General Session Abstracts最新文献

{"title":"Abstract GS5-06: No survival benefit of chemotherapy escalation in patients with pCR and “high-immune” triple-negative early breast cancer in the neoadjuvant WSG-ADAPT-TN trial","authors":"O. Gluz, U. Nitz, C. Liedtke, A. Prat, M. Christgen, F. Feuerhake, M. Garke, E. Grischke, H. Forstbauer, M. Braun, M. Warm, J. Hackmann, C. Uleer, B. Aktas, C. Schumacher, S. Kuemmel, E. Pelz, Daniel Gebauer, L. Paré, R. Kates, R. Wuerstlein, H. Kreipe, N. Harbeck","doi":"10.1158/1538-7445.SABCS18-GS5-06","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS5-06","url":null,"abstract":"Background:Immune markers such as tumor infiltrating lymphocytes (TILs), CD8, PDL1, PD1 and other protein or mRNA-based genomic markers have been identified as prognostic / predictive in TNBC regarding survival / chemotherapy (CTx) efficacy. In the adjuvant WSG-PlanB trial, patients with high TILs and/or CD8 by mRNA had excellent outcome, irrespective of anthracycline use; in the neoadjuvant ADAPT-TN trial, high PDL1, PD1 and CD8 and/or TILs were predictive for pCR. Still, optimal markers for potential treatment de-escalation have yet to be determined. Here, we analyse for the first time impact of immune mRNA-based markers and TIL9s as prognostic and predictive survival markers. Methods: TNBC patients (ER/PR Results: Present translational analysis included 306 of 336 TNBC patients (36 months median FU). pCR was associated with significantly better survival (3y EFS: 92% vs. 71%, p Bivariate Spearman correlations among CD8, PD1, and PDL1 were strongly positive; their correlations with TILs were moderately positive. Preliminary Cox analysis of EFS was performed with clinical variables (cN, cT, menopausal status); neoadjuvant study arm; pCR; TILs; proliferation markers (baseline Ki67 by IHC, scores derived from PAM50); baseline immune markers; risk scores; and individual gene expression scores previously identified as prognostic for pCR in one or both neoadjuvant arms. Independent prognostic factors included pCR, cN, Ki67, PD1, and CD8; these were entered into (prognostic) interaction analysis. The resulting model contained cN, high Ki67 and low TILs as (unfavorable) main effects and the interaction of (higher) PD1*pCR (favorable). Among pCR patients, the groups with/without additional adjuvant CTX were similar with respect to explanatory factors. Baseline TILs, Ki67, cN, and PD1 were entered into exploratory predictive analysis; the model retained only the interaction [adjuvant CTx * (fractionally ranked) PD1]. In patients with pCR, those with low PD1 benefited from standard anthracycline-containing adjuvant CTx, whereas patients high PD1 did not with an 98% 3y-EFS. Conclusions: Our exploratory results suggest independent prognostic impact of mRNA markers and TIL9s in early TNBC. Patients with both pCR (after 12 weeks) and “high-immune” signature (defined here by PD1) had excellent 3y-EFS and may be candidates for treatment de-escalation (e.g. omission of anthracyclines), whereas “low-immune” pCR patients may benefit from standard adjuvant poly-chemotherapy. Citation Format: Gluz O, Nitz U, Liedtke C, Prat A, Christgen M, Feuerhake F, Garke M, Grischke E-M, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Kuemmel S, Pelz E, Gebauer D, Pare L, Kates R, Wuerstlein R, Kreipe HH, Harbeck N. No survival benefit of chemotherapy escalation in patients with pCR and “high-immune” triple-negative early breast cancer in the neoadjuvant WSG-ADAPT-TN trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84447995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS4-01: Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023)","authors":"E. Rutgers, M. Donker, C. Poncet, M. Straver, P. Meijnen, C. V. D. Velde, R. Mansel, C. Blanken, L. Orzalesi, J. Klinkenbijl, H. V. D. Mijle, S. Veltkamp, M. Riet, M. Albregts, A. Marinelli, H. Rijna, R. T. Morales, M. Snoj, N. Bundred, M. Chauvet, J. Merkus, P. Petignat, D. A. Schinagl, C. Coens, A. Peric, J. Bogaerts, G. Tienhoven","doi":"10.1158/1538-7445.SABCS18-GS4-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS4-01","url":null,"abstract":"Background: