A equipe do MOC selecionou os abstracts de maior impacto da ASCO 2014. Veja abaixo os destaques em Câncer de mama:

HER2+

• A multicenter randomized study comparing 6 versus 12 months of trastuzumab in combination with dose-dense docetaxel following FEC as adjuvant treatment of women with axillary node-positive or high-risk, node-negative breast cancer overexpressing HER2
• Differential effects of metformin on breast cancer proliferation according to insulin resistance and tumor subtype in a presurgical trial
• Efficacy of adjuvant trastuzumab (T) compared with no T for patients (pts) with HER2-positive breast cancer and tumors ≤ 2cm: A meta-analysis of the randomized trastuzumab trials
• First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC)
• T-DM1 in HER2-positive breast cancer brain metastases (BM)
• AVATAXHER: An open-label, randomized, multicenter study investigating the addition of bevacizumab (B) to neoadjuvant trastuzumab (T) plus docetaxel (D) in patients with early stage HER2-positive breast cancer (HER2+ BC) stratified according to PET change after one therapy cycle

RH +

• Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance)
• Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials
• Bevacizumab (Bv) in the adjuvant treatment of HER2-negative breast cancer: Final results from Eastern Cooperative Oncology Group E5103
• Bevacizumab plus paclitaxel optimization study with interventional maintenance endocrine therapy in advanced or metastatic ER-positive HER2-negative breast cancer: JBCRG-M04 (BOOSTER) trial
• Arobase: A phase III trial of exemestane (Exe) and bevacizumab (BEV) as maintenance therapy in patients (pts) with metastatic breast cancer (MBC) treated in first line with paclitaxel (P) and BEV – A Gineco study
• ARTemis: A randomised trial of bevacizumab with neoadjuvant chemotherapy (NACT) for patients with HER2-negative early breast cancer – Primary endpoint, pathological complete response (pCR)
•  Does chemotherapy schedule matter when combining with bevacizumab? A stratified meta-analysis of randomized controlled trials
• German Adjuvant Intergroup Node Positive (GAIN) study: A phase III trial to compare IDD-ETC versus EC-TX in patients with node-positive primary breast cancer – Final efficacy analysis

Mama – Triplo negativo

• Efficacy of neoadjuvant carboplatin/docetaxel chemotherapy in sporadic and BRCA-associated triple-negative breast cancer (TNBC)
• Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): Results from GeparSixto
• Randomized phase II study of weekly paclitaxel with or without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA HER2-negative breast cancer
• TBCRC028: A phase Ib/II trial of GDC-0941 (a PI3K inhibitor) in combination with cisplatin in metastatic androgen receptor-negative triple-negative breast cancer (TNBC)
• Triple-negative breast cancer subtypes and pathologic complete-response rate to neoadjuvant chemotherapy: Results from the GEICAM/2006-2003 study

HER2+

A multicenter randomized study comparing 6 versus 12 months of trastuzumab in combination with dose-dense docetaxel following FEC as adjuvant treatment of women with axillary node-positive or high-risk, node-negative breast cancer overexpressing HER2

Abstract No: 623
Type: General Poster Session
Time: Monday June 2, 8:00 AM to 11:45 AM
Location: S Hall A2
Author(s): Dimitrios Mavroudis, Nikolaos A. Malamos, Stylianos Kakolyris, et al.
Axillary node positive or high risk node negative women with HER2 overexpressing or amplified early breast cancer were randomized following surgery to receive either 6 (arm A) or 12 (arm B) months of adjuvant trastuzumab in combination with dose dense G-CSF-supported Docetaxel (75mg/m² every 14 days for 4 cycles) following FEC (5FU 700mg/m², epirubicin 75mg/m², Conclusions: Preliminary results of this study in terms of disease relapse and DFS are in favor of 12 months of adjuvant trastuzumab administration. Clinical trial information: NCT00615602.

