Pertuzumab and Trastuzumab: Re-Responses to 2 Biological Agents in Patients with HER2-Positive Breast Cancer Which Had Previously Progressed during Therapy with Each Agent Given Separately: A New Biological and Clinical Observation.
Notice bibliographique
Résumé
Abstract Background: Pertuzumab, a fully humanised IgG1 monoclonal antibody, is a human epidermal growth factor receptor 2 (HER2)-dimerisation inhibitor directed to the dimerisation epitope of HER2 (trastuzumab binds to the juxta-membrane epitope). Pertuzumab has demonstrated promising activity when given with trastuzumab to patients with HER2-positive metastatic breast cancer (mBC) which had progressed during therapy with trastuzumab in a 2-step Phase II study.1Methods: The protocol was amended to include a 3rd cohort of patients to determine the activity of pertuzumab when given without trastuzumab.2 Patients recruited into this 3rd cohort were allowed to have trastuzumab re-introduced in combination with pertuzumab if there was inadequate response to pertuzumab alone or response followed by relapse.Results: Twenty-nine patients were recruited into this 3rd cohort. Patients had reached their 3rd line of treatment for mBC. To date, 15 patients have had trastuzumab re-introduced after disease progression on trastuzumab therapy and pertuzumab monotherapy. Among these 15 patients, at the time of this analysis there have been 3 patients with confirmed responses. There are also 4 patients who had not yet undergone 8 cycles of assessments to reach the overall best response end point, of which at least 2 were experiencing stablisation of disease. Updated data on activity and toxicity will be presented.Conclusions: We believe this is the first time that anti-tumour activity has been reported in patients when 2 biological agents have been used together after the disease has progressed during therapy with each agent alone. There are several mechanisms which might explain this phenomenon. Trastuzumab prevents proteolytic cleavage of the extracellular domain of HER2, keeping the receptor in situ. The addition of a second antibody to a separate epitope increases the potential for antibody-dependent cell-mediated cytotoxicity and prevents dimerisation between HER2 and other HER family members, such as HER1 and HER3. The combined antibodies might increase the efficiency of inhibition of signal transduction. There are wide-ranging and potentially significant biological and clinical implications. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5114.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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