Showing papers by "Günther G. Steger published in 2011"

Oncologic safety of breast conserving surgery after tumour downsizing by neoadjuvant therapy: a retrospective single centre cohort study

Abstract: The objective of this study is to analyse local recurrence rates in patients receiving neoadjuvant chemotherapy (nCT) comparing mastecomized (MX) patients with those undergoing breast conserving therapy (BCT). Patients undergoing breast cancer surgery after nCT (3xCMF or 3-6xED) between 1995 and 2007 at our department were retrospectively analysed. The median follow up was 60 months for 308 patients. Patients who were downsized from MX to BCT with partial or complete response (n = 104) had a similar local recurrence free survival (LRFS) compared to patients who did not experience successful downsizing (n = 67) and finally undergoing MX (LRFS MX-BCT 81% vs. MX-MX 91%; P = 0.79). Uni- and multivariate analyses demonstrated that BCT itself was not an independent prognostic factor for a worse LRFS (P = 0.07 and 0.14). After no pathologic change or progressive disease the risk of local recurrence was increased in patients undergoing BCT (MX-BCT; n = 6 LRFS 66%) compared with MX (n = 44; LRFS 90%; P = 0.04). Overall survival in general was better for the BCT group (n = 197) compared with MX group (n = 111) regardless of clinical response (92% vs. 72%; P < 0.0001). Breast conservation, nodal negativity and low or medium grade histology were prognostic factors for an improved OS (P = 0.02, 0.01, 0.004). In conclusion, our study suggests that BCT is oncologically safe after tumour downsizing by nCT in patients primarily scheduled for mastectomy. These patients, however, should not be treated with breast conservation in the absence of any proven response after nCT.

Single-agent pegylated liposomal doxorubicin (PLD) in the treatment of metastatic breast cancer: results of an Austrian observational trial.

Abstract: In advanced breast cancer, multiple sequential lines of treatments are frequently applied. Pegylated liposomal doxorubicin (PLD) has a favourable toxicity profile and can be used in first or higher lines of therapy. PLD has demonstrated response activity even after prior anthracycline exposure. 129 consecutive patients with advanced breast cancer, of whom the majority had been massively pretreated, received PLD as monotherapy within licensed approval, for which efficacy and toxicities were documented. In a routine therapy setting, PLD was administered in a slightly reduced dose (median, 40 mg/m2 per cycle). Response rate (complete and partial remission) was 26%, and stable disease was observed in 19% of patients. Progression-free (PFS) and overall survival (OS) were 5.8 months and 14.2 months, respectively. There was no difference in terms of response and PFS, no matter if patients had already received anthracycline treatment. Interestingly, PFS proved similar regardless whether PLD was administered as palliative therapy in first, second or third line. Furthermore, PFS and OS were similar in patients with response or stable disease, underscoring the view that disease stabilization is associated with a profound clinical benefit. The most common side effects reported were palmar-plantar erythrodysesthesia (17%), exanthema (14%) and mucositis (12%). Efficacy and toxicity data in these "real life" patients permit the conclusion that PLD is a valuable option in the treatment of advanced breast cancer even in heavily pretreated patients.

P3-16-07: Denosumab in Patients with Breast Cancer and Bone Metastases Previously Treated with Zoledronic Acid or Denosumab: Results from the 2-Year Open-Label Extension Treatment Phase of a Pivotal Phase 3 Study.