Sentinel node biopsy (SNB) is standard in assessing axillary lymph node status in patients with clinically node-negative breast cancer. The 5-year analysis of AMAROS trial showed that if locoregional treatment is advised after a tumor-positive axillary SNB, axillary radiotherapy (ART) is a reasonable alternative for an axillary lymph node dissection (ALND) with less side effects, though follow up was relatively short. Here we present the 10-year follow up data. Methods: From February 2001 to April 2010, patients with primary breast cancer stage cT1-2N0M0 were enrolled in the EORTC phase III non-inferiority AMAROS trial by 34 European sites. Patients were randomized between ALND and ART in case of a tumor-positive SNB. The primary endpoint, axillary recurrence rate (AxR) is now assessed at 10 years in the ITT population using Fine and Gray cumulative incidence method with deaths as competing risks, as well as secondary endpoints: overall survival (OS), distant metastasis free survival (DMFS), second primaries (including cancers other than breast cancers and contralateral DCIS) and locoregional recurrences (LRR). Little extra information beyond 5 years was available concerning Quality of Life and morbidity. Data collection is still ongoing and will be presented later. Results:Of the 4806 patients entered, 1425 patients had a tumor-positive SNB: 744 in the ALND-arm and 681 in the ART-arm, 60% with a macrometastasis. Both treatment-arms achieved a median 10-year follow-up and were comparable regarding age, tumor size, grade, tumor type and adjuvant systemic treatment. In the group who had ALND, the 5-year AxR was 0.41% (95%CI: 0.00;0.88) (4/744) and the 10-year AxR was 0.93% (95%CI:0.18;1.68) (7/744). In the group who had ART, the 5-year AxR was 1.04% (95%CI: 0.27;1.81) (7/681) and the 10-year AxR was 1.82% (95%CI: 0.74;2.94) (11/681) (HR 1.71, 95%CI: 0.67;4.39, p = 0.37). Sensitivity analysis, considering deaths and distant recurrences as competing risks, revealed consistent results. There were no significant differences between treatment arms regarding OS (ALND: 84.6% (95%CI: 81.5;87.1), ART: 81.4% (95%CI: 77.9;84.4), HR 1.17, 95%CI: 0.89;1.52, p= 0.26) and DMFS (ALND: 81.7% (95%CI: 78.5;84.4), ART: 78.2% (95%CI: 74.6;81.3), HR 1.18, 95%CI: 0.92;1.50, p=0.19). Cumulative incidence estimates of 10-year LRR are 3.59% (95%CI: 2.12;5.06) (ALND) versus 4.07% (95%CI: 2.49;5.65) (ART) (p= 0.69). More second primaries were observed after ART: 75/681 (21 contralateral breast) as compared to ALND: 57/744 (11 contralateral breast) (p = 0.035). All results are consistent in the per protocol analysis of patients with a tumor-positive SNB. Conclusion: Axillary recurrence after 10 years in patients with a tumor-positive SNB who were treated with ART is extremely rare and not significantly different from patients who were treated with ALND. OS, DMFS and locoregional control are also comparable. Second primaries including contralateral breast cancers ar","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87087480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS2-03: Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage: Individual patient-level meta-analyses of over 27,000 patients","authors":"Laura M. Spring, G. Fell, A. Arfè, L. Trippa, R. Greenup, K. Reynolds, Barbara L. Smith, B. Moy, S. Isakoff, G. Parmigiani, A. Bardia","doi":"10.1158/1538-7445.SABCS18-GS2-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS2-03","url":null,"abstract":"Background: While the prognostic significance of pathological complete response (pCR) after neoadjuvant chemotherapy is relatively well established, the impact of adjuvant therapy in modulating relationship between pCR and long term outcomes is less clear. The primary objective of this study was to conduct a systematic review of published neoadjuvant chemotherapy studies to comprehensively evaluate the association between pCR with subsequent breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage. Methods: Based on PRISMA guidelines, a search of PubMed from inception until September 2016 was performed to identify eligible studies. Inclusion criteria were clinical trials or studies featuring neoadjuvant chemotherapy that reported pCR results as well as recurrence and/or survival. Hazard Ratios (HRs) and 95% probability intervals (PI) were estimated for endpoints using hierarchical models. We obtained the individual patient-level data for statistical analysis using plot digitizer software. Hazard ratios (HRs), with 95% PIs, measuring the association between pCR and OS or recurrence, were estimated using Bayesian piecewise-exponential proportional hazards hierarchical models including pCR as a predictor. Random effects model was utilized to account for between-study variability in baseline hazards and the variability of the pCR effect between studies. P-value of 0.05 was considered statistically significant. Results: A total of 3,209 citations with associated abstracts were reviewed, and 27,895 patients from 52 studies met inclusion criteria. Attainment of pCR, as compared to absence of pCR, was associated with significantly reduced disease recurrence overall (HR 0.31, 95% PI: 0.24-0.39), and in triple negative (HR 0.18, 95% PI: 0.10-0.31), human epidermal growth factor 2-positive (HER2+) (HR 0.32, 95% PI: 0.21-0.47), and trended towards significance for HR+ breast cancer (HR 0.15, 95% PI: 0.02-1.10). Similarly, pCR after neoadjuvant chemotherapy was also associated with reduced mortality overall (HR 0.22, 95% PI: 0.15-0.30), and among all three major disease subtypes. The association of pCR with reduced recurrence was similar among studies where patients received subsequent adjuvant chemotherapy (HR 0.34, 95% PI: 0.18-0.61) and those without adjuvant chemotherapy (95% HR 0.36, PI: 0.27-0.54). The association between magnitude of pCR change and corresponding change in survival will be presented at the meeting. Conclusion: Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved disease recurrence and survival, particularly for triple negative and HER2+ breast cancer. The similar outcomes with/without adjuvant chemotherapy in patients who attain pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be abbreviated in certain circumstances, and highlights the need for further research to evaluate clinica","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73069795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS3-03: Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: An EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women","authors":"R. Gray","doi":"10.1158/1538-7445.SABCS18-GS3-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS3-03","url":null,"abstract":"Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: an EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women Background: Five years of endocrine therapy with tamoxifen and/or an aromatase inhibitor is highly effective in reducing the risk of recurrence but a substantial risk remains after treatment discontinuation. Continuing treatment with an aromatase inhibitor may mitigate this risk. Methods: We sought individual patient data for meta-analysis from 12 randomised trials that compared 3-5 years of aromatase inhibitor versus no further treatment after five or more years of endocrine therapy. Primary outcomes were recurrence, and breast cancer mortality. Predefined subgroup comparisons were or prior endocrine therapy (tamoxifen alone, tamoxifen then AI, AI alone), site of recurrence (distant, local, contralateral), age, nodal status, tumour size, grade, and period of follow-up (yrs 0-1, 2-5, 5-9, 10+). Five trials randomised 2-3 years prior to treatment divergence and the primary analyses included only women who were recurrence and second primary cancer free and still alive at the point of treatment divergence. Results: Data have so far been received on 7,488 women (100% of those randomised) in trials of extended AI following tamoxifen alone, 10,796 women (82% 0f 13,192 randomised) following