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  • 1
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    World Congress Integrative Medicine & Health 2017: Part one : Berlin, Germany. 3-5 May 2017
    Springer Science and Business Media LLC ; 2017
    In:  BMC Complementary and Alternative Medicine Vol. 17, No. S1 ( 2017-6)
    Details
    In: BMC Complementary and Alternative Medicine, Springer Science and Business Media LLC, Vol. 17, No. S1 ( 2017-6)
    Type of Medium: Online Resource
    ISSN: 1472-6882
    URL: Article
    DOI: 10.1186/s12906-017-1782-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
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  • 2
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    Preliminary safety results from a multicenter phase II noncomparative two arm pilot of bevacizumab with anastrozole or fulvestrant as 1st line metastatic breast cancer therapy.
    American Association for Cancer Research (AACR) ; 2009
    In:  Cancer Research Vol. 69, No. 2_Supplement ( 2009-01-15), p. 4113-
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 2_Supplement ( 2009-01-15), p. 4113-
    Abstract: Abstract #4113 Background: Estrogen modulates angiogenesis through effects on endothelial cells and by induction of vascular endothelial growth factor (VEGF) expression. Increased VEGF promotes tumor growth and is associated with a poor response to anti-estrogen therapy. This trial evaluates the impact of bevacizumab (B) combined with anastrozole (A) or fulvestrant (F) on progression free survival (PFS) as first line endocrine therapy in metastatic breast cancer (MBC). & #x2028; Methods: Study design: Two arm nonrandomized, noncomparative trial of A or F in combination with B. Eligibility: 0 prior hormonal or chemotherapy for MBC, measureable or evaluable disease, normal LVEF, postmenopausal, normal organ function. Treatment: Arm 1: Patients (pts) who either were endocrine therapy naïve, ≥ 12 months from adjuvant endocrine therapy, or who had intolerance to or progression on tamoxifen were treated with anastrozole 1 mg po daily. Arm 2: Patients who were ≤ 12 months from adjuvant aromatase inhibitors (AIs), intolerant of or progressed on adjuvant AIs, or at physician's discretion were treated with fulvestrant 500 mg IM loading dose, 250 mg D15 and every q28 days thereafter. B 10 mg/kg q2wks beginning day 1 was administered in both arms. Concurrent trastuzumab (T) was administered in HER2+ patients. Response assessments were performed q8 wks. Pts were treated until disease progression or toxicity. & #x2028; Results: 44 pts have been enrolled with data available for 29 pts. 18 pts (62%) were treated with anastrozole and 11 pts (38%) with fulvestrant. Median age: 64 yrs (range 44-88), ECOG PS 0-17 pts (59%) and PS 1 -12 pts (41%). 7 pts (24%) presented with de novo stage IV disease. 52% had 2 or more metastatic disease sites with bone metastases predominating 16 pts (55%), 7 pts (24%) with bone only disease. There were no G3/4 heme toxicities. G3/4 non-hematologic events consisted of G3 hypertension in 3 pts (10%), arthralgias 1 pt (3%), and CHF 1 pt (3%). This symptomatic LVEF of 40% occurred in arm 1 during cycle 3 and was noted to recover to 50-55% within 1 wk. This pt did not receive T. A median of 4.5 cycles have been administered. PRs were noted in 7 pts (24%) and 14 pts (48%) demonstrated SD. PD was noted in 3 pts and 5 pts were not yet evaluable. 73% of pts are progression free at 12 months. At a median follow up of 7.5 months, median PFS and overall survival has not been reached. & #x2028; Conclusions: The combination of bevacizumab with anastrozole or fulvestrant is feasible and well tolerated with adverse events as expected, reflecting standard bevacizumab related toxicities. Bevacizumab in combination with endocrine therapy is promising with early evidence of a high rate of clinical benefit at 72%. Further follow up is warranted. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4113.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.SABCS-4113
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
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  • 3
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    Abstract GS4-07: Results from a randomized placebo-controlled phase 2 trial evaluating exemestane ± enzalutamide in patients with hormone receptor–positive breast cancer
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 4_Supplement ( 2018-02-15), p. GS4-07-GS4-07
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 4_Supplement ( 2018-02-15), p. GS4-07-GS4-07
