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Introduction Neoadjuvant chemotherapy (NAC) in breast cancer is an in vivo marker of chemosensitivity and pathological complete response (pCR) an independent prognostic factor. When there is response, NAC downstages the tumour and may allow for or facilitate a conservative surgery. There are three histological patterns of response to NAC: a concentric pattern in which tumour regression takes place from the periphery to the center, a scatter pattern, where fibrosis is placed between tumoral cells, and a mixed pattern. Objective To determine which clinical and histological variables define the type of response to neoadjuvant chemotherapy that facilitates and allows for breast conservation in women with breast cancer. Material and methods A retrospective observational study was made including 170 patients with breast cancer who underwent NAC in the Hospital Universitari de Bellvitge between February 2010 and October 2013. Different clinicopathological parameters were recorded: age, menopausal, stage, surrogate molecular subtype, histological pattern of response, and pCR. Median age was 50 (23-78),Stage I (1.1%) IIA (27.1%) IIB (35%), IIIA (20.9%), IIIB (11.4%), IIIC (4.5%). Molecular subrogated types: Triple negative (30.7%), Luminal B Her 2 negative like (26.2%), Her 2 positive (17.7%), Luminal B Her 2 positive like (16.4%) and Luminal A like tumours (9.0%).NAC included Anthracyclines, Taxanes, and Trastuzumab if Her 2 +++. Results: Histological pattern of response: 25,5% of cases achieved a pCR. When residual tumour was observed, 42% of the cases were as scatter pattern, 21.9% as concentric pattern and 8.9% as mixed pattern. The predictive factors of pCR were in the univariate analysis: absence of multicentricity, negative estrogen receptor, negative progesterone receptor, histological grade 3, Ki 67 > 20%, and her 2 overexpression. In the multivariate analysis, only negative estrogen receptor and her 2 overexpression were predictive factors. The molecular surrogate type Her 2 positive was predictive of pCR. The predictive factors of the concentric response were in the univariate analysis: tumour size of < 5 cm, absence of nodal involvement, negative estrogen receptor, negative progesterone receptor, presence of tumour necrosis and inflammatory infiltration. In the multivariate analysis, tumour size < 5 cm, absence of lymph node involvement, Ki 67 > 20% and tumour necrosis were statistically significative. The molecular surrogated type predictive of a concentric response was triple negative. Conservative surgery was more frequent in the concentric pattern group (78.4%) than in the scatter pattern (58.1%) (p=0.032) but the histological pattern of response to NAC is not correlated to survival. Conclusions Tumour size < 5 cm, absence of lymph node involvement, Ki 67 > 20% and tumour necrosis were predictive of concentric pattern of response to NAC. Triple negative tumours were related to concentric histological pattern, meanwhile Her 2 overexpressed was predictive of pCR. The conservative treatment was more frequent in the concentric pattern. Histological pattern of response to NAC is not correlated to outcome. Only pCR was related to survival. Citation Format: Pla Farnós M-J, García Tejedor A, Fernández Montolí ME, Campos Delgado M, Soler Monsó T, Petit Montserrar A, Morilla Ruiz I, Gil Gil M, Falo Zamora C, Ortega Martinez R, Gumà Martinez A, Perez Martin X, Ponce Sebastià J. Histological patterns of response to neoadjuvant chemotherapy in breast cancer and breast conservation [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 P1-15-09.

