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Goals of endocrine therapy for advanced breast cancer (ABC) include prolonging survival rates, maintaining the quality of life, and delaying the initiation of chemotherapy. We evaluated the effectiveness of fulvestrant as first-line in patients with estrogen receptor (ER)-positive ABC with relapse during or after adjuvant anti-estrogenic therapy in real-world settings. Retrospective, observational study involving 171 postmenopausal women with ER-positive ABC who received fulvestrant as first-line between January 2011 and May 2018 in Spanish hospitals. With a median follow-up of 31.4 months, the progression-free survival (PFS) with fulvestrant was 14.6 months. No differences were seen in the visceral metastatic (14.3 months) versus non-visceral (14.6 months) metastatic subgroup for PFS. Overall response rate and clinical benefit rate were 35.2% and 82.8%. Overall survival was 43.1 months. The duration of the clinical benefit was 19.2 months. Patients with ECOG performance status 0 at the start of treatment showed a significant greater clinical benefit rate and overall survival than with ECOG 1–2. Results in real-world settings are in concordance with randomized clinical trials. Fulvestrant continues to demonstrate clinical benefits in real-world settings and appears be well tolerated as first-line for the treatment of postmenopausal women with ER-positive ABC., Astra Zeneca Spain S.A., Madrid, Spain

Background In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab–paclitaxel in aTNBC. Patients and methods Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab–paclitaxel versus 5.7 months with placebo–paclitaxel]. In the PD-L1-positive population, atezolizumab–paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo–paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab–paclitaxel versus 28.3 months with placebo–paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov NCT03125902.

Background: Single-agent chemotherapy (CT) is the standard treatment option in endocrine receptor (ER)-positive advanced breast cancer (ABC) after failure of endocrine therapy (ET) or in patients (pts) without visceral crisis. Both weekly paclitaxel (WP) and oral vinorelbine (OV) are among the recommended treatment options in this setting. The aim of this study was to evaluate the efficacy and safety profiles of OV and WP in a face to face study. Material and methods: Pts with ER-positive, HER2-negative ABC, with an age ≥18 years and with a documented locally recurrent or metastatic involvement previously untreated by CT were eligible. Pts were randomized to receive, as first-line CT, 3 weekly-cycles of either: ARM A: weekly OV, given as a 80 mg/m2 dose (following a first cycle at 60 mg/m2, dose escalation to 80 in the absence of grade 3 or 4 toxicity at cycle 1); ARM B: WP 80 mg/m2 per week. Primary endpoint was disease control rate (DCR). Pts were stratified according to prior taxane CT and visceral metastases. Results: 131 pts have been treated (OV: 66, WP: 65). Baseline pts characteristics (Arms OV/WP): median age 58/61 years; median number of prior ET: 2/2; prior (neo) adjuvant CT 74/72%; prior anthracycline 67/62%; prior taxane: 41/42%; >3 metastatic sites 42/48%; visceral metastases 79/79%. Median number of cycles (range): 6(1-55)/7(1-44); dose escalation of OV was performed in 75% of pts. Safety: most common non-hematological related G3/4 adverse events per pt were fatigue 8/2%, peripheral neuropathy 0/5%, nausea 3/0%, diarrhoea 3/2%, vomiting 3/0%, constipation 3/2%, alopecia (G2) 2/34%, no toxic deaths; febrile neutropenia was present in 2/0% of pts. Quality of life: over time, no major differences between both arms have been observed. Efficacy: DCR in the intent-to-treat population was [95%CI] 75.8 [63.6-85.5] /75.4 [63.1-85.2]%; overall response rate 20/40%; median progression-free survival: 5.5/6.4 months. Median overall survival was: OV 27.6/WP 22.3 months. Conclusion: Both OV and WP reached similar DCR rates of 75%. Each regimen presented a specific tolerance profile, with, in particular, a lower incidence of alopecia and peripheral neuropathy with OV. OV and WP are valid first-line CT options for ER-positive/HER2-negative pts with ABC. Citation Format: Aapro MS, Hegg R, Ruiz Borrego M, Staroslawska E, Morales S, Cinieri S, De Freitas Junior R, Garcia Estevez L, Szombara E, Hervieu H, Groc M, Villanova GR. Final results of NorBreast-231, a randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel as first-line chemotherapy in patients with advanced breast cancer [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 P1-14-01.