    Abstract: Background: The androgen receptor (AR) is expressed in & gt;75% of hormone receptor (HR)+ tumors. AR signaling has been associated with resistance to endocrine therapy (ET). Aromatase inhibitors (AIs) divert estrogen precursors to androgens; in preclinical models enzalutamide (ENZA) blocked both estrogen- and androgen-mediated growth of HR+ cells. In a phase 1 study of ET+ENZA in breast cancer, doubling the dose of exemestane (EXE) to 50 mg was necessary to restore exposure observed with 25 mg.1 Methods: This placebo (PBO)–controlled phase 2 trial randomized patients (pts) with HR+/HER2-normal advanced/metastatic breast cancer (MBC) to either 25 mg EXE+PBO or 50 mg EXE+160 mg ENZA daily (NCT02007512). Two parallel cohorts enrolled pts who had no prior ET (C1) or who had received 1 prior ET for MBC (C2). Randomization was stratified on resistance to prior ET and prior exposure to AI. Tissue samples for biomarker development were mandatory. Brain metastases or a history of seizure was exclusionary. One prior chemotherapy regimen for MBC was permitted. Response was assessed every 8 weeks for 48 weeks, then every 12 weeks. Crossover to ENZA+EXE was allowed at disease progression. A gene signature–based biomarker (Bmkr) indicating AR signaling predictive of response to ENZA was developed using a training set of RNAseq data from 2/3 of randomized pts and validated using a test set of data from the remaining 1/3 of pts. Progression-free survival (PFS) according to RECIST v1.1 was the primary endpoint in the intent-to-treat (ITT) population and in the Bmkr+ subgroup of each cohort. Secondary endpoints included clinical benefit rate at 24 weeks (CBR24), best overall response, and safety. Results: A total of 247 pts were randomized (C1, n=127; C2, n=120). In C1, 50 pts (39.4%) were Bmkr+; in C2, 35 pts (29.2%) were Bmkr+. Statistically significant improvements in median PFS and CBR24 were observed only in the Bmkr+ population with no prior ET (Table). The most common adverse events (AEs) reported in the ENZA+EXE arms were nausea (39%) in C1 and fatigue (37%) in C2. In C1, 9 pts (15%) and 10 pts (16%) discontinued the study due to AEs in the ENZA+EXE and PBO+EXE arms, respectively. In C2, 11 pts (18%) and 5 pts (8%) discontinued due to AEs in the ENZA+EXE and PBO+EXE arms, respectively. Conclusions: In the first reported randomized trial of ENZA in HR+ MBC, ENZA+EXE was well tolerated with no new safety signals. The study met its primary endpoint in pts with Bmkr+ MBC with no prior ET. 1. Schwartzberg et al. Clin Cancer Res. 2017 Mar 9 [Epub ahead of print].  C1: No Prior ETC2: 1 Prior ET ITTBmkr+ITTBmkr+EXE+ENZA | PBOENZA | PBOENZA | PBOENZA | PBO n=63 | n=64n=24 | n=26n=60 | n=60n=15 | n=20Primary endpointPFS, median, months11.8 | 5.816.5 | 4.33.6 | 3.96.0 | 5.3(95% CI)(7.3, 15.9) | (3.5, 10.9)(11.0, NR) | (1.9, 10.9)(1.9, 5.5) | (2.6, 5.4)(2.3, 26.7) | (1.8, 6.7)Hazard ratio0.820.441.020.55(95% CI)(0.54, 1.26)(0.21, 0.96)(0.66, 1.59)(0.23, 1.36)P value0.36310.03350.92120.1936Secondary endpointCBR24, n (%)39 (62) | 29 (45)20 (83) | 10 (38)12 (20) | 19 (32)6 (40) | 6 (30)(95% CI)(49, 74) | (33, 58)(63, 95) | (20, 59)(11, 32) | (20, 45)(16, 68) | (12, 54)P value0.06090.00120.14430.5374 Citation Format: Krop I, Abramson V, Colleoni M, Traina T, Holmes F, Estevez L, Hart L, Awada A, Zamagni C, Morris P, Schwartzberg L, Chan S, Wheatley D, Gucalp A, Biganzoli L, Steinberg J, Gianni L, Trudeau M, Tudor IC, Markova D, Barry E, Tarazi J, Stewart R, Winer E, Yardley DA. Results from a randomized placebo-controlled phase 2 trial evaluating exemestane ± enzalutamide in patients with hormone receptor–positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS4-07.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS17-GS4-07
    RVK:
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    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 4
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    Abstract P1-12-04: A phase 2 study of eribulin in breast cancer not achieving a pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC)
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 4_Supplement ( 2016-02-15), p. P1-12-04-P1-12-04
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 4_Supplement ( 2016-02-15), p. P1-12-04-P1-12-04
