Abstract P1-08-42: High HER2 expression correlates with response to trastuzumab and the combination of trastuzumab and lapatinib in the NeoALTTO phase III trial
| Autor: | H Eidtmann, Ludmila Prudkin, M Scaltriti, J. Baselga, Jeff Sperinde, Catherine E. Ellis, Nadia Harbeck, M.J. Piccart, Josep Lluis Parra, Violeta Serra, Ian Bradbury, Paolo Nuciforo, Joaquín Arribas, Lajos Pusztai |
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| Rok vydání: | 2013 |
| Předmět: |
Response rate (survey)
Oncology Cancer Research medicine.medical_specialty Pathology business.industry Cancer Lapatinib medicine.disease Metastatic breast cancer chemistry.chemical_compound Paclitaxel chemistry Trastuzumab Hormone receptor Internal medicine Medicine skin and connective tissue diseases business neoplasms Pathological medicine.drug |
| Zdroj: | Cancer Research. 73:P1-08 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Background: Expression of p95HER2, a truncated form of HER2 lacking the extracellular domain, has been associated with resistance to trastuzumab (T)-based therapy in metastatic breast cancer patients. Conversely, high levels of HER2 have been correlated with increased clinical benefit from anti-HER2 therapy in the neoadjuvant setting. In this work we correlated the expression of p95HER2 and HER2 with pathological complete response (pCR) following T, lapatinib (L) or the combination of both agents (T+L) with paclitaxel. Methods: p95HER2 and HER2 were quantified by VeraTag® and HERmark® (Monogram Biosciences), respectively, in primary tumors of 455 patients enrolled in the phase III neoadjuvant study NeoALTTO (Baselga J. et al. Lancet, 2012). The relationship of pCR status to p95HER2 and HER2 was studied using logistic regression models, which accounted for stratification factors and treatment. Unless specified, p95HER2 and HER2 were included as log terms. Results: p95HER2 was measurable in 283 cases (62%) and HER2 in 327 cases (72%). A positive correlation between p95HER2 and HER2 levels was found in the 274 cases (60%) where quantification of both markers was available. Increased HER2 was strongly associated with increased pCR rate in patients treated with the combination of T+L (OR 5.09, 95%CI 2.27-11.44; p17.8 RF/mm2) by HERmark had a higher pCR rate than those that were HER2-negative by HERmark (39% vs. 11%, respectively; p In an unplanned analysis, we examined the odds of achieving response to anti-HER2 therapy in patients with HER2 levels above and below the median (100 RF/mm2, HER2 entered as a binary covariate). HER2 levels above the median predicted a higher response rate to T (OR 3.6, 95% CI 1.2-11; p0.2; OR 1.84, 95% CI 0.74-4.55). When tumors were divided in hormone receptor (HR)-positive and HR-negative groups, total levels of HER2 still predicted response to T or T+L. Conclusions: Increasing HER2 protein expression correlated with increased benefit of adding L to T compared to T alone. In tumors above the median of HER2 expression, the levels of HER2 predicted for response to both T and T+L. Our interpretation is that, in the neoadjuvant setting, the association between p95HER2 expression and response to anti-HER2 therapy is likely a consequence of the correlation between p95HER2 and total HER2 levels. HER2 expression seems to be a stronger predictor of pCR than p95HER2 for response to T, L and especially, T+L. Future studies to understand the impact of p95HER2 and HER2 expression on disease-free and overall survival following anti-HER2 therapy are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-42. |
| Databáze: | OpenAIRE |
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