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Background: Triple negative breast cancers (TNBCs) are an aggressive and diverse subgroup with no specific targeted therapies currently available. Basal TNBCs show some phenotypic and molecular similarities with germline BRCA mutated BC (gBRCA). In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow PARP inhibitors (olaparib) to work more effectively. PARTNER was designed to establish if the addition of olaparib to neoadjuvant platinum-based chemotherapy for gBRCA and/or basal TNBC is safe and improves efficacy (pathological complete response (pCR)). This is the first time a clinical trial provides safety data of the combination of olaparib with platinum and taxane chemotherapy in an early breast cancer setting. Methods: PARTNER is a 3-stage open label randomised Phase II/III trial of neoadjuvant Carboplatin AUC5 with weekly Paclitaxel 80mg/m2 (CP) +/- olaparib (O) 150mgBD for 12 days x 4 cycles, followed by clinicians' choice of anthracycline regimen x 3 cycles. Basal-TNBC and/or gBRCA patients are eligible for inclusion. Primary endpoints are defined by stage: Stage 1 - Safety, Stage2 - Schedule selection, and Stage 3 - Efficacy (pCR rate). The trial is now powered for efficacy analysis in the BRCA and non-BRCA population independently. Stage 1 and 2 randomization was(1:1:1) to CP: CP + O from day (D) -2: or CP + O from D 3. G-CSF was mandatory during the first 4 cycles of treatment. We present a pooled-safety analysis from Stage 1 and 2 of the two research arms only. Recruitment continues into Stage 3. Results: Between June 2016 and April 2018, 159 patients were recruited among the three arms. Overall, median age was 48.2 [range 22.3- 70.9]; 12% had Tumours >5cm, 34% had Axillary involvement; 17% were gBRCA. Adverse events (AE) that were reported as common (in at least 10% of patients) were Anaemia 23%, Neutropenia 18% and Infection 10%. Fatigue and Diarrhoea were next most prevalent with 9% and 6% respectively. The most common AE Grade >=3 were haematological events. These include Neutropenia 19%, Anaemia 15%, and Thrombocytopenia 5%. Febrile Neutropenia and Haemorrhage were reported in only 2% and 1% of cases. Grade 3 Non- haematological events were Fatigue 7%, Hypertension 3%, Headache 3% and Diarrhoea 2%. Grade 3 Sensory neuropathy was present in 2% of patients. No grade 4 sensory or motor neuropathy events were described. Serious adverse reactions related to investigational regimen were reported in 17% of patients and include fever and infection with 8 and 4 events respectively. No toxicity related deaths were reported. As per July 8th 2019, 373 patients have been recruited from which 58 were gBRCA. Conclusions: Combinations of olaparib with neoadjuvant CP chemotherapy showed an acceptable and manageable toxicity profile. Although haematological events were the most common, they did not exceed historical frequencies reported for standard chemotherapy regimens. Final safety analysis will be performed once recruitment is complete and will include detailed long-term neuropathy data. Citation Format: Karen Pinilla Alba, Emma McMurtry, Anne-Laure Vallier, Louise Grybowicz, Ellen Copson, Anne Armstrong, Rebecca Roylance, Wendi Qian, Nikolaos Demiris, Stanly Thomas, Caron Harvey, Luke Hughes-Davies, Karen McAdam, Paula del Rosario, Bryony Harrop, Elena Provenzano, Marc Tischkowitz, Helena M Earl, Jean E Abraham. Preliminary safety data from stage 1 and 2 of the phase II/III PARTNER trial: Addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-10-05.

The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists’ reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57–0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation of residual cancer burden was a simple and reproducible method of quantifying response to neoadjuvant chemotherapy as demonstrated by performance comparison of the two pathologists.