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Differential effects of metformin on breast cancer proliferation according to insulin resistance and tumor subtype in a presurgical trial

Abstract No: 599
Type: General Poster Session
Time: Monday June 2, 8:00 AM to 11:45 AM
Location: S Hall A2
Author(s): Andrea De Censi, Matteo Lazzeroni, Valentina Aristarco, et al.
200 non-diabetics were randomly allocated to either metformin (850 mg/bid) or placebo for 4 weeks prior to breast cancer surgery. Response was assessed by comparing baseline biopsy (Ki-67 and tumor subtype) and serum markers (HOMA, C-peptide, IGF-I, IGFBP-1, IGFBP-3, hsC-reactive protein, adiponectin) with the same measurements at surgery. For patients with a blood sample taken <24 hours from last drug intake, metformin level was measured. Conclusions: At antidiabetic doses, the effect of metformin on tumor Ki-67 of nondiabetic breast cancer patients is modest and varies with host and tumor characteristics. These findings are relevant to clinical trials of metformin in breast cancer prevention and treatment. Clinical trial information: ISRCTN16493703.

Median (IQR) Ki-67 changes (post-pre treatment) by arm and biomarker threshold

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Efficacy of adjuvant trastuzumab (T) compared with no T for patients (pts) with HER2-positive breast cancer and tumors ≤ 2cm: A meta-analysis of the randomized trastuzumab trials

Abstract No: 508
Type: Oral Abstract Session
Time: Saturday May 31, 3:00 PM to 6:00 PM
Location: N Hall B1
Author(s): Ciara Catherine Maria O’Sullivan, Ian Bradbury, Evandro De Azambuja, et al.
Six randomized controlled trials (RCT) were identified by a Medline search from 2004-2013. Trial groups from 5 phase III RCTs provided data (HERA, NCCTG N9831, NSABP B31, PACS 04, and FinHER).In total, 11,200 pts were randomized in these 5 trials;4,220 of whom had ≤2cm tumors, and known number of positive axillary lymph nodes and HR status(2,588 randomized to T and 1,632 to no T). The individual pt meta-analysis will include pts with tumors ≤2 cm (T1a, T1b and T1c) and 0-1, 2-3 and ≥ 4 positive lymph nodes. Separate analyses will be performed for the two HR cohorts. This analysis will complement the published summary data-based Cochrane Review (Moja et al. 2012) by allowing a detailed investigation of the effect of disease characteristics, such as HR, on treatment effects. In addition to the standard Yusuf-Peto fixed effects model (Yusuf et al. 1985) we will investigate the impact of heterogeneity in study baseline hazards and study treatment effects by fitting random effect models.An intention to treat approach will produce a conservative effect estimate as substantial numbers of control-group pts ‘crossed over’ to the T arm after positive DFS results were reported. Methods to account for this ‘selective crossover’ are being developed; we plan to extend these methods to the meta-analysis setting to provide less conservative estimates. Results: Pending. Conclusions: A meta-analysis of 5 randomized adjuvant T trials focusing on pts with tumors ≤2cm will be performed and results submitted before the meeting.

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First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC)

Category: Breast Cancer – HER2/ER
Abstract No: LBA4
Type: Plenary Session
Time: Sunday June 1, 1:00 PM to 4:00 PM
Location: N Hall B1
Author(s): Martine J. Piccart-Gebhart, Andrew Peter Holmes, Jose Baselga, et al.
Abstract:
The full, final text of this abstract will be posted online at 7:30 AM (EDT) on Sunday, June 1.

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T-DM1 in HER2-positive breast cancer brain metastases (BM)

Abstract No: 650
Type: General Poster Session
Time: Monday June 2, 8:00 AM to 11:45 AM
Location: S Hall A2
Author(s): Rupert Bartsch, Anna Sophie Berghoff, Margareta Rudas, et al.
A total of six consecutive pts (median age 55 years) with Her2-positive breast cancer and BM were treated with T-DM1. In two asymptomatic pts, T-DM1 was administered as primary systemic therapy, while four subjects had already received local therapy and had documented CNS progression. T-DM1 was administered intravenously at a dose of 3.6 mg/kg body weight every three weeks; re-assessment of disease status was performed every three cycles. At baseline and restaging, MRI was performed. CNS response was defined as a reduction of lesion size of ≥50%. Conclusions: This prospective case series again indicates that systemic therapy offers activity in Her2-positive BM. Currently, LapCap remains the standard of care. Still, T-DM1 offers relevant clinical activity; therefore, the role of T-DM1 in BM should be investigated in larger studies.