    Abstract: Background: Residual breast cancer after NAC is associated with a high risk of recurrence. Little evidence supports the use of further chemotherapy in this setting. Eribulin, an inhibitor of microtubule dynamics, demonstrated a survival advantage in patients with metastatic breast cancer who had progressed after previous anthracycline and taxane therapy. This phase 2 trial assessed the efficacy of eribulin (2-yr disease-free survival) administered postoperatively to breast cancer pts not achieving a pCR following standard NAC. Methods: Women with invasive breast cancer (stage T1-4b, N0-2, M0 at diagnosis) and evidence of residual cancer ( & gt;5 mm) in the breast or axillary lymph nodes (LN) following ≥4 cycles of standard anthracycline and/or taxane-containing NAC were eligible. Additional eligibility criteria: age ≥18 yrs, peripheral neuropathy & lt; 1, adequate hematologic, hepatic, and renal function. 3 groups were studied: Cohort A-triple negative (TN), Cohort B-HR+/HER2-, Cohort C-HER2+. After recovery from definitive surgery, all pts received eribulin mesylate 1.4mg/m2 IV on days 1 and 8 every 21 days for 6 cycles. Cohort C pts also received trastuzumab 6mg/kg IV day 1 every 21 days for a total of 1 yr from start of NAC. Adjuvant hormonal therapy and loco-regional radiotherapy were administered per institutional guidelines. We hypothesized post-operative eribulin would result in a 40% increase over the reported 40% 2 yr DFS for TN, and a 15% increase over the reported 80% 2 yr DFS for HR+/HER2- pts who did not achieve pCR following standard NAC. Results: 127 pts were enrolled (54, Cohort A; 42, Cohort B; 31, Cohort C). Pts on Cohort C continue with study treatment. Here, we present the results of 95 pts treated on Cohorts A and B. Median age-52 yrs (range, 27-74). 87 pts (92%) had invasive ductal adenocarcinoma, 6 (6%) invasive lobular, 1 (1%) mucinous, and 1 (1 %) unknown; 34 pts (36%) had T3 or T4 tumors and 65 (68%) had N1-2 disease at diagnosis. NAC with anthracyclines was administered to 74 pts (78%), taxanes to 88 (93%), and 72 (76%) received both. 71 pts (75%) had mastectomies, 24 (25%) had breast conserving surgery. Median residual tumor was 17.5 mm (range 0.1 to 80); 60 pts (63%) were LN+. 78 pts (81%) completed the planned 6 cycles of eribulin. Adjuvant radiation was administered in 28 pts (30%). 3 pts discontinued treatment due to toxicity (1 each with G3 neutropenia, G3 nausea, and unknown grade neuropathy). The most common treatment-related G3/4 adverse events were neutropenia [29 pts (31%)] and leukopenia [10 pts (11%)] . 3 pts (3%) had G3/4 febrile neutropenia and 2 pts (2%) had G3/4 neuropathy. Growth factors were administered to 22 pts (24%). There were no treatment-related deaths. With a median follow up of 19.2 and 14.9 months for Cohorts A and B respectively, the 2 yr DFS probabilities calculated from date of surgery were 61.1 % (95% CI-41.2-76.0) for Cohort A; 82.2% (95% CI-60.2-92.7) for Cohort B. Conclusions: The addition of eribulin is safe and feasible in pts who do not achieve pCR following anthracycline and/or taxane based NAC. At a median follow up of 19.2 months, a statistically significant improvement in the estimated 2 yr DFS was evident in the TN (Cohort A) pts. Citation Format: Yardley DA, Peacock N, Shroff S, Molthrop, Jr DC, Anz B, Daniel BR, Young RR, Weaver R, Harwin W, Webb CD, Ward P, Shastry M, DeBusk LM, Midha R, Hainsworth JD, Burris III HA. A phase 2 study of eribulin in breast cancer not achieving a pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-04.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS15-P1-12-04
    RVK:
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    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 5
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    Abstract P6-11-03: A phase 2 open-label study of lucitanib in patients (pts) with FGF aberrant metastatic breast cancer (MBC)
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 4_Supplement ( 2017-02-15), p. P6-11-03-P6-11-03
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 4_Supplement ( 2017-02-15), p. P6-11-03-P6-11-03
    Abstract: BACKGROUND: Lucitanib is a potent, oral antiangiogenic tyrosine kinase inhibitor of Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3), Platelet-Derived Growth Factor Receptors alpha and beta (PDGFRα/β), and Fibroblast Growth Factor Receptors 1-3 (FGFR1-3). FGF aberrancies (amplification of FGFR1,or 11q[amplicon containing FGF ligands 3, 4, and 19]), are genomic alterations observed in over 20% of breast cancer pts and promote cancer proliferation and survival. METHODS: MBC pts who had received at least 1 metastatic line of therapy were randomized 1:1 to 10 or 15 mg QD of lucitanib. Stratification was based on local assessment of FGF aberrancy; pts with both FGFR1 and 11q-amplified tumors were stratified as FGFR1 amplified. Central confirmation of FGFR1 or 11q amplification was done