Background: No specific targeted therapies are available for Triple Negative Breast Cancers (TNBC), an aggressive and diverse subgroup. The basal TNBC subgroup show some phenotypic and molecular similarities with germline BRCA (gBRCA). In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow drugs called PARP inhibitors (olaparib) to work more effectively. Aims: To establish if the addition of olaparib to neoadjuvant platinum based chemotherapy for basal TNBC and/or gBRCA breast cancer is safe and improves efficacy (pathological complete response (pCR)). Trial design: 3 stage open label randomised phase II/III trial of neoadjuvant paclitaxel and carboplatin +/olaparib, followed by clinicians' choice of anthracycline regimen. Stage 1 and 2: Patients are randomised (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 for 4 cycles) or one of two research arms with the same chemotherapy regimen but with two different schedules of olaparib 150mg BD for 12 days. Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. Methods: Stage 1 Safety: both research arms combined. Stage 2 Schedule selection criteria: pCR rate and completion rate of olaparib protocol treatment. It is a “pickthewinner” design with 53 patients in each research arm. This allows a 90% power, 5% onesided significance level to test null hypothesis of pCR ≤35% versus an alternative hypothesis of pCR ≥55% in each of the research arms. Stage 3 Efficacy:anticipated pCR ˜55-60% for all trial patients and ˜60-65% for gBRCA patients. The trial is powered to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to chemotherapy (enriched design). TNBC patient recruitment will be capped, to ensure required gBRCA patients are enrolled. Enrichment design is applied with overall significance level 0.05(α) = 0.025(αall)+ 0.025(αgBRCA) and 80% power. Target accrual: 527 [gBRCA 220] Current accrual: 56 Sites activated: 15 [expected number of sites 30-50]. Citation Format: Abraham J, Vallier A-L, Qian W, Grybowicz L, Thomas S, Machin A, Harvey C, Chiu E, McAdam K, Hughes-Davies L, Roylance R, Copson E, Armstrong A, Provenzano E, Tischkowitz M, McMurtry E, Earl H. PARTNER randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [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 OT3-04-03.

Background: No specific targeted therapies are available for Triple Negative Breast Cancers (TNBC), an aggressive and diverse subgroup. The basal TNBC sub-group share some phenotypic and molecular similarities with germline BRCA (gBRCA) tumours. In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow drugs called PARP inhibitors (Olaparib) to work more effectively. Aims: To establish if the addition of olaparib to neoadjuvant platinum based chemotherapy for basal TNBC and/or gBRCA breast cancer is safe and improves efficacy (pathological complete response (pCR)). Methods: Trial design: 3-stage open label randomised phase II/III trial of neoadjuvant paclitaxel and carboplatin +/- olaparib, followed by clinicians' choice of anthracycline regimen. Stage 1 and 2: Randomisation (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 for 4 cycles) or one of two research arms with the same chemotherapy regimen but with two different schedules of olaparib 150mg BD for 12 days. Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. End-points: Stage 1: Safety; Stage 2: Schedule selection using pCR rate and completion rate of olaparib using a “pick-the-winner” design. Stage 3: pCR rate. Enrichment design is applied with an overall significance level 0.05(α) and 80% power. A total of 527 patients will be included to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to platinum based chemotherapy. Trial Progress: PARTNER has been recruiting in UK since 27th May 2016. IDSMC recommended to continue the trial without change after reviewing the Stage 1 safety data. The recruitment of stage 2 was completed in April 2018 and results to be reviewed by the IDSMC in early 2019. The trial is open and enrolling patients to national and international sites. Citation Format: Abraham J, Vallier A-L, Qian W, Machin A, Grybowicz L, Thomas S, Weiss M, Harvey C, McAdam K, Hughes-Davies L, Roberts A, Roylance R, Copson E, Pinilla K, Armstrong A, Provenzano E, Tischkowitz M, McMurty E, Earl H. PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [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 OT3-03-03.