Background: The oral AKT inhibitor IPAT is being evaluated in cancers with a high prevalence of PI3K/AKT pathway activation. In the PBO-controlled randomized phase II FAIRLANE trial (NCT02301988), adding IPAT to PAC as neoadjuvant therapy for TNBC led to a numerical increase in pathologic complete response (pCR) in unselected patients (17.1% vs 13.3%), with a greater treatment effect in patients with PIK3CA/AKT1/PTEN-altered tumors (17.9% vs 11.8%). The addition of IPAT also led to an increase in complete response (CR) by MRI (27.6% vs 13.3%) that was enhanced in patients with PIK3CA/AKT1/PTEN-altered tumors (39.3% vs 8.8%) [Oliveira, AACR 2018]. We report an exploratory analysis performed to provide better understanding of potential biomarkers for response. Methods: Pretreatment tumor samples were evaluated for genomic alterations using the FoundationOne® (Foundation Medicine) assay (n=144) and gene expression by RNA-Seq (n=92). Samples were classified into TNBC subtypes based on the method developed by Lehmann and Pietenpol [Lehmann, J Clin Invest 2011]. Tumor-infiltrating lymphocytes (TILs) were quantified using the Salgado method [Salgado, Ann Oncol 2015] (n=135). Results: Of 62 patients (43%) with PIK3CA/AKT1/PTEN-altered tumors, 21 had an activating mutation in PIK3CA or AKT1 and 47 had an alteration in PTEN (6 [3 in each arm] had both PIK3CA mutation and PTEN alteration). Although only 3 patients with PIK3CA/AKT1-mutant tumors achieved a pCR, there was an increased rate of MRI CR with the addition of IPAT to PAC [Table]. In patients with PTEN alterations, both pCR rate and MRI CR rate were increased with IPAT. In patients treated with PBO + PAC, all 4 pCR patients evaluable by RNA-Seq were of the immunomodulatory (IM) subtype. However, in the IPAT + PAC arm, pCRs were also seen in patients with basal-like 1 (BL-1), mesenchymal (M), and mesenchymal stem-like (MSL) subtypes. Consistent with this observation, in the PBO + PAC arm, samples from patients achieving a pCR had significantly higher levels of stromal TILs than those from patients who did not have a pCR, while no difference was observed in the IPAT + PAC arm. Response, n (%)PIK3CA/AKT mutation (n=21)PTEN alteration (n=47) IPAT + PAC (n=11)PBO + PAC (n=10)IPAT + PAC (n=21)PBO + PAC (n=26)pCR1 (9%)2 (20%)4 (19%)3 (12%)CR by MRI5 (45%)1 (10%)8 (38%)2 (8%) Conclusions: This retrospective exploratory biomarker analysis of the phase II FAIRLANE trial of neoadjuvant IPAT for TNBC provides insight into the potential heterogeneity of response and resistance to taxane therapy. The results also hint that response to PAC alone is dependent on baseline immune infiltration and that this dependency might be relieved with the addition of AKT inhibition. Citation Format: Wongchenko MJ, Oliveira M, Saura C, Nuciforo P, Calvo I, Andersen J, Passos Coelho JI, Gil Gil M, Bermejo B, Patt DA, Ciruelos E, Singel SM, Maslyar DJ, Xu N, de la Peña L, Baselga J, Gendreau S, Isakoff SJ. Exploratory biomarker analyses of FAIRLANE, a double-blind placebo (PBO)-controlled randomized phase II trial of neoadjuvant ipatasertib (IPAT) + paclitaxel (PAC) for early triple-negative breast cancer (TNBC) [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 P2-08-19.