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AVATAXHER: An open-label, randomized, multicenter study investigating the addition of bevacizumab (B) to neoadjuvant trastuzumab (T) plus docetaxel (D) in patients with early stage HER2-positive breast cancer (HER2+ BC) stratified according to PET change after one therapy cycle

Abstract No: 507
Type: Oral Abstract Session
Time: Saturday May 31, 3:00 PM to 6:00 PM
Location: N Hall B1
Author(s): Bruno P. Coudert, Jean-Yves Pierga, Marie-Ange Mouret-Reynier, et al.
Patients were ≥18 yrs old with stage T2/3, N0/1 HER2+ BC. Patients received two 3-weekly cycles of T (8 mg/kg, then 6 mg/kg) and D (100 mg/m²). Those with ≥70% ΔSUV in PET values between cycle 1 and 2 received four more cycles of T+D, one cycle of T, then surgery (standard arm). Those with <70% ΔSUV were randomized 2:1 to four cycles of T+D+B (15 mg/kg; arm a) or T+D (arm b), then one T cycle and surgery. The primary endpoint was pCR rate at surgery. The positive (PPV) and negative predictive value (NPV) of ΔSUV on pCR rate and safety were also investigated. Conclusions: Adding B to neoadjuvant T+D, in tumors with a low likelihood of pCR predicted by PET ΔSUV, increased the pCR rate from 24.0% to 42.5%. PET ΔSUV, by selecting low responding HER2+ tumors, may be a useful tool for optimizing neoadjuvant therapy for HER2+ BC. Clinical trial information: 2009-013410-26.

RH +

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Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance)

Abstract No: LBA505
Type: Oral Abstract Session
Time: Saturday May 31, 3:00 PM to 6:00 PM
Location: N Hall B1
Author(s): Halle C. F. Moore, Joseph M. Unger, Kelly-Anne Phillips, et al.
Abstract: The full, final text of this abstract will be posted online at 2:00 PM (EDT) on Friday, May 30.

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Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials

Abstract No: LBA1
Session: Plenary Session Including the Science of Oncology Award and Lecture
Type: Plenary Session
Time: Sunday June 1, 1:00 PM to 4:00 PM
Location: N Hall B1
Author(s): Olivia Pagani, Meredith M. Regan, Barbara Walley, et al.
Abstract: The full, final text of this abstract will be posted online at 7:30 AM (EDT) on Sunday, June 1.

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Bevacizumab (Bv) in the adjuvant treatment of HER2-negative breast cancer: Final results from Eastern Cooperative Oncology Group E5103

Abstract No: 500
Session: Breast Cancer – HER2/ER
Type: Oral Abstract Session
Time: Saturday May 31, 3:00 PM to 6:00 PM
Author(s): Kathy Miller, Anne M. O’Neill, Chau T. Dang, et al.
Pts were assigned 1:2:2 to one of three treatment arms. In addition to doxorubicin and cyclophosphamide followed by wkly paclitaxel, pts received either placebo (Arm A – AC>T), Bv during chemo (Arm B – BvAC>BvT), or Bv during chemo -> Bv monotherapy for 10 cycles (Arm C – BvAC>BvT>Bv). Randomization was stratified and Bv dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with Bv in Arm C. The primary endpoint was invasive disease free survival (IDFS) requiring 426 IDFS events across Arms C and A to detect hazard ratio (HR) of 0.75 with 80% power using a one-sided 2.5% (two-sided 5%) stratified log rank test. uncommon and similar among all arms (3/4/4% respectively) but Bv exposure was less than anticipated with ~24% of pts in Arm B and ~55% of pts in Arm C discontinuing Bv before completing planned therapy. With a median follow-up of 47.5 mos. and 430 IDFS events across Arms C and A, 5-yr IDFS (95%CI) was 77%(70.9%-81.2%/76%(71.5%-79.8%)/80%(77%-82.5%) respectively. Conclusions: Incorporation of Bv into anthracycline and taxane containing adjuvant therapy does not improve IDFS or OS in pts with high risk HER2- breast cancer. Bv did increase AEs but no unexpected AEs were encountered. Longer duration therapy is unlikely to be feasible given the high rate of early discontinuation due to all causes. Clinical trial information: NCT00433511.