using Abbott FISH probes (FGFR1 or 11q copy number ≥ 6 and a ratio of FGFR1 or 11q to centromere ≥ 2). Investigator-assessed progression-free survival (PFS) was the primary endpoint. Secondary endpoints included objective response rate (ORR) per RECIST 1.1, disease control rate (DCR), duration of response (DR), and incidence of treatment-emergent adverse events (TEAE). RESULTS: Enrollment completed in 3/2016; 178 pts that received at least 1 dose of lucitanib are included in this analysis (baseline characteristics in Table 1). Due to grade 3 hypertension in the 15 mg group (46% vs 37% in 10 mg group), enrollment to the 15 mg group was halted. Overall, most pts (97%) experienced at least 1 TEAE, with the most frequently (≥ 30%) occurring events being hypertension (73%), fatigue (48%), nausea (43%), hypothyroidism (40%), and headache (33%). Grade ≥ 3 TEAEs occurred in 66% of pts, with hypertension as the most frequent event (40%) followed by proteinuria and hyponatremia (both 6%). AEs were manageable with dose interruption or reduction, with approximately 8% of pts ending treatment due to an AE. Current median PFS is 3.5 mos (95% CI 2.8-4.6; range 0.62-12.95) and 2.6 mos (95% CI 1.8-2.9; range 0.82-18.87) respectively for the 10 mg and 15 mg treatment groups. No differences in clinical activity were observed by treatment group, FGF aberrancy, hormone receptor or HER2 status. Of the 168 evaluable pts, confirmed ORR was 3%; overall DCR was 27% (32% for pts in the 10 mg group compared to 20% for the 15 mg group); overall mean (standard deviation) DR of 3.3 (1.8) mos. Baseline Characteristics 10 mg QD15 mg QD N=109N=69Age (years)Median5653Range27-8227-80SexFemale109 (100%)67 (97%)Male02 (3%)ECOG PSmissing5 (5%)2 (3%)051 (47%)30 (43%)153 (49%)37 (54%)Number of prior anticancer therapies in the metastatic setting & gt; 332 (29%)21 (30%)3-648 (44%)32 (46%) & gt; 629 (27%)16 (23%)Endocrine/HER2 statusmissing7 (6%)1 (1%)ER+ or PR+74 (68%)50 (73%)HER2+12 (11%)7 (10%)TNBC16 (15%)11 (16%)FGFR aberrancyFGFR1 amplified54 (49%)29 (42%)11q amplified31 (28%)24 (35%)FGFR1 and 11q amplified13 (12%)9 (13%)FGFR1 and 11q non-amplified11 (10%)7 (10%) CONCLUSION: At 10 mg QD, lucitanib has modest activity with manageable toxicity in this heavily pretreated pt population. Future clinical development for lucitanib may focus on alternative biomarkers to identify sensitive tumors and rational combinations with other anti-cancer drugs. Citation Format: Mayer IA, Arteaga CL, Nanda R, Miller KD, Jhaveri K, Brufsky AM, Rugo H, Yardley DA, Vahdat LT, Sadeghi S, Audeh MW, Rolfe L, Litten J, Knox A, Raponi M, Tankersley C, Isaacson J, Wride K, Morganstern DE, Vogel C, Connolly RM, Gradishar WJ, Patel R, Pusztai L, Abu-Khalaf M. A phase 2 open-label study of lucitanib in patients (pts) with FGF aberrant metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS16-P6-11-03
    RVK:
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    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 6
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    Abstract OT2-01-05: TRINITI-1: Ribociclib + everolimus (EVE) + exemestane (EXE) triplet combination in men or postmenopausal women with HR+, HER2– advanced breast cancer (ABC) following progression on a cyclin-dependent kinase (CDK) 4/6 inhibitor
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 4_Supplement ( 2017-02-15), p. OT2-01-05-OT2-01-05
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 4_Supplement ( 2017-02-15), p. OT2-01-05-OT2-01-05
    Abstract: Background: There is extensive crosstalk between the cyclin D–CDK4/6–inhibitor of CDK4–retinoblastoma and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways at the G1/S cell-cycle checkpoint. Both pathways are frequently dysregulated in hormone receptor-positive (HR+) breast cancer and have been associated with endocrine therapy (ET) resistance. CDK4/6 and PI3K/mTOR inhibitors have demonstrated clinical activity in combination with ET. Although CDK4/6 inhibitors combined with ET significantly improve progression-free survival (PFS) in ABC, disease progression eventually occurs, highlighting the need for effective treatment options following doublet therapy. Ribociclib (LEE011; CDK4/6 inhibitor; 3-weeks-on/1-week-off) + EVE (mTOR inhibitor) + EXE triplet therapy has shown preliminary clinical activity in heavily pretreated HR+, human epidermal growth factor receptor 2-negative (HER2–) ABC including patients (pts) with prior exposure to CDK4/6 inhibitors, suggesting this combination may restore sensitivity to CDK4/6 inhibitor-based therapy. Trial design and objectives: TRINITI-1 (NCT02732119) is a US-based, phase I/II, single arm, open-label study of ribociclib (continuous daily dosing) + EVE (2.5 mg/day) + EXE (25 mg/day) in men and postmenopausal women with HR+, HER2– ABC refractory to ≥1 line of ET. Phase I dose escalation consists of 2 ribociclib dose-level cohorts (250 and 300 mg/day), followed by a Simon Two-Stage phase II trial in pts with disease progression on prior CDK4/6 inhibitor-based therapy. No more than 3 lines of therapy for ABC, including ≤1 prior chemotherapy regimen, are permitted. Previous EXE treatment of & gt;28 days for metastatic disease, prior mTOR inhibitors, and progression on & gt;1 CDK4/6 inhibitor are prohibited. All pts in phase II must have progressed on a CDK4/6 inhibitor as the last regimen before study entry. Additional eligibility criteria include measurable disease or lytic/mixed bone lesions and Eastern Cooperative Oncology Group performance status of ≤1. Exclusion criteria include visceral crisis, unstable CNS metastases, and clinically significant heart disease. Phase I primary objective: maximum tolerated dose and/or recommended phase II dose of the triplet combination. Phase II primary objective: clinical benefit rate (CBR) at 24 weeks (0.1 significance level, 80% power to test CBR ≤15% against CBR ≥30%) with centrally-assessed PFS as a key secondary objective. Other secondary objectives include preliminary antitumor activity (phase I), safety and pharmacokinetics (phase I/II), and overall response rate, overall survival, and duration of overall response (phase II). Tumor assessments (RECIST v1.1) will be performed every 8 weeks for the first 12 months, and every 12 weeks thereafter until disease progression. Exploratory analyses include biomarkers potentially predictive of response and mechanisms of resistance. Target accrual: Approximately 52 pts at ∼30 sites; 3–6 pts per cohort in phase I, an initial 19 in phase II with another 20 enrolled upon demonstration of clinical benefit in ≥4 pts. Citation Format: Bardia A, Hurvitz S, Yardley DA, Zelnak A, DeMichele A, Clark AS, Warsi G, Small T, Tucci C, Moulder S. TRINITI-1: Ribociclib + everolimus (EVE) + exemestane (EXE) triplet combination in men or postmenopausal women with HR+, HER2– advanced breast cancer (ABC) following progression on a cyclin-dependent kinase (CDK) 4/6 inhibitor [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-05.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS16-OT2-01-05
    RVK:
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    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 7
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    Abstract P5-08-08: Baseline (BL) characteristics, treatment (tx) patterns, and outcomes in patients with hormone receptor (HR)+ vs HR– HER2+ disease from the SystHERs registry
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 4_Supplement ( 2017-02-15), p. P5-08-08-P5-08-08
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 4_Supplement ( 2017-02-15), p. P5-08-08-P5-08-08
    Abstract: Introduction HR+ metastatic breast cancer (MBC) generally has a more indolent course than HR– MBC. Less is known about differences in BL characteristics and disease outcomes by HR status in HER2+ MBC in the modern tx setting where patients (pts) may recur after adjuvant therapy. SystHERs is an ongoing, prospective, observational cohort study of HER2+ MBC pts. Here we describe BL characteristics, tx patterns, and outcomes by HR status and MBC diagnosis type. Methods SystHERs enrolled pts aged ≥18 years and within 6 months of MBC diagnosis. Locally-determined HR status was captured at initial diagnosis and/or disease recurrence; HR+ was defined as ER+ and/or PR+ disease in primary (early BC) or MBC. Tx data are shown for pts ≥9 months from MBC diagnosis to capture the completion of chemotherapy and the addition of hormonal therapy during maintenance tx. Median overall survival (OS; Kaplan-Meier) and the hazard ratio (Cox regression) were estimated. Results As of Feb 2016, data were available for 872 eligible pts with known HR status; 70% had HR+ disease and 50% had de novo MBC. Median follow-up from MBC diagnosis was 16.5 months (range, 0.4–49.4 months). Clinically important BL demographics and disease characteristics with noticeable differences are presented in Table 1. More black (vs white) pts were observed to be HR–. More recurrent (vs de novo) pts were observed to be HR+. MBC tx choices may be influenced by adjuvant tx. Table 2 shows the most common first-line tx regimens in de novo vs recurrent pts with HR+ HER2+ disease and ≥9 months from MBC diagnosis. Among