prior tamoxifen then AI, and 959 (23% of 4,229 randomised) following AI alone. Preliminary analyses including 1,617 breast cancer recurrences and 854 breast cancer deaths confirm a 35% reduction in recurrence with extended AI following tamoxifen alone but suggest a more moderate reduction after prior AI therapy. Data from two trials (NSABP B-42 & N-SAS BC 05) contributing ˜5666 women should be available before SABCS to allow definitive analyses. Conclusion: This meta-analysis will provide the most reliable possible summary of the available evidence to inform clinicians on the efficacy of extending AI therapy compared to stopping AI after about 5 years of endocrine therapy in preventing disease recurrence and death from breast cancer, both overall and in different categories of women. Citation Format: Gray R, Early Breast Cancer Trialists9 Collaborative Group. Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: An EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-03.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77930929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS3-07: Clinical utility of circulating tumor cell count as a tool to chose between first line hormone therapy and chemotherapy for ER+ HER2- metastatic breast cancer: Results of the phase III STIC CTC trial","authors":"F. Bidard, W. Jacot, S. Dureau, E. Brain, T. Bachelot, H. Bourgeois, A. Gonçalves, S. Ladoire, H. Naman, F. Dalenc, J. Gligorov, M. Espié, C. Lévy, J. Ferrero, D. Loirat, P. Cottu, V. Diéras, C. Simondi, F. Berger, C. Alix-Panabières, J. Pierga","doi":"10.1158/1538-7445.SABCS18-GS3-07","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS3-07","url":null,"abstract":"Background: In ER+ HER2- metastatic breast cancer (MBC) patients, the clinical choice between 1st line hormone therapy (HT, the recommended option) or chemotherapy (CT) is based on the absence of “visceral crisis” or adverse prognostic factors, with no proven/objective criteria. In that context, STIC CTC (NCT01710605) was set up as a strategy trial to test whether circulating tumor cells (CTC) count could help customize the choice between 1st line HT or CT. Methods: For this multicenter phase 3 non-inferiority trial, the main inclusion criteria were: ER+ HER2- MBC with no prior therapy, PS≤2, no contra-indication to HT or CT and informed consent. The a priori treatment choice (HT or CT) and CTC count (CellSearch®) were obtained in all patients prior to randomization. Patients were randomized 1:1 between clinically-driven choice (CTC count not disclosed, HT or CT administered as decided a priori), or a CTC-driven choice (HT if Results: 761 MBC patients were randomized between 02/2012 and 08/2016. Baseline characteristics: 7.8% of patients had a PS=2, 24.1% had a de novo metastatic disease; 63.3% received prior adjuvant HT and 49.9% prior adjuvant CT; 31.3% had ≥3 metastatic sites. A priori treatments (HT or CT) and CTC count ( Conclusion: This trial demonstrates the clinical utility of CTC count as an objective decision tool when considering 1st line therapy in ER+ HER2- MBC. In most patients, CTC count did confirm the a priori clinical choice; however, trial results show that in discrepant cases, CTC count may be trusted for either escalating (i.e. considering CT in patients if high CTC count) or de-escalating (i.e. considering HT in patients if low CTC count) 1st line therapy. Funding: French National Cancer Institute; Menarini Silicon Biosystems. Citation Format: Bidard F-C, Jacot W, Dureau S, Brain E, Bachelot T, Bourgeois H, Goncalves A, Ladoire S, Naman H, Dalenc F, Gligorov J, Espie M, Levy C, Ferrero J-M, Loirat D, Cottu P, Dieras V, Simondi C, Berger F, Alix-Panabieres C, Pierga J-Y. Clinical utility of circulating tumor cell count as a tool to chose between first line hormone therapy and chemotherapy for ER+ HER2- metastatic breast cancer: Results of the phase III STIC CTC trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-07.