Investigators in 2011. Breast 31:197–201. https://doi.org/10.1016/j.breast.2016.11.014
doi: 10.1016/j.breast.2016.11.014
US FDA. Full Prescribing Information for Kanjinti (Trastuzumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761073s000lbl.pdf . Accessed 15 Jul 2020
US FDA. Full Prescribing Information for Herzuma (Trastuzumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761091s000lbl.pdf . Accessed 15 Jul 2020
US FDA. Full Prescribing Information for Ontruzant (Trastuzumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761100s000lbl.pdf . Accessed 15 Jul 2020
US FDA. FDA-Approved Biosimilar Products list including Trazimera (Trastuzumab). https://www.fda.gov/drugs/biosimilars/biosimilar-product-information . Accessed 15 Jul 2020
US FDA. Full Prescribing Information for Ogivri (Trastuzumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761074s000lbl.pdf . Accessed 15 Jul 2020
EMA. European Public Assessment Report of Kanjinti (Trastuzumab). https://www.ema.europa.eu/en/documents/product-information/kanjinti-epar-product-information_it.pdf . Accessed 15 Jul 2020
EMA. European Public Assessment Report of Herzuma (Trastuzumab). https://www.ema.europa.eu/en/documents/product-information/herzuma-epar-product-information_en.pdf . Accessed 15 Jul 2020
EMA. European Public Assessment Report of Ontruzant (Trastuzumab). https://www.ema.europa.eu/en/documents/product-information/ontruzant-epar-product-information_it.pdf . Accessed 15 Jul 2020
EMA. European Public Assessment Report of Trazimera (Trastuzumab). https://www.ema.europa.eu/en/documents/product-information/trazimera-epar-product-information_en.pdf . Accessed 15 Jul 2020
EMA. European Public Assessment Report of Ogivri (Trastuzumab). https://www.ema.europa.eu/en/documents/product-information/ogivri-epar-product-information_en.pdf . Accessed 15 Jul 2020
Busse A, Lüftner D (2019) What does the pipeline promise about upcoming biosimilar antibodies in oncology? Breast Care (Basel) 14:10–16. https://doi.org/10.1159/000496834
doi: 10.1159/000496834
Thill M (2019) Biosimilar trastuzumab in clinical trials: differences or not? Breast Care (Basel) 14:17–22. https://doi.org/10.1159/000496503
doi: 10.1159/000496503
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097
doi: 10.1371/journal.pmed.1000097
Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods Group; Cochrane Statistical Methods Group (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://doi.org/10.1136/bmj.d5928
doi: 10.1136/bmj.d5928
Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1:97–111. https://doi.org/10.1002/jrsm.12
doi: 10.1002/jrsm.12
Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826
doi: 10.7326/0003-4819-127-9-199711010-00008
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557
doi: 10.1136/bmj.327.7414.557
Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, Carpenter J, Rücker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002. https://doi.org/10.1136/bmj.d4002
doi: 10.1136/bmj.d4002
von Minckwitz G, Colleoni M, Kolberg HC, Morales S, Santi P, Tomasevic Z, Zhang N, Hanes V (2018) Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol 19:987–998. https://doi.org/10.1016/S1470-2045(18)30241-9
doi: 10.1016/S1470-2045(18)30241-9
Esteva FJ, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskiy D, Pikiel J, Eniu AE, Li RK, Rusyn AV, Tiangco B, Lee SJ, Lee SY, Yu SY, Stebbing J (2019) Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial. Cancer Chemother Pharmacol 84:839–847. https://doi.org/10.1007/s00280-019-03920-4
doi: 10.1007/s00280-019-03920-4
Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Shparyk Y, Moiseyenko V, Bello M 3rd, Semiglazov V, Lee Y, Lim J (2018) A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumabreference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: final safety, immunogenicity and survival results. Eur J Cancer 93:19–27. https://doi.org/10.1016/j.ejca.2018.01.072
doi: 10.1016/j.ejca.2018.01.072
Lammers PE, Dank M, Masetti R, Abbas R, Hilton F, Coppola J, Jacobs I (2018) Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer 119:266–273. https://doi.org/10.1038/s41416-018-0147-1
doi: 10.1038/s41416-018-0147-1
Pegram MD, Bondarenko I, Zorzetto MMC, Hingmire S, Iwase H, Krivorotko PV, Lee KS, Li RK, Pikiel J, Aggarwal R, Ewesuedo R, Freyman A, Li R, Vana A, Yin D, Zacharchuk C, Tan-Chiu E (2019) PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumabplus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer 120:172–182. https://doi.org/10.1038/s41416-018-0340-2
doi: 10.1038/s41416-018-0340-2
Rugo HS, Barve A, Waller CF, Hernandez-Bronchud M, Herson J, Yuan J, Sharma R, Baczkowski M, Kothekar M, Loganathan S, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng ML, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Ray S, Yanez Ruiz EP, Pennella E, Heritage Study Investigators (2017) Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2)-positive metastatic breast cancer: a randomized clinical trial. JAMA 317:37–47. https://doi.org/10.1001/jama.2016.18305