Rationale: Quality of Life is of prime importance in Advanced Breast Cancer (ABC), a mostly non-curable disease. Both paclitaxel (P) and vinorelbine as single-agent chemotherapy (CT) are recommended treatment options in the management of ABC non-responsive to hormone therapy (HT) and with no visceral crisis. These agents are active with a good tolerance profile. The benefits and safety of oral vinorelbine (OV) and weekly P have however never been evaluated in a face to face trial. Methods: Main eligibility criteria included: age ≥18 years, documented locally recurrent or metastatic involvement previously untreated by CT, estrogen receptor positive disease previously treated by at least one HT, HER2-negative status, Karnofsky PS ≥70 and presence of at least one measurable lesion. Study treatment (until progression): Arm A, OV 80 mg/m2 weekly (following a first cycle at 60 mg/m2 and dose escalation to 80 in the absence of grade 3 or 4 toxicity); Arm B: paclitaxel 80 mg/m2 weekly. One cycle was defined as three weeks of treatment. Patients were stratified according to prior taxane (yes/no) and visceral metastases (yes/no). Primary endpoint was disease control rate (DCR), defined as confirmed complete response/partial response/stable disease of a minimum duration of 6 weeks. Results: 131 pts have been randomized (OV 66; P 65). Baseline patient characteristics (Arms A/B): median age 58/61 years; median number of previous HT 2/2; prior (neo)adjuvant CT 74/72%; prior anthracycline 64/62%; prior taxane 39/42%; >3 metastatic sites 42/48%; visceral metastases 80/78%. Safety: the most common non-haematological related G3/4 adverse events (≥3% patients) were: fatigue 7.6/1.5%, peripheral neuropathy 0/4.6%, nausea 3/0%, diarrhoea 3/1.5%, vomiting 3/0%, constipation 3/1.5%; alopecia (G2) was present in 1.5/33.8%; no toxic deaths observed. Efficacy: DCR in the intent-to-treat population was [95%CI] 75.8 [63.6-85.5]/75.4 [63.1-85.2] %; overall response was 20/40%; stable disease was 56/35% respectively. Treatment exposure, other efficacy / safety parameters and quality of life results will be presented during the meeting. Conclusion: Both OV and P reached similar DCR rates of 75%. As expected, each regimen presented a specific tolerance profile, with, in particular, a lower incidence of alopecia and peripheral neuropathy with OV. Citation Format: Aapro M, Ruiz Borrego M, Staroslawska E, Morales S, Cinieri S, De Freitas Junior R, Garcia Estevez L, Szombara E, Hervieu H, Groc M, Villanova G, Hegg R. Randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel in estrogen receptor positive, HER2-negative patients with advanced breast cancer (NorBreast-231 trial) [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 P6-14-03.

[Background]: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular., [Results]: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80., [Conclusions]: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method., M.M was supported by two research grants from Ministry of Economy and Competitiveness ISCIII-FIS grants (PI 12/02684): “Predictores genómicos de respuesta a la quimioterapia neoadyuvante con docetaxel-carboplatino en pacientes con cáncer de mama triple negativo”/“Genomic predictors of response to neoadjuvant chemotherapy with docetaxel-carboplatin in patients with triple negative breast cancer”; and (PI 15/00117): “Cáncer de mama triple negative: Predicción de respuesta a docetaxel-carboplatino neoadyuvante mediante caracterización de TILs y firmas inmunes basadas en secuenciación masiva de RNA”/” Triple negative breast cancer: Prediction of response to neoadjuvant docetaxel-carboplatin by characterization of TILs and immune signatures based on massive RNA sequencing”. C.M.P was supported by funds from the NCI Breast SPORE program (P50-CA58223).

Background Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. Patients and methods BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. Results As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Conclusions Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II.