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"115 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86205631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS4-05: Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial (CRUK/06/003)","authors":"C. Coles, C. Griffin, A. Kirby, J. Haviland, J. Titley, K. Benstead, A. Brunt, C. Chan, L. Ciurlionis, O. Din, E. Donovan, D. Eaton, A. Harnett, P. Hopwood, M. Jefford, P. Jenkins, CE. Lee, M. McCormack, L. Sherwin, I. Syndikus, Y. Tsang, N. Twyman, R. Ventikaraman, S. Wickers, M. Wilcox, J. Bliss, J. Yarnold","doi":"10.1158/1538-7445.SABCS18-GS4-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS4-05","url":null,"abstract":"Background IMPORT HIGH is a randomised, multi-centre phase III trial testing dose escalated simultaneous integrated boost (SIB) against sequential boost each delivered by intensity modulated radiotherapy (IMRT) for early stage breast cancer with higher risk of local relapse. The primary endpoint was initially breast induration at 3 years, requiring 840 patients; accrual was extended (target 2568) with the new primary endpoint of local relapse. We report adverse effects (AE) at 3 years. Methods Women age ≥18 after breast conservation surgery for pT1-3 pN0-pN3a M0 invasive carcinoma were eligible. Randomisation was 1:1:1 between 40Gy/15F to whole breast (WB) + 16Gy/8F sequential photon boost to tumour bed (40+16Gy), 36Gy/15F to WB, 40Gy to partial breast + 48Gy (48Gy) or + 53Gy (53Gy) in 15F SIB to tumour bed. AEs were assessed annually by clinicians in all patients and in a planned sub-set (840) of patients by photographs at 3 years and by patients at 6 months, 1 and 3 years. AE scores were dichotomised as none/mild vs marked for photographs and none/mild vs moderate/marked for patients and clinicians. Fisher9s exact tests compared groups; principal comparison (protocol-specified) between 53Gy and 48Gy (p Results 2617 women consented between 03/2009 and 09/2015 from 39 UK radiotherapy centres. Median follow-up was 49.1 (IQR 36.8-63.2) months. Median age was 49 (IQR 44-56); 9%, 38% & 53% were tumour grade 1, 2 & 3 respectively; 30% were node positive. 66% received chemotherapy and 73% endocrine therapy. 3-year AE data were available for 2017 clinician assessments, 641 photographs and 842 patient assessments. Proportions of patients with marked AEs were low overall. Rates of moderate/marked AEs at 3 years were broadly similar between the randomised groups; with a suggestion of a slightly increased risk for breast induration in 53Gy compared with control (borderline significance). Conclusions These results represent the largest and most mature reported AE outcomes of breast SIB within a clinical trial. At 3 years, rates of moderate/marked AEs were similar between SIB IMRT and WB + sequential boost IMRT delivered over 3 and 4.5 weeks respectively. Citation Format: Coles CE, Griffin CL, Kirby AM, Haviland JS, Titley JC, Benstead K, Brunt AM, Chan C, Ciurlionis L, Din OS, Donovan EM, Eaton DJ, Harnett AN, Hopwood P, Jefford ML, Jenkins PJ, Lee CE, McCormack M, Sherwin L, Syndikus I, Tsang Y, Twyman NI, Ventikaraman R, Wickers S, Wilcox MH, Bliss JM, Yarnold JR. Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial (CRUK/06/003) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-05.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90673643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS1-10: Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE","authors":"C. Geyer, C. Huang, Mano, S. Loibl, E. Mamounas, M. Untch, N. Wolmark, P. Rastogi, H. Fischer, A. Redondo, C. Jackisch, W. Jacot, A. Conlin, A. Schneeweiss, I. Wapnir, P. Fasching, M. DiGiovanna, P. Wuelfing, C. Arce‐Salinas, J. Crown, Z. Shao, E. R. Caremoli, Haiyan Wu, L. H. Lam, D. Tesarowski, M. Smitt, Hannah Douthwaite, S. Singel, G. Minckwitz","doi":"10.1158/1538-7445.SABCS18-GS1-10","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS1-10","url":null,"abstract":"Background: Patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy have a high risk of recurrence and death. The current standard of care is continuation of the same HER2-targeted