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Bevacizumab plus paclitaxel optimization study with interventional maintenance endocrine therapy in advanced or metastatic ER-positive HER2-negative breast cancer: JBCRG-M04 (BOOSTER) trial

Meeting: 2014 ASCO Annual Meeting
Abstract No: TPS657
Type: General Poster Session
Time: Monday June 2, 8:00 AM to 11:45 AM
Location: S Hall A2
Author(s): Shigehira Saji, Masakazu Toi, Takashi Ishikawa, et al.
Background: In the standard management of inoperable or recurrent breast cancer (BC), active therapy is continued until disease progression (PD) or unacceptable toxicity. In patients (pts) receiving first-line bevacizumab (BV) plus paclitaxel (PTX), this strategy results in some pts discontinuing treatment because of PTX-related peripheral sensory neuropathy despite sustained tumor response. To overcome this problem, we propose a practical treatment strategy in pts with ER-positive HER2-negative BC, introducing temporary BV + endocrine maintenance therapy in pts responding to BV + PTX followed by BV + PTX reintroduction at first PD. This strategy may reduce the impact of peripheral sensory neuropathy, enable pts to maintain their quality of life (QOL) and prolong disease control. Methods: JBCRG-M04 (BOOSTER; UMIN000012179; ClinicalTrials.gov NCT01989780) is a multicenter open-label randomized phase II trial in pts with ER-positive HER2-negative inoperable or recurrent BC. After 16–24 weeks of induction therapy with BV 10 mg/kg q2w + PTX 90 mg/m² days 1, 8 and 15 q4w, pts achieving a complete or partial response or stable disease (investigator assessed) are randomized to either A: continued BV + PTX; or B: a switch to maintenance BV + endocrine therapy, followed by BV + PTX at the time of either PD or clinical PD on maintenance therapy. Tumor tissue, DNA and sequential plasma samples are collected before and during treatment for biomarker research. The primary endpoint is time to failure of strategy (TFS), defined as the interval between randomization and either PD on study therapy, change to new agent not in study regimen, first PD not followed by BV + PTX in arm B, or death. The planned sample size of 160 pts provides 80% power to detect a 6-month increase in TFS in arm B versus arm A. Secondary endpoints include overall survival, 2-year survival rate, progression-free survival, safety and QOL. Biomarker analyses include correlations between biomarkers and response, changes in angiogenesis regulators and comparison of biomarker levels between initial and reintroduced BV + PTX. Clinical trial information: NCT01989780.

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Arobase: A phase III trial of exemestane (Exe) and bevacizumab (BEV) as maintenance therapy in patients (pts) with metastatic breast cancer (MBC) treated in first line with paclitaxel (P) and BEV – A Gineco study

Category: Breast Cancer – HER2/ER
Meeting: 2014 ASCO Annual Meeting
Abstract No: 501
Type: Oral Abstract Session
Time: Saturday May 31, 3:00 PM to 6:00 PM
Location: N Hall B1
Author(s): Olivier Tredan, Philippe Follana, Isabelle Moullet, et al.
In this prospective, randomized, open label, phase III study, pts with histologically confirmed ER+ HER2- locally advanced or MBC, who had not progressed after 16-24 weeks of 1st-line P+BEV therapy, were randomized to P+BEV continuation vs ET+BEV (Exe 25 mg/d+BEV 15 mg/kg q3w). Primary endpoint was PFS. To demonstrate an improvement in the 6-month PFS rate (PFS-6m) from 50% with P+BEV to 65% with ET+BEV (2-sided α=5%) with 80% power, 141 events were requiered and 198 pts were planned. An interim analysis (IA) was planned after 40% of required events. Secondary endpoints included overall survival (OS) and toxicity. Conclusions: The efficacy hypothesis was not reached, despite a better safety profile of the ET+BEV maintenance therapy. Exploratory analyses are planned to identify potential subgroups benefiting from it. Clinical trial information: NCT01303679.

