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.
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".