Additional file 3. Treatments for bone metastasis per visit

Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0–1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients, This work was sponsored by GEICAM and Novartis. Roche funded the publication fees for this article

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Background Breast cancer in men is rare, assuming less than 1% of diagnosed breast cancer, requiring extrapolation of results from studies in women. Our objective is to evaluate prognostic and therapeutic factors paying special attention to the effect of hormonal treatment on the evolution of the disease. Methods Observational, retrospective, single-center study of 53 men with breast cancer treated between January 1997 and December 2018. The median follow-up was 66 months (range, 3-282 months). 48 patients had ECOG 0-1 (90.6%), 48 were hormone-receptor-positive (90.5%) and 4 HER2-positive (7.5%). 30 patients had lymph node involvement at diagnosis (56.6%). A total of 45 patients (84.9%) were treated with endocrine therapy (ET) of which 36 received it in adjuvant (67.9%) and 13 in metastatic phase (24.5%). 26 (49.1%) were treated with chemotherapy and 3 with cyclin-dependent kinase inhibitors (5.6%). The association analysis was performed using the Chi-square test and survival analysis with the Log-Rank test in SPSS v25. Results Our cohort had a median age of 68 years (range, 40-88 years). 84% had local or locally advanced stage. The infiltrative histologies were 88.7%. The BRCA gen test was carried out in 43.4%, which was positive in 26.1% of the analyzed patients, with BRCA2 being associated with lower mortality (p = 0.004). The statistic analysis showed greater 5-year overall survival (OS) and cancer-specific survival for ECOG 0-1 (p = 0.010, p = 0.048), absence of vascular invasion (p = 0.033, p = 0.025), Ki67 Conclusions The existence of prognostic factors already described in breast cancer in women also seem to be associated with men. The BRCA2 mutation could have a significant role as a predictive marker in males in the near future. ET helps reducing the risk of relapse, particularly at distance. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure F.J. Salvador Bofil: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis M. Ruiz Borrego: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly. All other authors have declared no conflicts of interest.

Background Approximately 40% of pts with HR+, HER2– ABC have mutations (mut) in PIK3CA, which encodes α-PI3K and leads to PI3K pathway hyperactivation and potentially ET resistance. ALP is a selective inhibitor of α-PI3K that, in combination with fulvestrant (FUL), significantly improved median progression-free survival (PFS) vs placebo + FUL in pts with PIK3CA-mut, HR+ HER2– ABC in the phase 3 SOLAR-1 trial (11.0 vs 5.7 mo, respectively; HR 0.65; 95% CI, 0.50-0.85; P Trial design BYLieve includes women (any menopausal status) and men with PIK3CA-mut, HR+, HER2– ABC and evidence of tumor progression on prior tx. Cohorts A and B comprise pts who received a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET as their last tx. With the adoption of Amendment 3, a new cohort (C) enrolls pts who had systemic chemotherapy or ET as last prior tx and who failed aromatase inhibitor (AI) in the adjuvant or metastatic setting. In the advanced setting, ≤2 anticancer tx (including ≤1 chemotherapy) are allowed. Pts must have ≥1 measurable lesion per RECIST criteria or ≥ 1 predominantly lytic bone lesion. Key exclusion criteria include prior PI3Ki tx and type 1 or uncontrolled type 2 diabetes. Study tx comprises: Cohort A (prior CDK 4/6i + AI), ALP 300 mg once daily (qd) + FUL 500 mg Q28d + C1d15; Cohort B (prior CDK 4/6i + FUL), ALP 300 mg qd + LET 2.5 mg qd; Cohort C, ALP 300 mg qd + FUL 500 mg Q28d + C1d15. The primary endpoint is the proportion of pts free of progression at 6 mo per local investigator assessment for each cohort. Secondary endpoints include PFS, PFS2, ORR, and CBR. Safety and tolerability will also be assessed, including fasted or random blood glucose levels (non-fasted). Tumor tissue and circulating tumor DNA are collected for biomarker assessments. The study is ongoing and currently recruiting pts, with increase in planned overall enrollment from 160 to 340 pts. Clinical trial identification NCT03056755. Editorial acknowledgement Medical editorial assistance was provided by Joe Hodgson of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure E. Ciruelos: Advisory / Consultancy, Speaker and consultant fee: Novartis, Roche, Pfzier, Lilly. T. Bachelot: Research grant / Funding (self), Research grant: Novartis; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Pfzier. S. Chia: Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Pfzier. D. Juric: Advisory / Consultancy, Scientific Advisory Board: Novartis, Genentech, Eisai, Ipsen, EMD Serono. N. Turner: Advisory / Consultancy: AstraZeneca, BMS, Lilly, MSD, Novartis, Pfizer, Roche/Genentech, Tesaro, Bicycle Therapeutics; Research grant / Funding (self): AstraZeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Guardant Health. A. Ridolfi: Full / Part-time employment: Novartis. N. Sophos: Full / Part-time employment: Novartis. B. Cooper: Full / Part-time employment: Novartis. A. Thuerigen: Full / Part-time employment: Novartis. H.S. Rugo: Research grant / Funding (institution): Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics and Macrogenics; Travel / Accommodation / Expenses: Lilly, Mylan, Pfizer, Amgen, Merck and Puma. All other authors have declared no conflicts of interest.