these pts, 60% de novo and 56% recurrent pts received any hormonal therapy. The most common first-line tx regimen for pts with HR– disease was chemotherapy + HER2-targeted therapy (92%). There were 88 (15%) and 55 (21%) deaths in the HR+ and HR– groups, respectively. Median OS was not reached for either group, but the hazard ratio favored pts with HR+ disease (log-rank P=0.026; hazard ratio 0.683; 95% CI 0.488–0.957). Table 1. BL characteristics HR+ HER2+ (n=608)HR– HER2+ (n=264)Race, %  White8272Black1321MBC diagnosis type, %  De novo4758Recurrent*5342Visceral disease, %6375No significant differences in other characteristics by HR status (eg, sex, ethnicity, education, menopausal status, performance status, number of metastatic sites at diagnosis). *Pts with prior adjuvant therapy: HR+, 89%; HR–, 83%. Table 2. Most common first-line tx regimens in pts with HR+ HER2+ disease and ≥9 months from MBC diagnosis De novo (n=227)Recurrent (n=235)Chemotherapy + HER2-targeted therapy + hormonal therapy, %4938Chemotherapy + HER2-targeted therapy only, %3741HER2-targeted + hormonal therapy only, %1014 Conclusions In SystHERs, 70% of pts with HER2+ MBC had HR+ disease. A higher percentage of recurrent pts had HR+ disease vs de novo pts, perhaps suggesting selective elimination of HR– clones during adjuvant tx. While black pts are known to be more likely to develop HR– HER2– BC, our results show that HR– HER2+ disease is also more common in black pts, suggesting a proclivity for this population to develop HR– MBC regardless of HER2 status. In these early results, survival was higher in pts with HR+ HER2+ MBC. Citation Format: Cobleigh M, Yardley DA, Brufsky A, Rugo H, Swain S, Kaufman PA, Tripathy D, Mayer M, Hurvitz S, O'Shaughnessy J, Mason G, Chu L, Antao V, Beattie M, Yoo B, Jahanzeb M. Baseline (BL) characteristics, treatment (tx) patterns, and outcomes in patients with hormone receptor (HR)+ vs HR– HER2+ disease from the SystHERs registry [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-08.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS16-P5-08-08
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    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 8
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    Abstract P6-18-15: Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety analysis
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 4_Supplement ( 2019-02-15), p. P6-18-15-P6-18-15
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 4_Supplement ( 2019-02-15), p. P6-18-15-P6-18-15
    Abstract: Background: In Phase III trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + various endocrine therapy (ET) partners has demonstrated significantly prolonged progression-free survival vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we further evaluate the safety of RIB-based regimens of interest for the proposed indication (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL] ) using pooled data from three Phase III trials (MONALEESA [ML]-2 [NCT01958021] , -3 [NCT02422615], and -7 [NCT02278120] ). Methods: Postmenopausal pts with HR+, HER2– ABC received RIB (600 mg/day; 3-weeks-on/1-week-off) or PBO + letrozole (LET; 2.5 mg/day; ML-2 [no prior ET for ABC]) or FUL (500 mg, Days 1 and 15 of Cycle 1, then Day 1 of every cycle thereafter; ML-3; no or ≤1 prior line of ET for ABC] ). Premenopausal pts (ML-7; no prior ET and ≤1 chemotherapy for ABC]) received RIB or PBO + anastrozole (1 mg/day)/LET (2.5 mg/day) + goserelin (3.6 mg every 28 days). Adverse events (AEs) were characterized per Common Terminology Criteria for Adverse Events v4.03; safety analyses included time to first event, duration of event, and rate of associated RIB/PBO discontinuations. Results: Data for 1883 pts were pooled; 1065 pts received RIB + ET and 818 pts received PBO + ET (median exposure to study treatment: 17 and 13 months, respectively). Exposure-adjusted incidence rates for AEs of special interest were 561 and 131 per 100 pt-years in the RIB and PBO arms, respectively. The most common all-causality Grade 3/4 AEs (≥10% in any arm; RIB vs PBO) were neutropenia (59% vs 2%), leukopenia (18% vs 1%), and hypertension (13% vs 13%). A new Fridericia's corrected QT interval (QTcF) & gt;480 ms occurred in (n/N) 52/1054 (5%) vs 11/814 (1%) pts in the RIB vs PBO arms; a new QTcF & gt;500 ms occurred in 14/1054 (1%) vs 1/814 ( & lt;1%) pts. Median time to first event for Grade ≥2 neutropenia, elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), and QTc prolongation in the RIB arm was 2, 12, and 2 weeks, respectively; median duration of first Grade ≥2 