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ARTemis: A randomised trial of bevacizumab with neoadjuvant chemotherapy (NACT) for patients with HER2-negative early breast cancer – Primary endpoint, pathological complete response (pCR)

Abstract No: 1014
Type: Poster Highlights Session
Time 1: Monday June 2, 1:15 PM to 4:15 PM
Author(s): Helena Margaret Earl, Louise Hiller, Clare Blenkinsop, et al.
ARTemis is a randomised phase 3 trial adding bev to NACT (docetaxel (D)-FEC). Pts with HER2-neg invasive breast cancer were eligible. Stratification was by age, ER status (neg: weak pos: strong pos), tumour size (T2:T3/4), clinical involvement of axillary nodes and inflammatory/locally advanced disease. Pts were randomised (1:1) to bev+D-FEC or D-FEC. The primary endpoint was pCR, defined as no residual invasive cancer in the breast or axillary lymph nodes after NACT. 800 pts were required to detect 10% differences in pCR rates, at the 5% (2-sided) level of significance with 85% power. Conclusions: ARTemis showed a significant improvement in pCR with the addition of bev to D-FEC. ER-neg and ER-weak pos / HER2-neg breast cancer pts appeared to benefit most from bev, whilst pCR rates in ER-strong pos pts were lower and did not appear to show improvement from the addition of bev. Our results are similar to those reported in Geparquinto and CALGB 40603. Clinical trial information: 68502941.

* p-value across treatment groups, after adjusting for ER.

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 Does chemotherapy schedule matter when combining with bevacizumab? A stratified meta-analysis of randomized controlled trials

Abstract No: 1076
Type: General Poster Session
Time: Monday June 2, 8:00 AM to 11:45 AM
Location: S Hall A2
Author(s): Twan Ying Chang, Yaa Hui Dong, Ching-Hung Lin, et al.
Through literature search, we identified 26 RCTs which compared combination of Bev plus CT with CT alone for advanced cancers. Among them, 21 RCTs which contained different CT schedules within certain cancer type were enrolled. These included 5, 4, 5 and 7 RCTs for breast, ovary, lung and colorectal cancers. A meta-analysis with random effects model was conducted to generate summary estimates of Bev benefit in terms of the improvement of PFS. CT schedules were classified into weekly (w), non-weekly (non-w), and weekly + non-weekly (w/non-w). We performed the stratified analysis of CT schedules, CT drugs, and CT lines, cancer types, and Bev dosage/schedule. The Bucher’s method was used to indirectly compare the PFS improvement from Bev. Conclusions: When combining Bev with CT, weekly CT schedule was associated with greater improvement of PFS.

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German Adjuvant Intergroup Node Positive (GAIN) study: A phase III trial to compare IDD-ETC versus EC-TX in patients with node-positive primary breast cancer – Final efficacy analysis

Abstract No: 1009
Type: Poster Highlights Session
Time 1: Monday June 2, 1:15 PM to 4:15 PM
Location 1: E354b
Author(s): Volker Jochen Moebus, Gunter Von Minckwitz, Christian Jackisch, et al.
Pts were randomized to idd-ETC (E:150 mg/m², T:225 mg/m², C:2500-2000 mg/m², i.v. day 1, q15 for 3 cycles each) or EC followed by T plus capecitabine (X) (EC-TX) (E: 112.5 mg/m² + C: 600 mg/m², i.v. day 1, q 15 for 4 cycles followed by T: 67.5 mg/m² i.v. day 1, q 8 for 10 weeks + X: 2000 mg/m² p.o. day 1-14, q 22 for 4 cycles). After recruitment of 1,500 patients the dose of C was reduced to 2000 mg/m². Pts aged 18-65 years with involved axillary LN were eligible. 3000 pts with 801 events were needed to show an increase of 5-year DFS (primary endpoint) from 75% to 79% for patients receiving EC→TX after 8 years total study duration. Conclusions: Both dose-dense regimens achieved a highly favorable 5-year DFS superior to our assumptions mainly based on the preceeding idd-ETC study. The addition of a fourth cytostatic drug (here capecitabine) did not improve efficacy of dose-dense therapy, but led to higher toxicity. Clinical trial information: NCT 001 968 72.