doi: 10.1001/jama.2016.18305
Apsangikar P, Chaudhry S, Naik M, Deoghare S, Joseph J (2017) A comparative phase III clinical study to evaluate efficacy and safety of TrastuRel™ (biosimilar trastuzumab) and innovator trastuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. Indian J Cancer 54:664–668. https://doi.org/10.4103/ijc.IJC_449_17
doi: 10.4103/ijc.IJC_449_17
Clinicaltrials.gov. A safety and efficacy study of BCD-022 with paclitaxel compared to Herceptin with paclitaxel in HER2+ metastatic breast cancer. https://clinicaltrials.gov/ct2/show/study/NCT01764022 . Accessed 15 Jul 2020
Lemery SJ, Stacey Ricci M, Keegan P, McKee AE, Richard Pazdur P (2017) FDA’s approach to regulating biosimilars. Clin Cancer Res 23:1882–1885. https://doi.org/10.1158/1078-0432.CCR-16-1354
doi: 10.1158/1078-0432.CCR-16-1354
Weise M, Bielsky MC, De Smet K, Ehmann F, Ekman N, Giezen TJ, Gravanis I, Heim HK, Heinonen E, Ho K, Moreau A, Narayanan G, Kruse NA, Reichmann G, Thorpe R, van Aerts L, Vleminckx C, Wadhwa M, Schneider CK (2012) Biosimilars: what clinicians should know. Blood 120:5111–5117. https://doi.org/10.1182/blood-2012-04-425744
doi: 10.1182/blood-2012-04-425744
Kolberg HC, Colleoni M, Santi P, Savva Demetriou G, Segui-Palmer MA, Fujiwara Y, Sara A, Hurvitz SA, Hanes V (2019) Totality of scientific evidence in the development of ABP 980, a biosimilar to trastuzumab. Target Oncol 14:647–656. https://doi.org/10.1007/s11523-019-00675-z
doi: 10.1007/s11523-019-00675-z
European Medicines Agency (2012) Guideline on similar biological medicinal products containing monoclonal antibodies—non-clinical and clinical issues. https://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500128686.pdf . Accessed 15 Jul 2020
Schulz KF, Altman DG, Moher D, CONSORT Group (2010) CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. PLoS Med 7:e1000251. https://doi.org/10.1371/journal.pmed.1000251
doi: 10.1371/journal.pmed.1000251
Schumi J, Wittes JT (2011) Through the looking glass: understanding non inferiority. Trials 12:106. https://doi.org/10.1186/1745-6215-12-106
doi: 10.1186/1745-6215-12-106
European Medicines Agency. Assessment report for Herceptin (trastuzumab). https://www.ema.europa.eu/en/documents/variation-report/herceptin-h-c-278-ii-0057-epar-assessment-report-variation_en.pdf . Accessed 15 Jul 2020
US Food & Drug Administration. Guidance for industry. Immunogenicity assessment for therapeutic protein products. 2014. https://www.fda.gov/media/85017/download . Accessed 15 Jul 2020
Pivot X, Pegram M, Cortes J, Lüftner D, Lyman GH, Curigliano G, Bondarenko I, Yoon YC, Kim Y, Kim C (2019) Three-year follow-up from a phase 3 study of SB3 (a trastuzumab biosimilar) versus reference trastuzumab in the neoadjuvant setting for human epidermal growth factor receptor 2-positive breast cancer. Eur J Cancer 120:1–9. https://doi.org/10.1016/j.ejca.2019.07.015
doi: 10.1016/j.ejca.2019.07.015
Yang J, Yu S, Yang Z, Yan Y, Chen Y, Zeng H, Ma F, Shi Y, Shi Y, Zhang Z, Sun F (2019) Efficacy and safety of anti-cancer biosimilars compared to reference biologics in oncology: a systematic review and meta-analysis of randomized controlled trials. BioDrugs 33:357–371. https://doi.org/10.1007/s40259-019-00358-1
doi: 10.1007/s40259-019-00358-1
Kolberg HC, Demetriou GS, Zhang N, Tomasevic Z, Hanes V (2018) Safety results from a randomized, double-blind, phase 3 study of ABP 980 compared with trastuzumab in patients with breast cancer. Cancer Res. https://doi.org/10.1158/15387445.sabcs17-pd3-10
doi: 10.1158/15387445.sabcs17-pd3-10
Esteva FJ, Baranau Y, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskiy D, Pikiel J, Eniu A, Komov D, Zautashvili Z, Morar-Bolba G, Li RK, Lifirenko I, Rusyn A, Lee SJ, Yu S, Stebbing J (2017) Double-blind, randomized phase III study to compare the efficacy and safety of trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early breast cancer (EBC). Ann Oncol 28:v44–45. https://doi.org/10.1093/annonc/mdx362.003
doi: 10.1093/annonc/mdx362.003
Anonymous (2016) Trial validates biosimilar for trastuzumab. Cancer Discov 6:686–687. https://doi.org/10.1158/2159-8290
doi: 10.1158/2159-8290
Puértolas-Tena I, Frutos Pérez-Surio A (2019) Comment on: “efficacy and safety of supportive care biosimilars among cancer patients: a systematic review and meta-analysis”. BioDrugs 33:583–584. https://doi.org/10.1007/s40259-019-00383-0
doi: 10.1007/s40259-019-00383-0
Yang J, Yu S, Yang Z, Yan Y, Chen Y, Zeng H, Ma F, Shi Y, Shi Y, Zhang Z, Sun F (2019) Efficacy and safety of supportive care biosimilars among cancer patients: a systematic review and meta-analysis. BioDrugs 33(4):373–389. https://doi.org/10.1007/s40259-019-00356-3
doi: 10.1007/s40259-019-00356-3