therapy in the adjuvant setting for one year. T-DM1 has shown activity and a favorable benefit-risk profile in metastatic patients with disease progression after prior chemotherapy plus HER2-targeted therapy. Thus, T-DM1 may also be active in patients with residual invasive disease after neoadjuvant HER2-targeted therapy. Methods: KATHERINE (NCT01772472/BO27938/NSABP B-50-I/GBG 77) is a phase III, open-label, global study of patients with centrally confirmed HER2-positive (IHC3+ or ISH+) primary breast cancer (T1–4, N0–3, M0) who received neoadjuvant chemotherapy plus HER2-targeted therapy, which had to include a taxane and trastuzumab, followed by surgery, with pathologically documented residual invasive disease in the breast and/or axillary lymph nodes. Within 12 weeks of surgery, patients were randomized 1:1 to T-DM1 (3.6 mg/kg IV q3w) or trastuzumab (6 mg/kg IV q3w), for 14 cycles. Randomization was stratified by clinical stage at presentation, hormone receptor status, single versus dual neoadjuvant HER2-targeted therapy, and pathological nodal status after neoadjuvant therapy. Patients received radiotherapy and/or endocrine therapy per local standards. The primary endpoint is invasive disease-free survival (IDFS). A single interim analysis (IA) was planned after approximately 67% of the IDFS events required for the primary analysis had occurred, with an efficacy stopping boundary of HR?0.732 or p Results: After review of the pre-specified IA, the IDMC recommended full analysis and disclosure of the results. With 256 IDFS events reported, administration of T-DM1 significantly improved IDFS compared with trastuzumab (unstratified HR=0.50; 95% CI: 0.39 to 0.64; p Conclusions: Adjuvant T-DM1 substantially improved IDFS in patients with HER2-positive early breast cancer with residual disease after completion of neoadjuvant therapy. Citation Format: Geyer, Jr. CE, Huang C-S, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Fischer HH, Redondo A, Jackisch C, Jacot W, Conlin AK, Schneeweiss A, Wapnir IL, Fasching PA, DiGiovanna MP, Wuelfing P, Arce-Salinas C, Crown JP, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, von Minckwitz G. Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-10.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86584443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS2-02: Efficacy and utilization trends of adjuvant chemotherapy for stage I, II, and III breast cancer in the elderly population: A National Cancer Database (NCDB) analysis","authors":"S. Sinha, L. Panebianco, X. Wu, Dongliang Wang, Danning Huang, A. Sivapiragasam","doi":"10.1158/1538-7445.SABCS18-GS2-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS2-02","url":null,"abstract":"Background: The role of adjuvant chemotherapy in early stage breast cancer is well established with survival benefit seen in long term follow up studies, but only a small minority of patients in these studies were >65 years old. Dose and schedule can be tailored according to the special requirements of an elderly patient, as stated by the International Society of Geriatric Oncology (SIOG). However the magnitude of the benefit and trends in utilization of adjuvant chemotherapy has not been well studied in this population. Methods: Female patients above 65 years age with stage I to III breast cancer were identified from the NCDB database from 2004-2015. Factors predicting utility of chemotherapy were assessed with multivariate analysis. Kaplan Meier curves were constructed for calculation of overall survival (OS) with hazard ratio (HR) estimated from cox model. Log rank test and pearson chi square was used for comparison between groups. Groups were compared for OS benefit at 5 and 10 years. Results: Of a total of 2,445,730 patients analyzed, 160,676 met our inclusion criteria. Of them, 21,743 were >80 years old. Factors predicting use of adjuvant chemotherapy were shown in table 1. OS benefit was seen in patients who received adjuvant chemotherapy regardless of their age, ER, PR, HER-2 status or stage. Patients with TNBC