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Purpose Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting. Methods We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described. Results The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%). Conclusions This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.

ObjectiveTo evaluate the efficacy of clinical triage of oncological patients for safe continuation of cancer therapy implemented during the first SARS-CoV-2 outbreak.MethodsBetween 25 February and 21 April 2020, patients attending the Medical Oncology Unit, Spedali Civili Hospital, Brescia (Italy) for cancer therapy underwent triage to identify those with no signs and symptoms suspicious for SARS-CoV-2 infection in which antineoplastic treatment could be continued as scheduled. Triage questions investigated common symptoms (e.g., fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhea, nausea and vomiting); body temperature and pulse oximetry were also recorded. All patients were followed-up for overt SARS-CoV-2 through to 18th May 2020.ResultsOverall, 1180 patients (median age 65 years) underwent triage during the study period. The most frequent primary malignances were breast (32%), gastrointestinal (18%), and lung (16.5%) cancer. Thirty-one (2.5%) presented with clinically evident SARS-CoV-2 infection and tested positive on nasopharyngeal swab testing and/or radiological imaging. Triage identified 69 (6%) grey zone patients with symptoms suspicious for SARS-CoV-2; 5 (7.2%) subsequently developed symptomatic disease. Neither the symptomatic nor the grey zone patients received their scheduled treatment; instead, they were referred for hospitalization or home quarantine.ConclusionTriage of oncological patients at our Unit provided for safe continuation of scheduled cancer treatment in 91.5% of patients during the initial SARS-CoV-2 outbreak.

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2–3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt “healthier dietary patterns” during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.

Purpose: The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor—positive (HR+), HER2-negative (HER2−), advanced breast cancer (HR+/HER2− aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus. Experimental Design: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2− aBC treated with everolimus-exemestane. Results: We evaluated 809 patients with HR+/HER2− aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15–2.69; P = 0.008). Conclusions: The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2− aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2− aBC.

Background The DigniCap System is an effective scalp cooling device for the prevention of chemotherapy-induced alopecia in early breast cancer patients. Aim This prospective study was designed to confirm the efficacy and tolerability of the device, to explore potential factors associated with its efficacy and to collect data on patient perceptions and satisfaction. Methods Between January 2016 and June 2018, 163 early breast cancer patients eligible for adjuvant chemotherapy were enrolled. Hair loss was assessed using the Dean scale, where a score of 0-2 (hair loss ≤50%) was defined as successful. Results Hair preservation was successful in 57% of patients in the overall series. The proportion was even higher (81%) in the patient subgroup treated with a paclitaxel and trastuzumab regimen. Side effects (feeling cold, headache, head heaviness, scalp and cervical pain) were mild to moderate and did not correlate with the rate of hair loss. Lifestyle, anthropometric factors and hair characteristics failed to be associated with device efficacy. Conclusions The DigniCap System was well tolerated and found to be effective in preventing alopecia in early breast cancer patients. Our study failed to identify factors other than type of chemotherapy regimen associated with hair preservation.

Background: During the SARS-COV-2 pandemic, cancer patients (pts) who are infected may develop severe disease if their systemic treatment is not temporarily stopped Nasopharyngeal swab was not extensively available to screen cancer pts for SARS-COV-2 infection in northern Italy, the most area in the country most affected by the pandemic From the beginning of the outbreak onwards, all pts admitted to the Medical Oncology Unit at Spedali Civili Hospital, Brescia, underwent a triage investigating the presence of symptoms and signs suggestive of SARS-COV-2 infection Triage results were used to decide which pts should continue antineoplastic treatments Methods: All consecutive cancer pts being admitted for systemic treatment from February 24th to April 21st 2020 were considered Triage, performed by a trained nurse, consisted of questions regarding the presence of fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhoea, nausea and vomiting, measurement of body temperature and pulse oximetry All enrolled pts were followed-up for overt SARS-COV-2 development until May 18th Results: Overall, 1180 pts were included, 54% female and median age 65 years Most represented primary malignancies were breast (32%), gastroenteric (18%) and lung (16 5%) Thirty-one (2 5%) presented with clinically evident SARS-COV-2 disease and infection was proven by positive nasopharyngeal swab and/or radiological imaging The triage identified 69 (6%) “grey zone” pts, with suspicious symptoms (i e fever 41%, cough 30%, dyspnea 19%) The nasopharyngeal swab was negative in 48% of them and was not performed in the remaining 52% of pts, as well as in all pts who were triage negative Both SARS-COV-2 positive and “grey zone” pts did not receive treatment and were addressed to hospitalisation or home quarantine All the 1080 pts (91 5%) who resulted negative at triage continued their antineoplastic therapy as scheduled, none of them presenting symptoms of SARS-COV-2 infection during the follow-up Conclusions: Accurate triage allowed safe continuation of anticancer treatment in 91 5% of pts during the SARS-COV-2 outbreak Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Patients with cancer are at a higher risk of developing serious disease-related complications in case of contracting SARS-CoV-2. Oncology units should implement all possible preventive measures to reduce the risk of viral transmission by healthcare professionals (HCPs) to patients. We conducted a surveillance for SARS-CoV-2 infection among the staff members of the Medical Oncology Unit of ASST Spedali Civili in Brescia, one of the Italian areas most affected by the SARS-CoV-2 pandemic. The aim of this study was to demonstrate whether the recommended preventive measures, promptly implemented by the unit, have been effective in reducing the spread of the virus among the HCPs. Between February 24 and May 19, 2020, SARS-CoV-2 infection was detected in 10 out of 76 healthy HCPs (13%). Six of them developed a symptomatic disease, leading to home quarantine, and four remained asymptomatic. The infection was revealed when a serology test was performed on all staff members of the unit. In seven HCPs, in which it was possible to trace the person-to-person infection, the contagion occurred as a result of unprotected contacts or partially protected with surgical masks. In particular, four asymptomatic HCPs did not stop working, but a widespread outbreak in the unit was avoided. Adherence to the recommended preventive strategies, in particular, wearing of surgical masks by both the HCPs and the patients, is effective in reducing and preventing the viral spread.