event was 4, 4, and 2 weeks. In the RIB arm vs PBO arms, 7% vs 3% of pts discontinued study treatment due to AEs; common all-grade AEs leading to RIB/PBO discontinuation (≥2% in any arm) were elevated ALT (4% vs & lt;1%) and elevated AST (2% vs 1%). Discontinuation due to QT prolongation occurred in 4 pts in the RIB arm and 2 in the PBO arm (both & lt;1%). All-grade serious AEs occurred in 25% of pts in the RIB arm vs 15% of pts in the PBO arm. Conclusions: RIB in combination with various ET partners continues to demonstrate a predictable and manageable tolerability profile across a broad population of pts with HR+, HER2– ABC. Citation Format: Burris HA, Chan A, Im S-A, Chia S, Tripathy D, Esteva FJ, Campone M, Bardia A, Kong O, Bao W, Diaz-Padilla I, Rodriguez Lorenc K, Yardley DA. Ribociclib + endocrine therapy in hormone receptor-positive, HER2-negative advanced breast cancer: A pooled safety 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 P6-18-15.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS18-P6-18-15
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 9
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    Abstract P1-14-06: A phase II randomized study with eribulin/cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in HER2-negative breast cancer- Final analysis of primary endpoint and correlative analysis results
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 4_Supplement ( 2016-02-15), p. P1-14-06-P1-14-06
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 4_Supplement ( 2016-02-15), p. P1-14-06-P1-14-06
    Abstract: Background: Eribulin mesylate (Er) is a non-taxane inhibitor of microtubule growth that results in G2-M cell cycle arrest, disruption of normal mitotic spindles and apoptosis. Er demonstrated an overall survival (OS) but not progression free survival (PFS) advantage in anthracycline and taxane refractory breast cancer pts. This OS rather than PFS benefit has been attributed to Er's potential to suppress new metastases through its effects on the epithelial mesenchymal transition (EMT) pathway, even in the absence of an effect on the primary tumor or established metastases. In this study ErC was compared to TC, a standard regimen for (neo) adjuvant treatment. A companion exploratory analysis examined the EMT markers E-cadherin and vimentin, as well as the endothelial marker CD-31 assessing tumor vasculature. Final assessments of the primary endpoint of pathological complete response (pCR) and results of the correlative studies will be presented. Methods: Women with histologically confirmed invasive HER2-negative (IHC 0-1+ or FISH/SISH negative), cT1-3, cN0-2, M0 (pN3a disease allowed) adenocarcinoma of the breast were eligible. Following a 10 pt lead-in to confirm the safety/feasibility of ErC, pts were randomized 2:1. Arm 1, Er 1.4 mg/m2 IV (Days 1 & 8) and C 600 mg/m2 IV (Day 1); Arm 2, T 75 mg/m2 IV and C 600 mg/m2 IV on Day 1, both regimens administered q 21 days x 6 cycles followed by surgery. Tumor samples were collected at baseline and from residual breast cancer at the time of surgery. Samples were assayed for E-cadherin, vimentin, and CD-31 expression by immunohistochemistry. Results: Enrollment was completed 4/2014 (76 pts); 10 pts in lead-in phase, 66 pts were randomized (Arm 1, 44; Arm 2, 22). In the randomized population, 77% had invasive ductal adenocarcinoma; median tumor size 3.1 cm (range, 0.4-10cm; 29.5% were T3); axillary nodes clinically positive in 52%. 34% of pts were triple negative (TN). 59 pts (89%) underwent surgery after receiving neoadjuvant chemotherapy (NAC) on study. pCR rates were 9% and 18% on the TC and ErC arms respectively. 4/7 pts with pCR on the ErC arm were TN. tumor samples were analyzed from 69 pts (including lead-in pts) for expression of the EMT biomarkers. Of these, 40 pts had paired pre- and post-treatment samples, and 29 pts had either a pre- or post-treatment sample (including 8 pre-treatment samples from pts who achieved pCR). In pre-treatment tumor specimens (61 samples), E-cadherin levels were modest-high in 80%, vimentin expression was seen in 39%, and CD-31 expression observed in 21% of the samples. Analysis of pre- and post-treatment paired specimens and differential effects according to treatment regimen will be presented. Conclusion: The observed pCR rate of 18% with ErC in this HER2- pt population was comparable with other NAC regimens. Correlative evaluation of EMT markers and tumor vascular density with response is ongoing and will be presented. Citation Format: Yardley DA, Chandra P, Hart L, Wright GS, Ward P, Mani A, Shastry M, Finney L, Guo S, DeBusk LM, Hainsworth JD, Burris III HA. A phase II randomized study with eribulin/cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in HER2-negative breast cancer- Final analysis of primary endpoint and correlative analysis results. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-06.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS15-P1-14-06