Abstract: Background Primary results from a phase 3, randomized, double-blind double-dummy trial showed that compared with zoledronic acid (ZA), denosumab reduced the risk of developing a first on-study SRE by 18% (hazard ratio, 0.82; 95% CI 0.71 to 0.95; P = 0.01), and the risk of multiple SREs by 23% (rate ratio, 0.77; 95% CI 0.66 to 0.89; P = 0.001) in patients with breast cancer and bone metastases. Based on superior efficacy and favorable safety data from the study9s primary analysis (Stopeck et al, 2010), all patients who remained on treatment were offered open-label denosumab in a prespecified 2-year extension treatment phase. Materials and Methods : A total of 2046 patients with breast cancer and bone metastasis were randomized to receive either subcutaneous (SC) denosumab 120 mg and intravenous (IV) placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the double-blinded treatment phase. Patients who completed the double-blinded treatment phase were offered open-label denosumab Q4W for up to 2 years from the start of the open-label treatment phase. Patients who did not participate in the open-label treatment were followed for survival every 12 weeks for up to 2 years after their last dose of investigational product in the double-blinded treatment phase. Results : Of the 752 patients who completed the double-blinded treatment phase, 667 (89%) patients entered the open-label treatment phase: 325 (48.7%) initially randomized to the denosumab group (DD) and 342 (51.3%) to the ZA group in the double-blinded treatment phase (ZD). Demographics were comparable between groups. The total median (Q1, Q3) cumulative denosumab exposure (including double-blinded and open-label treatment phases) for DD patients was 19.3 months (9.2, 32.2) (range 0.9−59.8 months). Adverse events (AEs) were comparable between groups (n = 283/318 [89%] for DD patients; n = 303/334 [91%] ZD patients). An additional 20 patients in the DD group and 18 patients in the ZD group reported osteonecrosis of the jaw, resulting in a cumulative incidence of 4.7% for DD patients and 3.5% for ZD patients for the entire study duration of 5 years. Hypocalcemia AEs during the open-label treatment phase were comparable between groups (n = 12 DD; n = 9 ZD). The most common AEs were nausea, fatigue, and back pain. Serious AEs were reported in 126 (39.6%) DD patients and 133 (39.8%) ZD patients. Overall survival was similar between groups over the entire study: median 34.4 months (95% CI 31.5 to 39.3) for DD patients, 34.2 months (95% CI 31.0 to 37.6) for ZD patients. Conclusion: A two-year open-label extension treatment phase confirmed the long-term safety profile of denosumab in these breast cancer patients with bone metastases who continued receiving denosumab for up to 5 years or who switched from ZA to denosumab. No new safety signals were observed with up to 5 years of monthly denosumab therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-07.

Combination therapy of lapatinib and Capecitabine for ErbB2-positive metastatic or locally advanced breast cancer: results from the Lapatinib Expanded Access Program (LEAP) in Central and Eastern Europe.

Abstract: Background: The Lapatinib Expanded Access Program (LEAP) was initiated in 45 countries to provide lapatinib in combination with capecitabine to patients with ErbB2 (HER2)-positive breast cancer already treated with anthracyclines, taxanes and trastuzumab We report the results from 12 Central and Eastern European countries Patients and Methods: By 30 September 2008, 293 patients were enrolled Patients were monitored for serious adverse events (SAEs) and for any decrease in left ventricular ejection fraction (LVEF) Overall survival and progression-free survival were also assessed Results: Mean treatment duration was 30 weeks; 107 patients (365%) discontinued therapy during the study, mainly due to disease progression (n = 86; 294%) A total of 78 SAEs were reported from 47 patients; the most frequently reported was diarrhoea (13 reports) Treatment had a relatively small effect on LVEF Decreases were minor (0 to Conclusions: Heavily pretreated patients with ErbB2-positive locally advanced or metastatic breast cancer may benefit from treatment with lapatinib and capecitabine, with a low risk of cardiac toxicity

Preoperative Chemotherapy with Cisplatin and Docetaxel Followed by Surgery and Clip-Oriented Postoperative Chemoradiation in Patients with Localized Gastric or Gastroesophageal Junction Adenocarcinoma: Results from a Phase II Feasibility Study

Abstract: Background We conducted a phase II feasibility study using preoperative chemotherapy with cisplatin and docetaxel followed by surgical resection and postoperative chemoradiation in patients with gastric or gastroesophageal cancer.

Sentinel node biopsy after primary chemotherapy in breast cancer: a note of caution from results of ABCSG-14.

Abstract: n Abstract: Over the past years, experience has been increasing with lymphatic mapping and sentinel node biopsy (SNB) after preoperative chemotherapy for breast cancer, with a wide range of results reported in the literature and final conclusions on the diagnostic value and clinical consequences of this sequential approach still missing. Between 1999 and 2002, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) conducted a prospective randomized multicenter trial comparing three versus six preoperative cycles of epirubicin ⁄docetaxel + granulocyte colony-stimulating factor for operable breast cancer. Of the 292 patients recruited to the trial overall, 111 were enrolled in a prospective subprotocol for performing LM and SNB in addition to obligatory axillary lymph node dissection (ALND) after PC. SNB after PC identified at least one sentinel node in 100 of 111 patients (identification rate 90%). In six cases, a false-negative SN was identified, resulting in a false-negative rate of 13% (6 of 47). We only found little correlation between patients and tumor characteristics and the identification rate or false-negative rate. Lymphatic mapping and SNB after primary chemotherapy failed to predict histologic infiltration of the sentinel node with sufficient sensitivity. The routine use of SNB after primary chemotherapy should therefore be discouraged. n

Brain metastasis-free survival in patients with HER2-positive metastatic breast cancer.