Background The combination of a CDK4/6 inhibitor (CDK4/6i) with letrozole (LET) or fulvestrant (FUL) is the most active first–line (1L) treatment for patients (pts) with HR[+]/HER2[-] ABC. Although endocrine sensitivity persists beyond progression, preliminary findings suggest more adaptive resistance mechanisms to endocrine therapy (ET) than to CDK4/6i. At present, there are no data about prolonging CDK4/6 blockade beyond progression on a CDK4/6i. The aim of this study is to determine whether palbociclib rechallenge combined with second–line ET upon progression to a prior palbociclib–based therapy will improve progression–free survival (PFS) over ET alone in HR[+]/HER2[-] ABC pts. Trial design This is an international, open–label, randomized phase II trial. A total of 198 pts will be randomized (2:1) to palbociclib plus ET (LET or FUL) or ET alone, until progressive disease (PD) or unacceptable toxicity. Pts will be stratified by 1L ET and presence of visceral metastasis. Main selection criteria include: (1) Pre– and post–menopausal women with HR[+]/HER2[-] ABC; (2) Evidence of PD on a 1L combination of palbociclib plus LET or FUL after obtaining clinical benefit (secondary resistance); (3) Pts relapsing on or within the first year of a palbociclib–based adjuvant regimen; (4) Measurable and biopsable disease or non–measurable disease with bone lesion. The primary objective is to assess PFS of palbociclib plus ET versus ET alone. The 1st co-primary endpoint is the PFS in the combination arm only. If this objective is achieved, we will compare PFS between the two arms (2nd co-primary endpoint). With 128 events, the 1st and 2nd analyses have an 80% power to detect a 1.4–month (hazard ratio [HR]=0.74) or 2.74–month (HR = 0.6) increase over 4–month median PFS for ET arm, respectively. The nominal alpha level is 5% for two-sided log-rank tests. Secondary objectives evaluate: Safety–related outcomes, objective response rate, 6–month clinical benefit rate, overall survival, quality of life, and time to first chemotherapy. Exploratory objectives include: Correlation between the intrinsic molecular subtypes and efficacy/safety findings, and identification of new predictive markers. Clinical trial identification NCT03809988. First Posted: January 18, 2019. Legal entity responsible for the study Medica Scientia Innovation Research (MedSIR). Funding Pfizer S.L.U. Disclosure A. Llombart Cussac: Honoraria (institution), Advisory / Consultancy: Roche, GlaxoSmithKline, Novartis, Celgene, Eisai, AstraZeneca; Research grant / Funding (institution): GlaxoSmithKline, Sanofi, Puma Biotechnology; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). P. Schmid: Advisory / Consultancy: Pfizer, AstraZeneca, Novartis, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, Puma; Research grant / Funding (institution): AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas; Spouse / Financial dependant, Spouse is consulting for Genentech/Roche: Genentech/Roche. I. Macpherson: Honoraria (self): Celldex, Daiichi Sankyo, Eisai, Genomic Health, Novartis, Pfizer, Roche; Travel / Accommodation / Expenses: Eisai, Roche. J. Gligorov: Advisory / Consultancy: Daichi, EISAI, Genomic Health, Ipsen, Macrogenics, MSD, Novartis, Onxeo, Pfizer, Roche Genentech; Travel / Accommodation / Expenses: EISAI, Genomic Health, MSD, Novartis, Pfizer, Roche Genentech; Non-remunerated activity/ies: Daichi, EISAI, Genomic Health, Immunomedics, Novartis, Pfizer, Roche Genentech. M. Sampayo: Full / Part-time employment: Medica Scientia Innovation Research (MedSIR). F. Riva: Full / Part-time employment: Medica Scientia Innovation Research (MedSIR). A. Malfettone: Full / Part-time employment: Medica Scientia Innovation Research (MedSIR). J.M. Perez-Garcia: Advisory / Consultancy: Roche, Lilly; Full / Part-time employment: Medica Scientia Innovation Research (MedSIR). J. Cortes: Advisory / Consultancy: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex; Honoraria (institution): Roche, Novartis, Celgene, Eisai, Pfizer, Samsung; Research grant / Funding (institution): Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck SharpD Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Medica Scientia Innovation Research (MedSIR). All other authors have declared no conflicts of interest.