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 10
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    Abstract P5-09-04: Consensus and disagreement between experts and community practitioners asked to make therapeutic recommendations for early breast cancer (EBC)
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 4_Supplement ( 2016-02-15), p. P5-09-04-P5-09-04
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 4_Supplement ( 2016-02-15), p. P5-09-04-P5-09-04
    Abstract: Intro. Most patients with stage II BC will receive surgery along with systemic therapy, but no consensus exists among experts on optimal use of neoadjuvant vs adjuvant therapy in many cases. Furthermore, treatment guidelines list multiple reasonable regimens for EBC, but lack patient-specific recommendations. We have shown previously that online decision support tools can affect treatment decisions of community practitioners. In this study, we sought to determine areas of consensus and disagreement among expert faculty providing treatment recommendations for a 2015 decision support tool on EBC as well as those using the online tool. Methods. An online decision support tool was developed with input from 5 experts on systemic therapy recommendations for 235 patient scenarios in EBC. Tool users were asked to enter specific patient criteria and their intended management for each case before displaying the 5 expert recommendations for the user-entered case. Users were asked to indicate if the expert recommendations changed their intended approach. Results. At interim analysis, 406 individuals used this tool, with 674 patient scenarios entered. Among users reporting on the tool's clinical impact, 88% indicated expert recommendations either confirmed or changed their intended therapy. Expert recommendations in the tool showed areas of consensus and disagreement in treating patients with EBC. For example, expert recommendations varied in the choice of systemic therapy prior to surgery and when to continue directly to surgery before systemic treatment. Expert recommendations for initiating systemic neoadjuvant therapy in HER2-, HR+ EBCcNcTExpert 1Expert 2Expert 3Expert 4Expert 5NCCN GuidelinesNegativecT1a       cT1b       cT1c    Recommend  cT2 RecommendConsider cT3ConsiderRecommendConsiderPositivecT1a   RecommendConsider cT1b   RecommendConsider cT1c   RecommendConsider cT2ConsiderRecommendConsider cT3ConsiderRecommendConsider Experts did agree on starting with surgery in patients with node-negative, T1a disease; however, only 30% of tool users agreed. Both experts and users agreed in recommending systemic neoadjuvant therapy for patients with HER2+, node-positive T2 disease. In patients with HER2+ EBC, experts always chose to include dual HER2-targeted therapy in neoadjuvant systemic therapy but only included trastuzumab in adjuvant regimens. However, only 51% of tool users selected dual HER2-targeted therapy as part of neoadjuvant therapy and 13% use dual HER2-targeted therapy in the adjuvant setting. Expert opinion varied on when to use adjuvant chemotherapy in patients with HR+, HER2- EBC, particularly for those with intermediate or unknown recurrence scores and no lymph node involvement. Detailed comparison of expert consensus and disagreement, analysis of practice pattern information from user responses, and perceived impact of the expert recommendations will be presented. Conclusions. This EBC tool highlights specific clinical scenarios having either consensus or disagreement among experts and community practitioners. Education that includes online decision support tools may increase the number of clinicians making optimal treatment decisions for patients with EBC. Citation Format: Obholz KL, Rosenthal KM, O'Regan RM, Swain SM, Yardley DA, Brady ED. Consensus and disagreement between experts and community practitioners asked to make therapeutic recommendations for early breast cancer (EBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-09-04.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS15-P5-09-04
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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    detail.hit.zdb_id: 1432-1
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