MAMA – Triplo negativo

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Efficacy of neoadjuvant carboplatin/docetaxel chemotherapy in sporadic and BRCA-associated triple-negative breast cancer (TNBC)

Sub-category: Triple-Negative Breast Cancer
Abstract No: 1022
Attend this session at the 2014 ASCO Annual Meeting
Type: Poster Highlights Session
Time 1: Monday June 2, 1:15 PM to 4:15 PM
Location 1: E354b
Author(s): Priyanka Sharma, Shane R. Stecklein, et al.
205 patients with stage I (T>1cm) II or III TNBC were enrolled in a prospective multisite registry between 2011-2013, out of which 42 patients received neoadjuvant chemotherapy regimen of Carboplatin AUC 6 + Docetaxel 75 mg/m²every 21 D (4-6 cycles). Following neoadjuvant therapy, all patients underwent breast surgery. pCR (no evidence of invasive tumor in the breast and axilla) and Residual Cancer Burden(RCB) was evaluated. RCB of 0 or1 was designated as near pCR (pCRn). All patients underwent comprehensive BRACAnalysis (Myriad). Conclusions: We report very encouraging near pathologic response in both sporadic (68%) and BRCA-associated (86%)TNBC with a neoadjuvant platinum/taxane chemotherapy regimen. This Carboplatin/Docetaxel combination yielded pCR rates similar to observed rates with A/C plus Carboplatin however, is devoid of potential cardiac and secondary leukemia side effects and should be explored further in randomized studies.

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Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (gBRCA) mutation and triple-negative breast cancer (TNBC): Results from GeparSixto

Abstract No: 1005
Type: Oral Abstract Session
Time: Tuesday June 3, 9:45 AM to 12:45 PM
Location: E Hall D1
Author(s): Gunter Von Minckwitz, Eric Hahnen, Peter A. Fasching, et al.
Full blood samples with sufficient amount of DNA were available in 295 (94%) out of 315 participants of GeparSixto with TNBC. We searched for gBRCA mutations by MLPA and Fluidigm screening for recurrent pathogenic BRCA1/2 alterations. In combination, both methods enable us to detect approximately 60% of all expected mutation carriers. Participants with so far undetected mutations are currently under investigation by employing next generation sequencing (NGS) techniques to detect additional pathogenic germline alterations in BRCA1/2 or other breast cancer predisposing genes. Conclusions: gBRCA mutation and family history are predictors for higher pCR rates after neoadjuvant anthracycline/taxane based chemotherapy in TNBC. Additive effect of carboplatin is most prominent in patients with gBRCA mutation. Updated results after complete gBRCA mutation analysis will be presented at the meeting. Clinical trial information: NCT 01426880.

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Randomized phase II study of weekly paclitaxel with or without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA HER2-negative breast cancer

Abstract No: 1017
Type: Poster Highlights Session
Time 1: Monday June 2, 1:15 PM to 4:15 PM
Author(s): Kenji Tamura, Jun Hashimoto, Hitoshi Tsuda, et al.
Patients with stage II-IIIA HNBC were randomly assigned to preoperatively CP-CEF arm (4 cycles of CBDCA [area under the curve 5 mg/mL. min, day 1, every 3 weeks] and wPTX [80 mg/m², day 1, 8, 15, every 3 weeks] followed by 4 cycles of CEF [500/100/500 mg/m², day 1, every 3 weeks], or P-CEF arm (4 cycles of wPTX followed by 4 cycles of CEF). The primary endpoint was pCR rate. Breast tumor tissues by preoperative biopsy were tested for Ki-67, EGFR, Cytokeratin (CK) 5/6, BRCA1, vimentin, ERCC1 and ZEB1 by immunohistochemistry (IHC). Conclusions: Adding CBDCA to neoadjuvant wPTX followed by CEF for HNBC statistical significantly improved pCR rate with a favorable safety profile. EGFR expression by IHC is a potent predictive biomarker of response to the CP-CEF regimen as NAC. Clinical trial information: 000003355.