Background Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. Methods EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Results After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9–8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2–9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2–3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2–3 arm A vs B, 19% and 38%, respectively). Conclusion Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. Trial registration EudraCT, 2012-002707-18. Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222. Retrospectively registered on May 26, 2016.

Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3–4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3–4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.

Aromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High‐fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI‐naïve or AI‐treated. A total of 684 consecutive breast cancer patients were enrolled in this cross‐sectional study. Each woman underwent a dual‐energy X‐ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI‐naïve and 240 AI‐treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy (p = .0311). Among AI‐treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high‐LBM and low‐FBM group, 23.2% in high‐LBM and high‐FBM group, and 19.8% in low‐LBM and low‐FBM group). Among AI‐naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Background: W taxanes (T) are commonly used in the treatment of older BC pts, with neurotoxicity (NTX) and fatigue being dose-limiting toxicities with a possible negative impact on function. No prospective data exists on the safety and efficacy of W NP in this population. NP might be of particular value in older pts, due to no need for premedication with steroids and shorter time to recovery from neurotoxicity than conventional T, resulting in a reduced risk of exacerbation of comorbidities such as hypertension and diabetes, and possibly of functional decline (FD). Methods: Pts aged ≥ 65 years (y) with Her-2 negative or Her-2 positive (+), but contraindicated to anti-Her-2 therapy, advanced BC were randomized to receive NP as first-line chemotherapy at either 100 (Arm A) or 125 mg/m2 (Arm B), days 1, 8, 15 q 28. The primary end-point was event-free survival (EFS). An event was either disease progression (PD), death, or FD - defined as a decrease of at least 1 point from baseline values of activities of daily living (ADL) or instrumental ADL (IADL), deemed by the investigator as treatment-related and confirmed at the subsequent cycle. Secondary endpoints included progression-free survival (PFS), response rate (RR) in pts with measurable disease, and incidence of adverse events (AEs). Results: From January 2013 to September 2016, 160 pts were randomized in 15 Italian centres; all but 2 who never started NP were eligible for final analysis. Pts median age was 72y (range 65-84) in Arm A and 73y (range 65-88) in Arm B. Median ECOG performance status was 0 (range 0-2). Baseline IADL impairment was reported in 20 pts (25%) in both arms. >80% pts had ER+ tumors; 2 pts had HER2+ disease. Visceral disease was present in 71% (Arm A) and 70% (Arm B) of pts. Prior exposure to T in the neo/adjuvant setting was 14% (Arm A) and 13% (Arm B). Median number of delivered cycles of NP was 6 (range 1-28 in Arm A, and 1-22 in Arm B), with 3 pts still on treatment. Dose reductions were similarly reported (72% of pts Arm A, 78% of pts Arm B). At a median follow-up of 21 months (mos) (Interquartile range 14-28.4) 140 events were observed. Arm A/Arm B: PD n=53(67%)/n=52(66%); FD n=13(15%)/n=14(18%), death n=3(4%)n=5(6%). Outcomes data are reported in the following table: Outcomes Arm AArm BMedian EFS, mos (90% CI)6.2 (5.5-8.4)6.4 (5.8-7.7)Median PFS, mos (95% CI)8.3 (5.9-10.5)8.8 (7.4-10.3)RR (95% CI)37% (25-50)42% (30-54) Fatigue (Arm A: grade (G)2 29%, G3 11%; Arm B: G2 46%, G3 5%) and NTX (Arm A: G2 15%, G3 4%; Arm B: G2 28%, G3 8%) were the most frequently reported AEs. No G4 AEs were reported with the exception of neutropenia (1 pt in arm A) and leucopenia (3 pts in Arm A, 1 pt in arm B). 1 G5 (sepsis) was recorded in Arm B. NTX was reported as the reason for treatment discontinuation in 21 pts (13%) of whom 16 (21%) in arm B. Conclusion: Looking at classical study endpoints (PFS, RR), both doses of NP are active in older pts. However, 17% of pts had to stop treatment due to FD, assessed according to predefined criteria. Due to similar efficacy and reduced NTX, W NP 100 is the suggested dose to be used in older pts with advanced BC. Citation Format: Biganzoli L, Berardi R, Pedersini R, Minisini AM, Caremoli ER, Spazzapan S, Lima JS, Baldari D, Orlando L, Magnolfi E, Pistelli M, Brunello A, Zafarana E, Bernardo A, Leo S, Colleoni M, Donati S, De Placido S, Parolin V, Vitale S, Di Leo A, Puglisi F, Boni L, Cinieri S. The effect trial: A randomized phase II trial evaluating two different doses of weekly (W) NAB-paclitaxel (NP) as first-line chemotherapy in older breast cancer (BC) patients (pts) [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 P6-14-01.