Background: In patients with TNBC, following standard neoadjuvant chemotherapy, residual disease (RD) is correlated with poor prognosis and 50% relapse within 5 years [1]. PARTNER is a neoadjuvant clinical trial which randomises TNBC and gBRCAm patients to carboplatin and paclitaxel +/- olaparib followed by anthracycline-based chemotherapy. Patients with RD after neoadjuvant treatment in this trial also face poorer survival outcomes, due to the paucity of treatment options. PARTNERING, develops a new strategy using novel agent combinations as an alternative pathway for patients with RD within the PARTNER trial. Methods: PARTNERING is a phase II open label, sub-study with a two-stage Simon design with biomarker guided treatment cohorts open only to patients in the PARTNER trial. A maximum of 15 patients will be included in each cohort. Patients with RD > 10% tumour cellularity (TC) on biopsy after neoadjuvant therapy will be eligible. Patients who have no tumour cells or < 10% TC, and those with progressive disease will be excluded. Allocation of patients into the cohorts will be based on tumour infiltrating lymphocytes (TILs) expression either on diagnostic or post treatment biopsy. Patients with tumours with TILs score ≤20% are considered “non-immunogenic” They will be stratified according to HRD status and allocated to receive a cell cycle checkpoint inhibitor + olaparib. Patients with a TILs score >20% are considered “immunogenic” and will be allocated to receive an immune checkpoint inhibitor with olaparib or a cell cycle checkpoint inhibitor. Primary outcome measure is pCR / MRD rate at surgery after the administration of 2 cycles / 8 weeks of a combination of new agents. The rate of conversion to pCR/MRD will be correlated with TC, TILs, BRCA and homologous recombination deficiency (HRD) status, Ki67% and previous olaparib treatment. Progress: The PARTNERING pathway in the PARTNER trial will be open late 2018. Citation Format: Abraham JE, Vallier A-L, Qian W, Machin A, Grybowicz L, Thomas S, Weiss M, Harvey C, McAdam K, Hughes-Davies L, Roberts A, Provenzano E, Pinilla K, Roylance R, Copson E, Armstrong A, McMurtry E, Tischkowitz M, Earl HM. PARTNERING / PARTNER : Phase II sub-study to establish if the addition of combinations of new agents (olaparib, cell cycle and immune checkpoint inhibitors) can improve the rate of pathological complete response (pCR) and minimal residual disease (MRD) in triple negative breast cancer (TNBC) and / or germline BRCA mutated (gBRCAm) patients with evidence of residual disease after PARTNER therapy [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 OT3-01-02.

Background: The ARTemis trial was developed to assess the efficacy and safety of adding bevacizumab to standard neoadjuvant chemotherapy in HER2-negative early breast cancer.Methods: In this randomised, open-label, phase 3 trial, we enrolled women (≥18 years) with newly diagnosed HER2-negative early invasive breast cancer (radiological tumour size >20 mm, with or without axillary involvement), at 66 centres in the UK. Patients were randomly assigned via a central computerised minimisation procedure to three cycles of docetaxel (100 mg/m2 once every 21 days) followed by three cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) once every 21 days (D-FEC), without or with four cycles of bevacizumab (15 mg/kg) (Bev+D-FEC). The primary endpoint was pathological complete response, defined as the absence of invasive disease in the breast and axillary lymph nodes, analysed by intention to treat. The trial has completed and follow-up is ongoing. This trial is registered with EudraCT (2008-002322-11), ISRCTN (68502941), and ClinicalTrials.gov (NCT01093235).Findings: Between May 7, 2009, and Jan 9, 2013, we randomly allocated 800 participants to D-FEC (n=401) and Bev+D-FEC (n=399). 781 patients were available for the primary endpoint analysis. Significantly more patients in the bevacizumab group achieved a pathological complete response compared with those treated with chemotherapy alone: 87 (22%, 95% CI 18–27) of 388 patients in the Bev+D-FEC group compared with 66 (17%, 13–21) of 393 patients in the D-FEC group (p=0·03). Grade 3 and 4 toxicities were reported at expected levels in both groups, although more patients had grade 4 neutropenia in the Bev+D-FEC group than in the D-FEC group (85 [22%] vs 68 [17%]).Interpretation: Addition of four cycles of bevacizumab to D-FEC in HER2-negative early breast cancer significantly improved pathological complete response. However, whether the improvement in pathological complete response will lead to improved disease-free and overall survival outcomes is unknown and will be reported after longer follow-up. Meta-analysis of available neoadjuvant trials is likely to be the only way to define subgroups of early breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.Funding: Cancer Research UK, Roche, Sanofi-Aventis.