TBCRC028: A phase Ib/II trial of GDC-0941 (a PI3K inhibitor) in combination with cisplatin in metastatic androgen receptor-negative triple-negative breast cancer (TNBC)

Abstract No: TPS1148
Session: Breast Cancer – Triple-Negative/Cytotoxics/Local Therapy
Type: General Poster Session
Time: Monday June 2, 8:00 AM to 11:45 AM
Author(s): Vandana Gupta Abramson, Brian Lehmann, Ingrid A. Mayer, et al.
Background: We recently reported six distinct molecular subtypes of TNBC, including two basal-like subtypes with cell cycle and DNA damage response (DDR) gene expression (GE) signatures (BL1 and BL2) and a luminal androgen receptor (LAR) subtype which expresses AR by immunohistochemistry. BL1 and BL2 cell lines respond to DNA damaging agents, including cisplatin. Consistent with the frequent alterations in DDR and PI3K pathways in TNBC, the combination of cisplatin and the pan-PI3K inhibitor GDC0941 was very active against AR-negative TNBC cell lines in preclinical studies. This trial will evaluate the benefit of the addition of GDC-0941 to cisplatin in patients with metastatic AR-TNBC. Methods: This is an open-label phase Ib/II multiple institution trial in which patients with metastatic AR-TNBC will be randomized to: a) cisplatin 25 mg/m² on days 1, 8, and 15 of a 28 day cycle, or b) cisplatin with GDC-0941. Biopsy of a metastatic lesion at baseline, at day 5-10, and at progression is required. Staging scans will be performed at baseline and every 2 cycles thereafter. Upon progression, patients on the cisplatin arm have the option to crossover to the combination arm with GDC-0941. The primary objectives are: to determine the safety and tolerability of cisplatin + GDC-0941 in patients with AR-TNBC (phase Ib) and efficacy, as measured by the overall response rate (phase II). Secondary objectives are to determine the clinical benefit rate and time to disease progression of both study arms. Correlative analyses will evaluate mechanisms of inherent and acquired resistance. Gene expression profiling to assign a TNBC subtype and whole exome analysis will be performed; the predictive effects of PI3K pathway mutations (PIK3CA, AKT, PTEN) will also be examined. Approximately 125 patients will be enrolled (80% power to detect a 20% improvement in the ORR with a type 1 error of 0.05). Clinical trial information: NCT01918306.

Triple-negative breast cancer subtypes and pathologic complete-response rate to neoadjuvant chemotherapy: Results from the GEICAM/2006-2003 study

Abstract No: 1024
Type: Poster Highlights Session
Time 1: Monday June 2, 1:15 PM to 4:15 PM
Location 1: E354b
Author(s): Angela Santonja, Joan Albanell, Jose Ignacio Chaconet al.
The GEICAM/ 2006-03 study evaluated a regimen of anthracyclines and taxanes +/- carboplatin in the neoadjuvant treatment of patients (pts) with TNBC (Alba, BCRT 2012). We determined TNBC molecular subtypes in FFPE pre-treatment tumor biopsies from pts recruited in this study. Gene expression profile was determined using HTA 2.0 arrays (Illumina). Subtypes were identified with the online tool TNBC type (http://cbc.mc.vanderbilt.edu/tnbc). Finally, we explored the association of the Lehmann subtypes with the pathological complete response (pCR) in breast and axilla (Miller and Payne criteria) using Fisher’s exact test. Conclusions: Our preliminary findings suggest that TNBC subtypes can predict tumor response to neoadjuvant CHT, supporting their potential clinical utility in diagnosis, treatment selection and drug development, bringing TNBC pts a step closer to personalized medicine.

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