BACKGROUND FGFR mutations and translocations occur in approximately 10% of glioblastomas (GBMs). FGFR3-TACC3 fusion has been reported as predictive of response to FGFR tyrosine kinase inhibitor therapy both pre-clinically and clinically. Infigratinib (BGJ398) is a selective small-molecule pan-FGFR kinase inhibitor that has demonstrated anti-tumor activity in several solid tumors with FGFR genetic alterations. Therefore, we conducted a phase II trial to test the efficacy of infigratinib in FGFR-altered recurrent GBM (NCT01975701). METHODS This open-label trial accrued adults with recurrent high-grade gliomas following failure of initial therapy that harbored FGFR1-TACC1 or FGFR3-TACC3 fusions; activating mutations in FGFR1, 2 or 3; or FGFR1, 2, 3, or 4 amplification. Oral infigratinib was administered 125 mg on days 1–21 every 28 days. Prophylaxis for hyperphosphatemia, a common toxicity, was recommended. The primary endpoint was the 6-month progression-free survival (6mPFS) rate by RANO (locally assessed, estimated by K-M method), with a goal of >40%. RESULTS As of the Sep 2017 data cut-off, 26 patients (16 men, 10 women; median age 55 years, range 20–76 years; 50% with ≥2 prior regimens) were treated, and 24 (92.3%) discontinued for disease progression (n=21) or other reasons (n=3). All patients had FGFR1 or FGFR3 gene alterations, and 4 had >1 gene alteration. The estimated 6mPFS rate was 16% (95% CI 5.0–32.5%); median PFS was 1.7 months (95% CI 1.1–2.8 months); median OS was 6.7 months (95% CI 4.2–11.7 months); ORR was 7.7% (95% CI 1.0–25.1%). The best overall response was: partial response 7.7% (FGFR1 mutation n=1; FGFR3 amplification n=1); stable disease 26.9%; progressive disease 50.0%; missing/unknown 15.3%. The most common (>15%) all-grade treatment-related adverse events (AEs) were hyperphosphatemia, fatigue, diarrhea, hyperlipasemia, and stomatitis. There were no grade 4 treatment-related AEs. Eleven patients (42.3%) had treatment-related AEs requiring dose interruptions or reductions (most commonly hyperphosphatemia). CONCLUSIONS Infigratinib induced partial response or stable disease in approximately one-third of patients with recurrent GBM and/or other glioma subtypes harboring FGFR alterations. Most AEs were reversible and manageable. Further potential combinations are being explored in patients with proven FGFR-TACC fusion genes and analysis of biomarker data is ongoing.

Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics. Women with invasive incident breast cancer identified from the Patient’s Hospital Discharge Database [174.0–174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery. Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months’ follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women. Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months’ follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies.

BACKGROUND Standard treatment of glioblastoma (GBM) is focal radiation with concomitant and adjuvant temozolomide (TMZ) for 6 cycles. The GEINO-14-01 trial (NCT02209948) investigated the role of extending adjuvant TMZ to 12 cycles in a randomized multicenter study. MATERIAL AND METHODS Between Aug/2014 and Nov/2018, 166 patients (p) were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment to 12 cycles after proving stable disease in the MRI performed before inclusion. The trial was stratified by MGMT status and presence or absence of residual disease (defined as a residual enhancement larger than 1cm on the MRI). The primary endpoint was differences in 6monthsPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. RESULTS Median age was 60.4 (range 29–83), 97p (61%) were methylated and 83 p (52.2%) were reported with residual disease. Median (m) PFS was 7.9 months (95%CI: 6.1–9.8) and mOS: 20.9 (95%CI: 17.6–24.1). A methylated status was a factor of better PFS (HR=0.29, 95% CI 0.46–0.95; p=0.029) and better OS (HR= 0.43: 95% CI 0.28–0.66; p=0.000) as well as the absence of residual disease (PFS: HR = 0.84: 95% CI =0.71–1.01; p=0.068; OS: HR=0.77, 95%CI 0.63–0.96; p=0.019). We didn’t find any difference in PFS (HR=1.02, 95%CI 0.85–1.21; p=0.82), or OS (HR=0.90; 0.73–1.11; p=0.34) on extending treatment with temozolomide longer than 6 cycles. CONCLUSION There is no benefit of continuing TMZ treatment for more than 6 cycles in the adjuvant treatment of glioblastoma. Final data will be presented at the congress. Supported by a Grant of the ISCIII: PI13/01751

1077 Background: The oral chemotherapy (CT) combination of NVBo and X has shown activity and good tolerability in MBC. H +CT is the standard treatment for HER2-positive MBC. We report the latest re...