TPS591 Background: No specific targeted therapies are available for Triple Negative Breast Cancers (TNBC), an aggressive and diverse subgroup. The basal TNBC sub-group show some phenotypic and molecular similarities with germline BRCA (gBRCA). In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow drugs called PARP inhibitors (olaparib) to work more effectively. Aims: To establish if the addition of olaparib to neoadjuvant platinum based chemotherapy for basal TNBC and/or gBRCA breast cancer is safe and improves efficacy (pathological complete response (pCR)). Trial design: 3-stage open label randomised phase II/III trial of neoadjuvant paclitaxel and carboplatin +/- olaparib, followed by clinicians' choice of anthracycline regimen. Stage 1 and 2: Patients are randomised (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 for 4 cycles) or one of two research arms with the same chemotherapy regimen but with two different schedules of olaparib 150mg BD for 12 days. Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. Methods: Stage 1 - Safety: both research arms combined. Stage 2 - Schedule selection criteria: pCR rate and completion rate of olaparib protocol treatment. It is a “pick-the-winner” design with 53 patients in each research arm. This allows a 90% power, 5% one-sided significance level to test null hypothesis of pCR ≤35% versus an alternative hypothesis of pCR ≥55% in each of the research arms. Stage 3 - Efficacy: anticipated pCR ~55-60% for all trial patients and ~60-65% for gBRCA patients. The trial is powered to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to chemotherapy (enriched design). TNBC patient recruitment will be capped, to ensure required gBRCA patients are enrolled. Enrichment design is applied with overall significance level 0.05(α) = 0.025(αall)+ 0.025(αgBRCA) and 80% power. Target accrual: 527 [gBRCA 220] Current accrual: 17 Sites activated: 12 [expected number of sites 30-50].

Background: Triple Negative Breast Cancers (TNBC) are a biologically diverse and aggressive sub-group. Early effective treatment can lead to cure. Current standard treatment is systemic chemotherapy either pre-/post-definitive surgery. No specific targeted therapies are available for TNBC. There are phenotypic and molecular similarities between germline BRCA (gBRCA) breast cancer and TNBC. In TNBC 10%-20% harbour gBRCA mutations. In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways allow drugs called PARP inhibitors (olaparib) to work particularly effectively. Aims: To establish if the addition of olaparib to neoadjuvant platinum-based chemotherapy for TNBC and/or gBRCA breast cancer is safe and improves efficacy. Trial design: 3-stage open label randomised phase II/III trial of neoadjuvant olaparib +/- platinum containing chemotherapy followed by clinicians' choice of anthracycline regimen. Stage 1 and 2, patients are randomised (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 chemotherapy - 4 cycles) or one of two research arms which uses the same chemotherapy regimen but with two different schedules of olaparib 150mg BD). Stage 3: patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. Primary outcome measures: Stage 1: safety of the addition of olaparib to chemotherapy. Prophylactic G-CSF is mandatory. Stage 2: pathological complete response (pCR) in each of the two research arms. At the end of stage 2, one of the research arms will be dropped. Stage 3: pCR at surgery after neoadjuvant treatment. pCR - defined as no residual invasive carcinoma within the breast (ductal carcinoma in situ permitted) AND no evidence of metastatic disease within the lymph nodes. Eligibility: •Aged 16 to 70. •Written informed consent. •Histologically confirmed invasive breast cancer. •Clinical stage T1-4 N0-2 (tumour or metastatic node diameter>10mm) •Confirmed ER-negative and HER2-negative or gBRCA mutation positive, irrespective of hormone status. •Performance Status 0-1 Statistical Methods: Stage 1, Safety: both research arms combined. Stage 2, Schedule selection criteria: pCR rate and completion rate of olaparib protocol treatment. It is a “pick-the winner” design with 53 patients in each research arm. This allows a 90% power, 5% one-sided significance level to test null hypothesis of pCR ≤35% versus an alternative hypothesis of pCR ≥55% in each of the research arms. Stage 3, Efficacy: anticipated pCR ∼45-55% for all trial patients and ∼50-60% for gBRCA patients. The trial is powered to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to chemotherapy (enriched design). TNBC patient recruitment will be capped, to ensure the required number of gBRCA patients are enrolled. Enrichment design is applied with the overall significance level 0.05(α)=0.025(αall)+ 0.025(αgBRCA) and 80% power. Present accrual: 1 [Trial opened: 23rd May 2016] Target accrual: 527 (TNBC 307; gBRCA 220) Contact information: Dr. Jean Abraham; Email: ja344@medschl.cam.ac.uk. Citation Format: Abraham JE, Vallier A-L, Qian W, Grybowicz L, Thomas S, Mahmud S, Harvey C, McAdam K, Hughes-Davies L, Roylance R, Copson E, Brown J, Provenzano E, Tischkowitz M, Earl HM. PARTNER - Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [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 OT2-01-15.