Abstract: 41 Background: Brain metastases (BM) are diagnosed in up to 40% of patients with HER2-positive metastatic breast cancer (MBC). Since the introduction of trastuzumab in 1999, a rising incidence of BM was reported. We aimed to identify factors that prolong BM free survival (BMFS) in all HER2-positive patients (pts) treated for MBC at the Medical University of Vienna from 1999-2009. Methods: BMFS was defined as primary study endpoint and measured as the interval from diagnosis of metastatic disease until diagnosis of brain metastases. 201 pts with HER2-positive MBC were identified from a breast cancer database. 82 pts (40.8%) were diagnosed with BM; 13 pts were excluded from this analysis as brain was the first site of disease progression. Complete data sets of 69 pts with pathologically verified HER2-positive MBC were available. HER2 status was analyzed by immunohistochemistry and reanalyzed by FISH if a score of 2= was gained. BMFS was estimated by using the Kaplan-Meier product-limit method; factors signi...

Opinions on the ASCO 2011 Annual Meeting.

Abstract: survival (OS) was improved for some of these women. There are several issues that urgently need to be addressed: These data are clearly in contrast to the EBCTCG overview for several reasons: There is a 4.3% improvement in distant metastases whereas the local recurrence rate (LRR) benefit was 2.3%. This is against the previous paradigm that at least 10% decrease of LRR needs to be achieved to have a significant shift in OS. Furthermore, the distant metastasis survival curves separate early. In fact, they seem to separate in parallel to the LRR curves. This trial should be considered practice changing. RNI should be considered for patients with higherrisk tumors and 1–3 positive lymph nodes. Among the many interesting reports during the ASCO 2011 I would simply like to point out two other subject areas: 1) Dual inhibition of the Her-2 receptor is a very effective neoadjuvant treatment. It is also striking how effective these treatments are in the absence of cytototoxic treatment. Future research should be directed in defining a subgroup of patients that can be treated without the addition of chemotherapy. This is an exciting direction of clinical research. 2) The German Breast Cancer Group did not receive much attention for a highly interesting abstract concerning the post-neoadjuvant survival of patients (abstract 1028). These data include the survival of over 6,300 women with a median follow-up of 42 months and should be studied with great care, since they are likely to influence many of our treatment and follow-up choices after patients have undergone preoperative chemotherapy.

Effect of change of body mass index (BMI) during therapy on the efficacy of endocrine therapy in premenopausal patients with breast cancer: An analysis of the ABCSG-12 trial.

Abstract: 514 Background: Aromatase inhibitors (AIs) are effective as adjuvant endocrine treatment in breast cancer (BC) patients. Recently, it has been argued that BMI at BC diagnosis impacts on the efficac...

OT2-01-02: First-Line Bevacizumab in Combination with Capecitabine or Paclitaxel for HER2−Negative Locally Recurrent or Metastatic Breast Cancer (LR/MBC): A Randomized Phase III Trial.

Abstract: Background A number of phase III studies have shown significant progression-free survival (PFS) benefits with the combination of bevacizumab (Bev) and either first-line capecitabine (X) or taxane therapy in LR/MBC. The ongoing open-label, randomized, phase III CECOG-sponsored TURANDOT study (CECOG/BC.1.3.005) is investigating the efficacy and safety of first-line Bev plus paclitaxel (P) versus Bev plus X in this setting. Materials and methods: Eligible patients (pts) are aged ≥18 years with HER2−negative, chemonaive LR/MBC, an ECOG performance status of 0–2 and a life expectancy >12 weeks. Prior chemotherapy and concomitant hormonal therapy for LR/MBC are not permitted, but prior (neo)adjuvant chemotherapy is allowed if completed ≥6 months before randomization or ≥12 months if taxane based. Pts are randomized to receive Bev 10mg/kg days 1, 15 plus P 90mg/m2 days 1, 8, 15, q28d (Arm A) or Bev 15mg/kg day 1 plus X 1,000mg/m2 bid days 1–14, q21d (Arm B) until disease progression, unacceptable toxicity or withdrawal of consent. The primary objective is to demonstrate non-inferiority in overall survival (OS) with Bev plus P versus Bev plus X (upper limit ≤1.33 for the two-sided confidence interval for hazard ratio [HR]). Secondary objectives are: comparison of overall response rate (RECIST criteria); PFS; time to response; duration of response; time to treatment failure; safety (CTCAE version 3); and quality of life (EORTC QLQ-30). The recruitment target is 560 pts. A sample size of 490 pts in the per-protocol population will be required to provide 80% power to reject the null hypothesis of inferiority at a one-sided significance level of 0.025, assuming a 24-month median OS with Bev plus P and an alternative hypothesis of HR=1. Data cut-off for adverse event reports was 12 Apr 2010. Interim and final efficacy analyses will be triggered after 175 and 389 events, respectively. Results: Recruitment to the study began in Sep 2008 and was completed in Aug 2010, with 561 pts randomized. Follow-up is ongoing. Conclusions: TURANDOT is the first study to examine the efficacy and safety of Bev plus P versus Bev plus X as first-line treatment for pts with LR/MBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-01-02.