Aggressive non-Hodgkin's lymphomas (NHL) in localized stages I and II, without bulky areas and a fair International Prognostic Factor (IPI) (30% of all cases) have high possibilities of cure (80%) when treated with combined chemotherapy, CHOP or CHOP-like (3-4 courses) followed by locoregional radiation therapy. Localized aggressive non-Hodgkin's lymphomas with signs of poor prognosis or advanced stages (III and IV) must be treated with rituximab-containing immunochemotherapy. As second line in responding patients (DHAP, ESHAP, MINE, VIM, DICE, etc., and rituximab) high doses chemotherapy with hematopoietic growth factor support should be considered, although not in refractory patients.

Background The aim of this paper is to analyse breast cancer mortality in Andalucia (Spain) between 1975 and 1999 based on age–period–cohort. Patients and methods Mortality data were obtained from the Mortality Registry of Andalucia. Deaths and population were divided into 13 age groups and five 5-year periods. From this, age-specific mortality rates for 17 birth cohorts were computed. These were plotted and fitted to Poisson regression models to assess age, period and cohort effects. Results The best fit was found for the complete model, which simultaneously considered the effects of age–period–cohort. Cohort effects were found to be more important than period effects in terms of model fit. Conclusion These effects were manifest as a seemingly consistent increase in the relative risk of breast cancer mortality with a three-fold increase in women born in the 1950s relative to those born in the 1890s.

Aggressive non-Hodgkin's lymphomas (NHL) in localized stages I and II, without bulky areas and a fair International Prognostic Factor (IPI) (30% of all cases) have high possibilities of cure (80%) when treated with combined chemotherapy, CHOP or CHOP-like (3-4 courses) followed by locoregional radiation therapy. Localized aggressive non-Hodgkin's lymphomas with signs of poor prognosis or advanced stages (III and IV) must be treated with rituximab-containing immunochemotherapy. As second line in responding patients (DHAP, ESHAP, MINE, VIM, DICE, etc., and rituximab) high doses chemotherapy with hematopoietic growth factor support should be considered, although not in refractory patients.

Background: Resistance to targeted-therapies is a current problem in our clinical practice. In HER2 overexpressing tumors, resistance to trastuzumab-based therapies is widely observed. Expression of SRC has been pre-clinically linked to trastuzumab resistance and the addition of the multi-tyrosine kinase inhibitor dasatinib to trastuzumab increases its antitumor activity (Seoane S, et al. J Natl Cancer Inst. 2010). On previous studies, Dasatinib showed a good toxicity profile, with low grade 3-4 toxicity rates (E. Mayer, et al. J Clin Oncol 2009). We have designed a phase I-II trial combining dasatinib with standard trastuzumab/paclitaxel. (ClinicalTrials.gov Identifier: NCT01306942). In this abstract we report the description of the phase II part of the trial which is ongoing. Trial Design: Eligible patients must be HER2+ (evaluated by central laboratory and assessed by immunohistochemistry and fluorescent in-situ hybridization) MBC and candidates for trastuzumab + chemotherapy as first line treatment. Taxanes and trastuzumab administered in the adjuvant setting are permitted if given >12 months before the inclusion. Patients with CNS involvement are eligible if treated and clinically stable without medication. Treatment consists of trastuzumab 2 mg/kg weekly (following a loading dose of 4 mg/kg in cycle 1), weekly paclitaxel (80 mg/m2, 3 weeks on-one week off) and dasatinib 100 mg once daily (based on the recommended phase II dose from the phase I part, Gil-Martin M, et al. European Breast Cancer Conference 2014, P-041) in a 28-days cycle. Patients are treated until radiologic or symptomatic progression or unacceptable toxicity. The primary objective for this phase II is efficacy, measured by Objective Response Rate (ORR according to RECIST 1.1). Secondary objectives are: Safety (evaluated using NCI-CTCAE v 4.03), Clinical Benefit Rate, Time to Progression, Progression Free Survival and Response Duration. Pharmacodynamic biomarkers include pAKT, pS6, pSRC, pErk1/2 in tumor tissue samples, mononuclear cells in blood samples and in skin tissue. An additional exploratory objective is to evaluate the correlation between the early presence of lymphocytosis and efficacy. The study will be considered positive if ORR increases 25% from a 50% ORR observed in previous studies with paclitaxel + trastuzumab. We need to include 28 evaluable patients to demonstrate this hypothesis (with an alpha error of 0.05 and a statistical power of 80%), assuming a 10% drop-out rate. Twenty one patients have already been included. Recruitment is expected to finish by the end of 2015. Citation Format: Ocaña A, Ruiz Borrego M, Gil-Martín M, Antolín S, Guerrero Á, Vidal Boixader L, Martín M, Trigo Pérez JM, Rojo F, Jerez Y, Atienza M, Pernas S, Hernando A, Carrasco E, Benito S, Caballero R, Pandiella A. A phase I-II trial of dasatinib in combination with trastuzumab (T) and paclitaxel in the first line treatment of HER2 positive metastatic breast cancer (MBC) patients: GEICAM/2010-04. [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 OT3-01-02.