had an HR of 0.547. More benefit was seen in the higher stages. HR for stages I, II, and III were 0.801, 0.608, and 0.666 respectively. Conclusions: Adjuvant chemotherapy is considered standard of care for patients with early stage breast cancer. Elderly patients are more likely to get adjuvant chemotherapy based on histology, age Citation Format: Sinha S, Panebianco L, Wu X, Wang D, Huang D, Sivapiragasam A. Efficacy and utilization trends of adjuvant chemotherapy for stage I, II, and III breast cancer in the elderly population: A National Cancer Database (NCDB) analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-02.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"124 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87838033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS2-04: Efficacy results from CIBOMA/2004-01_GEICAM/2003-11 study: A randomized phase III trial assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer","authors":"M. Martín, C. Barrios, L. Torrecillas, M. Ruiz-Borrego, J. Bines, J. Segalla, A. Ruíz, J. García-Saenz, R. Torres, J. Haba, E. García, H. Gómez, A. Llombart, M. Borbolla, J. Baena, A. Barnadas, Luis Calvo, L. Pérez-Michel, M. Ramos, J. Castellanos, Á. Rodríguez-Lescure, J. Cárdenas, J. Vinholes, E. M. Dueñas, M. J. Godes, M. Seguí, A. Antón, P. López-Álvarez, J. Moncayo, G. Amorim, E. Villar, S. Reyes, C. Sampaio, B. Cardemil, M. Escudero, S. Bezares, E. Carrasco, A. Lluch","doi":"10.1158/1538-7445.SABCS18-GS2-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS2-04","url":null,"abstract":"Background: Triple negative breast cancers (TNBC) have a greater risk of relapse than non-TNBC. New therapeutic approaches are needed for these patients (pts). CIBOMA/2004-01_GEICAM/2003-11 is a multinational, randomized phase III trial exploring adjuvant capecitabine (X) after completion of standard treatment in early TNBC pts. Materials and Methods: Patients with operable, node-positive (or node-negative with tumor size ≥ 1 cm), centrally confirmed hormone receptor-negative, HER2-negative early BC, who had received 6–8 cycles (cy) of standard anthracycline and/or taxane-containing chemotherapy or 4 cy of doxorubicin-cyclophosphamide (for node-negative disease) in the (neo)adjuvant setting, were eligible. Patients were randomized to either 8 cy of X (1,000 mg/m2 bid, days 1–14, every 3 weeks) or observation. Stratification factors included center, prior taxane-based therapy, number of involved axillary lymph nodes and phenotype (basal vs non-basal, according to cytokeratins 5/6 and/or EGFR positivity). The primary objective was to compare the disease-free survival (DFS) between both treatment arms, and secondary objectives included the comparison in terms of 5-year DFS, overall survival (OS) and safety. Assuming a 30% risk reduction in DFS rate at 5 years (from 64.7% to 73.7%, hazard ratio 0.70) with 80% power and a two-tailed log-rank test at 0.05, 834 evaluable pts were needed. 876 pts had to be finally enrolled considering a drop-out rate of 5%. Results: Recruitment of 876 pts from 8 countries was completed in September 2011. Median age was 49 years; 68.5% of pts were postmenopausal, 55.5% were lymph node negative, 71.7% had a basal phenotype, 67.5% received chemotherapy based on anthracyclines and taxanes. Median follow-up was 7.3 years (range 0.0 to 11.1). DFS was not significantly prolonged with X vs observation (hazard ratio (HR) 0.82; 95% confidence interval (CI), 0.63 to 1.06; P=0.1353). Five-year DFS was 79.6% (95% CI, 75.8% to 83.4%) with X and 76.8% (95% CI, 72.7% to 80.9%) with observation. OS was not statistically different between treatment arms (HR 0.92; 95% CI, 0.66 to 1.28; P=0.6228). In subgroup analysis for DFS, we found no statistically significant interaction between X treatment and different subgroups, with the exception of basal vs non-basal phenotypes (basal HR 0.97, 95% CI 0.72 to 1.32, P=0.8620; non-basal HR 0.51, 95% CI, 0.31 to 0.86, P=0.0101; interaction P=0.0357). Similar results were found for OS (basal HR 1.20, 95% CI 0.81 to 1.77, P=0.3684; non-basal HR 0.48, 95% CI, 0.26 to 0.91, P=0.0205; interaction P=0.0155). 