Background: Bevacizumab (bev) has been used with neo-adjuvant chemotherapy (NACT) in breast cancer trials. Geparquinto reported benefit for bev in triple negative (neg) patients (pts) (pathological complete response (pCR) 36.4% vs 27.8% p=0.02), as did CALGB 40603 (pCR 52% vs 44%, p=0.057), although NSABP-B40 showed benefit in ER positive (pos) pts (pCR 23.3% vs 15.2%, p=0.008). Methods: 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; 85% power, 5% alpha level. Results: 800 pts were randomised from 66 UK centres (May 2009 to Jan 2013). 68% were D→FECBev+D→FEC % (95%CI)% (95%CI)p *$pCR in all breast tumours AND absence of disease in ax LNs in all breast tumours(n=66/393)(n=87/388) 17% (13-21%)22% (18-27%)0.03 ER neg (Allred 0-2) (n=253)32% (24-41)44% (36-54) ER weak pos (Allred 3-5) (n=67)26% (13-44)52% (34-69) ER strong pos (Allred 6-8) (n=461)7% (4-11)6% (3-10) pCR or MRD in all breast tumours(n=114/394)(n=138/388) 29% (25-34%)36% (31-41%)0.035 ER neg (Allred 0-2) (n=254)45% (36-54)56% (47-65) ER weak pos (Allred 3-5) (n=67)44% (27-62)73% (54-87) ER strong pos (Allred 6-8) (n=461)18% (13-23)19% (14-24) * Adjusted for stratification variables. $ Primary endpoint for the ARTemis trial Conclusions: ARTemis showed a significant improvement in both pCR and MRD rates 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 and MRD rates in ER-strong pos pts were lower and did not appear to benefit from bev. Our results are similar to those reported in Geparquinto and CALGB 40603. Citation Format: Helena M Earl, Louise Hiller, Janet A Dunn, Clare Blenkinsop, Louise Grybowicz, Anne-Laure Vallier, Jean Abraham, Jeremy Thomas, Elena Provenzano, Luke Hughes-Davies, Karen McAdam, Stephen Chan, Rizvana Ahmad, Tamas Hickish, Stephen Houston, Daniel Rea, John Bartlett, Carlos Caldas, David Cameron, Larry Hayward. ARTemis: A randomised trial of bevacizumab with neo-adjuvant chemotherapy for patients with HER2-negative early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD2-3.

1014Background: ARTemis compared the addition of Bev to neoadjuvant D-FEC in HER2 negative breast cancer. Improved pathological complete response (pCR) with Bev has been reported previously. Method...

1014 Background: Bevacizumab (bev) has been used with NACT in breast cancer trials. Geparquinto reported benefit for bev in triple negative (neg) patients (pts) (pCR 36.4% v 27.8% p=0.02), as did C...

Methods Neo-tAnGo and ARTemis are national 800-patient breast cancer trials assessing neo-adjuvant chemotherapy regimens, both with a secondary endpoint of radiological tumour response, assessing treatment effect in terms of change in tumour size. Both trials record radiological sizes at baseline, mid-way through and at the end of the chemotherapy regimens. Neo-tAnGo (randomising Jan’05 to Sept’07) recorded mammograms and/or ultrasounds and/or MRI scans, identifying up to two breast and one axillary lesion as ‘target’ lesions. At each of the 3 time-points and for each target lesion, the scan types and largest diameters observed (maximum of two) were reported, along with a clinical judgement of response. ARTemis (randomising May’09 to Jan’13) recorded ultrasounds only, recording the longest single diameter of each tumour (including axillary tumours) along with total ‘tumour bulk’ in each breast. At midand endchemotherapy, a clinical judgement of response per breast is also recorded.