Background: Chemotherapy (CT) is widely used in the management of estrogen receptor (ER) positive breast cancer patients (pts) pre-treated by hormone therapy (HT) . Single-agent CT in this setting has been validated in guidelines of management of the disease. Both paclitaxel and vinorelbine are recommended among the standard available CT agents for advanced breast cancer (ABC). Weekly paclitaxel (P) and oral vinorelbine (OV) as single agents are active with a good tolerance profile for these pts. Oral CT offers significant advantages over intravenous CT because of its greatest convenience, its ease of administration and reduced need for hospitalisation. Since the benefits and safety profile of OV and weekly P have never been compared in a face to face trial, this study will provide key clinical data regarding the optimal management of this patient population: ER positive and HER2-negative disease previously treated by a HT. Trial design: In this open-label study, pts are randomized to receive: OV 60 mg/m2/week (day 1, 8, 15) for the first cycle, then increased to 80 mg/m2/week from the second cycle in the absence of grade 3 or 4 toxicity or weekly P 80 mg/m2/week (day 1, 8, 15) intravenously. Treatments are continued until disease progression, unacceptable toxicity or pt's refusal. Main eligibility criteria include: age ≥18 years, documented locally recurrent or metastatic disease previously untreated by CT, ER positive disease previously treated by at least one HT, HER2-negative disease, Karnofsky PS ≥70. Primary objective: disease-control rate (defined as objective response or stable disease for a minimum of 6 weeks). Secondary objectives: other efficacy parameters, evaluation of safety profiles of both arms and quality of life assessment. Statistical methods: the one-sample multiple testing procedure for phase II clinical trials described by Fleming is used. This procedure employs the standard single stage test procedure at the last one of 2 pre-specified testings, while both allowing for early termination (should extreme results be seen) and essentially preserving the size and power of the single stage procedure. 124 pts will be enrolled in this randomized phase II study (62 per treatment arm). Randomisation is stratified according to prior taxane (yes or no) and presence of visceral metastases (yes or no). Disclosure: M. Aapro: Advisory Board Member, Pierre Fabre; M. Morand: Employee of Pierre Fabre Medicament; G.R. Villanova: Employee of Pierre Fabre Medicament. All other authors have declared no conflicts of interest.

We report a case of primary endobronchial non-Hodgkin Lymphoma, an unusual extranodal lymphoma, in a 62 year old patient, which begins with malaise, marked respiratory symptoms and empyema. We especially discuss its diagnostic's criteria and its clinicoradiologic manifestations. We argue over its pathologic, immunohistochemical and cytogenetic features according to the REAL classification of lymphomas. On previous experience and the good response of this case, we propose chemotherapy followed radiotherapy may would be a suitable therapeutic approach.

Metastatic infiltration of the liver is an uncommon cause of acute hepatic failure. We describe the case of a 55-yr-old man who presented with signs and symptoms of liver disease. Diagnostic testing revealed a small cell carcinoma of the lung with massive hepatic metastases.