BACKGROUND: RANO criteria were applied to evaluate differences in response between the 2 arms: TMZ or TMZ + BEV in a randomized study. We evaluate here the RANO sub-criterion (PI) to evaluate response. METHODS: Between December 2009 and April 2013, p with unresectable GBM, PS < 3 and MMS ≥25 were randomly assigned to receive eitherTMZ (200 mg/m2, days 1–5,for 2 28-day cycles), followed by standard TMZ with concomitant radiotherapy (60Gy) and then adjuvant TMZ for 6 cycles (TMZ Arm), or the same regimen but with the addition of BEV (10mg/kg /15 days) during pre-radiotherapy and concomitant treatment (BEV Arm). The primary endpoint was response according to RANO criteria after the 2 pre-radiotherapy cycles. The study was powered to detect a 30% difference between arms. A centralized revision of MRI's blinded to clinical status of p is ongoing. (ClinicalTrials.gov NCT01102595). RESULTS:103 p were registered and 93 randomized – 45 to the TMZ Arm and 48 to the BEV Arm. All p who received at least one dose of treatment were included in the analysis. Overall response rate (ORR) was evaluated after the 2-pre-radiotherapy cycles. Patients completed pre-radiotherapy treatment in 48.9% (TMZ Arm) vs 66.7% (BEV Arm), p = 0.08. Response was not evaluable in 3p (TMZ arm) and 5p (BEV arm) because of previous toxicity or refuse to continue. ORR by RANO criteria for evaluable p was: Arm TMZ: PR 3 (7.1%) SD 8 (19%) PD 31 (73.8%)., Arm B: PR 11 (25.6%) SD 17 (39.5%) 15 (34.9%) P = 0.001. Response by individual RANO sub criterion (Arm TMZ% vs Arm BEV%).1- MRI IP: PR (8.3 vs 26.2), SD (22.2 vs 42.8), P (69.4 vs 31) (P = 0.003), 2-Neurological status: SD (54.8 vs 79.5), No SD (45.2 vs 20.5) (P = 0.014), 3-Dexametasone dose: stable (60.5 vs 51.2), increase (28.9 vs 4.7), reduction (10.5 vs 44.2) (P < 0.001). CONCLUSION: ORR was significantly higher in the BEV Arm for both for general RANO criteria as for each individual criterion (MRI, clinical stability and dexametasone doses.

13011 Background: Recurrent MG have poor prognosis and low response rates to available treatments. Following data from Vredenburg´s phase II trial (pro ASCO 2005) some centres began to treat recurrent MG with bevacizumab and irinotecan. The aim of this study is to confirm efficacy and safety of this combination in non-selected consecutive patients (pts). Methods: Data from 6 Spanish hospitals was collected retrospectively. All pts were > 18 years, had to sign an informed consent and to present: histological documented MG; progression after radiation and temozolomide; measurable disease on MRI; have received at least 3 infusions of treatment schedule: Irinotecan 125mg/m2 and bevacizumab 10 mg/kg every 2 weeks for a maximum of a year. Response rate (RR) was determinate by MRI (performed every 6 cycles) using McDonald criteria. Progression free survival (PFS) and overall survival (OS) were calculated by Kaplan Meier method. Results: From August 2006 to October 2007, 44 consecutive pts (28 Glioblastoma, 11 An...

603 Background: Primary hormonal therapies have demonstrated great activity in elderly women with locally advanced and hormone-dependent breast tumors. Exemestane, a steroidal aromatase inactivator, is effective in a metastatic setting. The primary aim of this study was to analyze the efficacy of exemestane as a neoadjuvant treatment. Methods: 55 patients (p) were recruited. Inclusion criteria were histologic diagnosis of infiltrating breast carcinoma, no metastatic disease, tumor >3 cm (T2, T3, T4a-b), >50% ER+, and no previous hormonal treatment/chemotherapy. At baseline, all p were considered noneligible for breast-conserving surgery. Treatment: oral exemestane 25 mg/d for 6 months. Response was estimated by mammography and breast ultrasound every 2 months (RECIST criteria). Secondary endpoints were rate of breast-conserving surgery, time to progression, duration of response, and toxicity. To date, 50 p have been evaluated for response and 5 remain under treatment. Results: Patient characteristics: med...