Auteurs

Sarah Cargnin (S)

Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2, 28100, Novara, Italy.

Jae Il Shin (JI)

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.

Armando A Genazzani (AA)

Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2, 28100, Novara, Italy.

Alessia Nottegar (A)

Pathology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), 37134, Verona, Italy.

Salvatore Terrazzino (S)

Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2, 28100, Novara, Italy. salvatore.terrazzino@uniupo.it.
ORCID: 0000-0002-4909-1121

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Mélanges complexes › Produits biologiques › Produits pharmaceutiques biosimilaires › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques de phase III comme sujet › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques contrôlés comme sujet › Essais contrôlés randomisés comme sujet › Essais d'équivalence comme sujet › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Défaillance cardiaque › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Perfusions parentérales › Perfusions veineuses › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Troubles dus à des produits chimiques › Effets secondaires indésirables des médicaments › Réaction au site d'injection › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques contrôlés comme sujet › Essais contrôlés randomisés comme sujet › Analyse en intention de traitement › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Troubles leucocytaires › Leucopénie › Agranulocytose › Neutropénie › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Récepteur ErbB-2 › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Mortalité › Taux de survie › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Trastuzumab › Comparative efficacy and safety of trastuzumab...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Comparative efficacy and safety of trastuzumab...