Background: Bevacizumab, a humanised monoclonal antibody which targets vascular endothelial growth factor (VEGF), has shown promising anti-tumour effect when given concurrently with taxane-based chemotherapy in breast cancer. However two neoadjuvant breast cancer trials have produced conflicting results. The GEPARQUINTO trial reported significant benefit only in the triple negative patients (pCR 27.8% vs 36.4% p = 0.021). The NSABP-B40 study showed significant benefit for bevacizumab only in the ER+ve patients (pathological complete response (pCR) in ER+ve population 15.2% vs 23.3%, p = 0.008). Trial design: ARTemis is a phase III randomised trial to determine whether the addition to neo-adjuvant chemotherapy of bevacizumab is more effective than standard chemotherapy alone in patients with HER2-negative early breast cancer. A total of 400 patients will be randomised into each of the two treatment arms which will allow an absolute difference in the pCR rates in excess of 10% to be detected at the 5% (2-sided) level of significance with an 85% power. Primary outcome is pathological complete response rates after neo-adjuvant chemotherapy, i.e. no residual invasive carcinoma in the breast, and no evidence of metastatic disease within the lymph nodes. Secondary outcomes are disease free survival, overall survival, complete pathological response rates in breast alone, radiological response after 3 and 6 cycles of chemotherapy and rate of breast conservation and toxicities. Translational work (ARTemis-Science): collection of blood samples, and paraffin-embedded formalin-fixed and fresh tissue samples to investigate whether markers for chemotherapy response/resistance, and pharmacogenetic and pharmacogenomic markers can be correlated with outcomes (pathCR and RFS) in patients randomised to receive bevacizumab versus those that do not. Eligibility criteria: Histologically confirmed HER2-negative invasive breast cancer; T2 to T4 tumour and/or large/fixed axillary nodes (>20mm/clinical N2 or N3), or inflammatory disease; suitable for, and fit to receive neo-adjuvant chemotherapy and an anti-angiogenic. Results: Recruitment into ARTemis began in April 2009 and as of June 2012 had recruited 600 (75%) patients and 65 sites are open for recruitment. ARTemis is due to complete recruitment by first quarter of 2013 and the first planned interim analysis of the primary outcome will be December 2013. Conclusion: The IDSMC reviewed the trial in June 2012 and recommended continuation of recruitment to this important trial given there were no safety concerns. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-09.

TPS1144 Background: Bevacizumab is a new humanised monoclonal antibody which targets vascular endothelial growth factor (VEGF) and thereby the neoangiogenic process in cancer. Bevacizumab has shown promising anti-tumour effect when given concurrently with taxane-based chemotherapy in breast cancer. However two neoadjuvant breast cancer trials have produced conflicting results. The NSABP-B40 study showed significant benefit for bevacizumab only in the ER+ve patients (pathological complete response (pCR) in ER+ve population 15.2% vs 23.3%, p=0.008). Whereas the GEPARQUINTO trial reported significant benefit only in the triple negative patients (pCR 27.8% vs 36.4% p=0.021). Methods: ARTemis is a phase III randomised trial to determine whether the addition to neo-adjuvant chemotherapy of bevacizumab is more effective than standard chemotherapy alone in patients with HER2-negative early breast cancer. A total of 400 patients will be randomised into each of the two treatment arms which will allow an absolute difference in the pCR rates in excess of 10% to be detected at the 5% (2-sided) level of significance with an 85% power. Primary outcome is pathological complete response rates after neo-adjuvant chemotherapy, i.e. no residual invasive carcinoma in the breast, and no evidence of metastatic disease within the lymph nodes. Secondary outcomes are disease free survival, overall survival, complete pathological response rates in breast alone, radiological response after 3 and 6 cycles of chemotherapy and rate of breast conservation and toxicities. Results: Recruitment into ARTemis began in April 2009 and as of January 2012 had recruited 469 (59%). ARTemis is due to complete recruitment by Dec 2012 and the first planned interim analysis of the primary outcome will be Dec 2013. Conclusion: The IDSMC reviewed the trial in June 2011 and recommended continuation of recruitment to this important trial given there were no safety concerns, and results from the other neoadjuvant studies (NSABP-B40 and GEPARQUINTO) are conflicting.