587 Background: Preclinical studies show synergistic activity between N and H and several clinical trials have confirmed that this combination is active and safe for HER2+MBC patients. Here we repo...

AIMS: To compare different methods in order to assess adherence and persistence with oral endocrine therapy in women diagnosed with breast cancer (BC) in Catalonia. MATERIALS AND METHODS: This study covered all women newly diagnosed with stage I, II or IIIa BC and positive hormone receptors at six hospitals in Catalonia (Spain) in 2004. Adherence was assessed on the basis of physician report and patient self-report using a telephone questionnaire. Persistence was measured by refill prescriptions. We used the Kappa index to compare adherence measures and logistic regression to evaluate adherence-related risk factors. RESULTS: The study covered a total of 692 women. Adherence ranged from 92% (self-report) to 94.7% (physician report), depending on the measure used; persistence was 74.7% at 5 years of follow-up. Low concordance between measures was observed (Kappa range: 0.018-0.267). Patients aged 50-74 years showed higher adherence than those aged

Abstract #3151 Background: CT plus H is the standard treatment for HER2-positive MBC. Combination therapy of H plus vinorelbine is an active and safe regimen in this setting. The all-oral combination of NVBo and X has been reported as an active and safe regimen in many different trials in MBC. We report efficacy and safety information from an updated analysis of all 50 patients (pts) included in this trial, with a median follow-up of 28.5 months. Methods: Main eligibility criteria included: HER2-positive disease (defined as IHC 3+ or FISH+), documented measurable metastatic disease previously untreated by CT, relapse ≥ 6 months after the end of neoadjuvant or adjuvant CT, Karnofsky PS ≥ 70. NVBo was given as at a dose of 80 mg/m2 (after a first cycle at 60) D1 and D8 every 3 weeks, X at 1000 (750 if ≥ 65 years) mg/m2 bid D1-D14 every 3 weeks, H at 4 mg/kg on D1 as a loading dose then 2 mg/kg i.v. weekly starting on D8. Treatment was continued until progression. Results: Median age: 53.5years (18% ≥ 65); prior (neo)adjuvant CT 27 pts (54%); visceral involvement 41 pts (82%), > 2 metastatic sites 17 pts (34%); Median number of cycles: 10 (range 1-56); Median relative dose intensity: NVBo 75%, X 77%, H 96%; NVBo escalated to the recommended dose of 80 mg/m2 in 84% of pts; G3/4 NCI CTC v2 adverse events per pt: (n=49) neutropenia 69%, (n=50) febrile neutropenia 8%, infection without neutropenia 4%, stomatitis 4%, nausea 4%, vomiting 12%, diarrhea 16%, hand-foot syndrome 20%, asthenia 8%, LVEF decline 6%, alopecia (grade 2) 14%; Efficacy (n=44 evaluable patients): objective response rate (RECIST) 77% (95% CI [62-89]), CR 18%, PR 59%, SD 18%, PD 5%, disease control (CR+PR+ SD ≥6 months) 93% (95% CI [81-99]), median duration of response was 14.3 months (95% CI [9.8-16.8]), median progression-free survival was 12.8 months (95% CI [10.8-16.9]), overall survival results are not mature yet. Treatment is ongoing in 5 pts. Conclusion: The combination of NVBo and X + H has shown high antitumoral efficacy in pts with HER2-positive MBC. Toxicity profile was acceptable with, in particular, a very low rate of alopecia. An efficacy and safety analysis in pts aged < vs ≥ 65 years will be performed and presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3151.