75.2% of pts completed 8 cy of X, with a median relative dose intensity of 86.3%. Grade (G) 3 or higher adverse events (AEs) were observed in 40.4% of pts in X arm. In 9.6% of pts the AEs were related with X. Hand-foot syndrome was the most common AE in X arm (G3 on 18.8% of pts). Conclusions: In our study, the addition of adjuvant X after standard (neo) adjuvant anthracycline and/or taxane-containing c","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"154 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75325584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS6-05: The impact of breast cancer surgery on quality of life: Long term results from E5103","authors":"Shoshana M. Rosenberg, A. O'Neill, Karen R. Sepucha, K. Miller, C. Dang, D. Northfelt, G. Sledge, B. Schneider, A. Partridge","doi":"10.1158/1538-7445.SABCS18-GS6-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS6-05","url":null,"abstract":"Background: Breast cancer (BC) treatment, including surgery, can impact not only short-term health outcomes but may also affect longer term health-related and psychosocial quality of life (QOL). We sought to describe the impact of BC surgery on QOL among breast cancer survivors followed in a large randomized trial. Methods: The ECOG-ACRIN protocol E5103 was a phase III trial that randomized BC patients (pts) who had undergone definitive BC surgery to receive adjuvant doxorubicin, cyclophosphamide, and paclitaxel with either bevacizumab (bev) or placebo. Telephone based surveys were administered to all pts enrolled between 01/Jan/10 and 08/Jun/10 as part of a Decision-Making/QOL component until 18 mos post enrollment. Functional/psychosocial QOL domains were assessed by the EQ-5D-3L and the FACT B+G. Fisher9s exact test compared categorical and Wilcoxon rank sum test compared continuous variables between subgroups. Multivariable regression was used to evaluate factors in addition to primary surgery at enrollment (age, race, ER/PgR status, tumor size, nodal status) associated with overall FACT score at 18 mos. Results: Patient reported outcomes at 18 mos were available from 89.6% (465/519) pts. At enrollment, 57% (266/465) had a mastectomy; 43% (199/465) breast conserving surgery (BCS). Median age at enrollment was 52 (range: 25-76) years. There were no differences in QOL between bev vs placebo treatment arms (EQ-5D-3L Index Score p=0.65; FACT B+G Score p=0.23) at 18 mos so groups were combined. Using EQ-5D-3L, over half of the pts (58%) reported at least some pain/discomfort; 38% symptoms of anxiety/depression. A higher proportion of mastectomy pts reported problems with usual activities compared to BCS pts (Table). Compared to BCS pts, mastectomy pts had lower average EQ5D-3L scores 0.80 vs. 0.84, p=0.04 and FACT B+G scores 109 vs. 114, p=0.01, indicating worse QOL. In univariate analyses, non-white race (p=0.03), ER/PgR+ status (p=0.04) and mastectomy as primary surgery (p=0.01) were significantly associated with worse QOL (lower FACT B+G scores). In multivariable analyses, non-white race (p=0.02) and ER/PgR+ status (p=0.05) remained associated with worse QOL; mastectomy was borderline significant (p=0.06). Conclusions: Among women participating in a contemporary adjuvant BC chemotherapy trial, a substantial proportion of survivors experience symptoms that may be amenable to intervention, including referral to physical rehabilitation, especially among pts undergoing more extensive surgery. Attention to psychosocial health is also essential both during and after completion of active treatment to optimize QOL outcomes. Citation Format: Rosenberg SM, O9Neill A, Sepucha K, Miller KD, Dang CT, Northfelt DW, Sledge GW, Schneider BP, Partridge AH. The impact of breast cancer surgery on quality of life: Long term results from E5103 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (P","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78674201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}