P4-17-05: Brain Metastasis Free Survival (BMFS) Differs between Breast Cancer Subtypes.

Abstract: BACKGROUND Brain metastases (BM) are frequently diagnosed in patients (pts) with Her2-positive metastatic breast cancer (BC); a rising incidence was also reported in triple-negative disease. We hypothesized that pts with triple-negative or Her2-positive tumours had shorter BMFS as compared to other BC subtypes. Therefore, we aimed to compare BMFS in pts with Her2-positive, estrogen receptor (ER) positive and triple-negative BC treated at the Medical University of Vienna from 1999–2009. In Her2-positive tumours, we further investigated the influence of ER co-expression on BMFS, as Her2-positive / ER-positive tumours were reported to express less aggressive biological properties. METHODS BMFS was defined as primary study endpoint and measured as the interval from diagnosis of metastatic BC until diagnosis of BM. A total of 168 pts were identified from a breast cancer database. 34 pts were excluded from this analysis as brain was the first site of disease progression; hence complete datasets from 134 pts were available (69 Her2-positive; 33 triple-negative; 32 ER-positive). Her2 status was analyzed by immunohistochemistry (IHC) and reanalyzed by FISH if a score of 2+ was gained. ER was analyzed by IHC; ER negative tumours were defined by a cut-off value of RESULTS Median BMFS in triple-negative pts was 14 months (m) (95% CI 12.17−15.83), as compared to 25 m (95% CI 13.37−36.62) in Her2-positive (p=0.001) and 35 m (95% CI 19.79−50.22) in ER-positive pts (p In Her2-positive pts, prior trastuzumab treatment for metastatic disease prolonged median BMFS (29 vs. 11 m; p ER-expression (HR 2.03; 95%CI 1.22−3.36; p CONCLUSIONS BMFS in triple-negative disease is significantly shorter as compared to Her2-positive or ER-positive tumours, mirroring the aggressiveness of this breast cancer subtype. Probably due to improved systemic disease control, trastuzumab significantly prolonged BMFS in Her2-positive pts. Longer BMFS in ER/Her2 co-positive disease reflects a less aggressive subtype of Her2-positive breast cancer which is less likely to benefit from strategies of BM screening or prevention. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-05.

Congress Reports · Kongressberichte

Abstract: development and establishment of biomarker assays. Lectures on analytical validity of assays by John Bartlett, UK, and statistical traps by Stefan Michiels, Belgium, concluded this educational session. The next session gave an update on the latest developments of targeted drugs and personalized medicine in oncology. Bryan Hennessy, Ireland, presented an interdisciplinary scientific approach in comparison to the current model of reductionism in cancer research. Lajos Pusztai, USA, talked about the applications of next-generation sequencing of breast cancer genomes and Jorge ReisFilho, UK, followed with a thematically fitting presentation about the opportunities and challenges in massive parallel sequencing. The next day started with a general introduction into cancer immunology. Guiseppe Curigliano, Italy, presented an overview of immunotherapy and how to design an innovative trial giving an example of HER2 immuno-targeted therapy. Laurence Zitvogel, France, then gave an impressive lecture on the role of the immune system in chemoresistance and the synergies between chemotherapy and immunotherapy. Circulating tumor markers were the topic of the next session. Klaus Pantel from Hamburg, Germany, spoke about the potential benefit of circulating tumor cells (CTSs) as prognostic marker and for real-time therapy monitoring. Additionally, Libero Santarpia, Italy, talked about circulating micro RNAs as novel biomarkers for breast cancer. After each session the auditorium took the opportunity to discuss the controversies directly with the faculty members. Moreover, the training course offered a unique platform to network in a small group setting during the breaks enabling an easy dialogue between leaders in the field and the next generation of researchers. In summary, this training course provided a comprehensive review of ongoing breast cancer research and was an excellent preparation for the main conference by bridging the gap between fundamental research and clinical implications. The 3rd IMPAKT Breast Cancer Conference and the preIMPAKT training course, organized by the Breast International Group (BIG) and European Society for Medical Oncology (ESMO), were held on May 4–7, 2011 in Brussels, Belgium. Nearly 600 researchers and oncologists from all over the world attended this annual conference on translational and clinical breast cancer research. This year, the meeting focused on clinically challenging breast cancer subtypes, genomic profiling, tumor microenvironment, preoperative therapies as well as the practical implementation of targeted therapies.