Background: Alopecia is a common and distressing adverse effect in breast cancer (BC) patients (pts) receiving adjuvant chemotherapy. The aim of the study was to assess the effectiveness and safety of this device to prevent chemotherapy-induced alopecia in early breast cancer patients (EBCP) receiving adjuvant treatment. The quality of life of pts was also evaluated. Patients and methods: From January to December 2016, a sensor-controlled scalp cooling system (DigniCap:Sysmex Europe GmbH, Norderstedt, Germany) was proposed to a consecutive group of EBCP submitted to adjuvant chemotherapy at the Breast Unit of Spedali Civili Hospital of Brescia. Degree of hair loss was assessed by two nurse using Dean's alopecia scale by digital photographs at baseline and each chemotherapy cycle. EORTC QLQ-C30 questionnaire and self-reported visual analogical scale (VAS) of symptoms (anxiety, tone of mood, fatigue, nausea,well-being, activity) were collected at baseline and after the first two cycles of chemotherapy. Results: 70 pts were enrolled and 49 (70%) completed the chemotherapy plan and were evaluable. Median age was 51 years, 8 pts (16%) received neoadjuvant and 41 pts (84%) adjuvant chemotherapy, 21 (43%) were treated with 4 cycle of chemotherapy (TC, EC or paclitaxel alone), and 28 (57%) with sequential chemotherapy with antracycline and taxane +- trastuzumab. Fifteen pts (30%) stopped the treatment because of loss of hair in 9 pts, for headache in 4 pts and for other problems in 2 pts. At the end of chemotherapy, 13 pts (27%) had no loss of hair (Dean score 0), 25 pts (51%) had a minimal loss of hair (Dean score 1), 9 pts (18%) had a 50% hair loss (Dean score 2), 2 pts (4%) had a 75% hair loss (Dean score 3). No pts reported hair loss more than 75% (Dean score 4). There wasn't a significant difference between mean score value of QLQ-C30 at baseline and after chemotherapy and between the groups with and without hair loss. VAS documented an increase of fatigue and decrease of anxiety from baseline to final evaluation. The side effects presented with the use of DigniCap were the following: headache in 32% of pts and cold feeling in 57 % of pts. Conclusion: Scalp cooling with cold caps appears to be effective in preventing CIA among the majority of women undergoing treatment chemotherapy. The quality of life did not change in scalp-cooled patients. Acknowledgments: a thank you to the ESA association that donated Dignicap to Oncology Department. Citation Format: Vassalli L, Pedersini R, Romelli M, Claps M, Fornaro C, Conti E, Tagliani M, Baronchelli A, Ragni D, Lombardi E, Rodella F, Amoroso V, Berruti A, Simoncini EL. Efficacy and patient acceptability of the DigniCaP ScalpCooler to prevent hair loss in breast cancer patients receiving adjuvant chemotherapy [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 P6-11-19.

Background: Dysgeusia is a frequent side effect in breast cancer patients undergoing adjuvant chemotherapy. The effect of dysgeusia on changes in diet and patient weight has been poorly investigated. We evaluated prospectively dysgeusia in a consecutive series of early breast cancer patients (EBCP) with the aim to explore its impact on food selection and weight changes. Patients and methods: From May 2014 to April 2017, 130 consecutive EBCP were enrolled at the Oncology and Breast Units at Spedali Civili in Brescia. Dysgeusia was categorized as present or absent, changes in types and frequencies of food consumptions during chemotherapy were assessed by a specific questionnaire and photography atlas. Evaluations were performed at baseline, after 3 cycles, at the end of chemotherapy plan and during follow-up. Results: all 130 pts were evaluable. Median age was 53 years (range 26-76), median weight 64 Kg (range 45-115), median BMI 23,86 Kg/m2 (range 17,01-35,49), 73 pts (56%) performed physical activity, 57 pts (44%) were abstemious, 22 pts (17%) received neoadjuvant and 108 pts (83%) adjuvant chemotherapy, 25 pts (19%) were treated with antracycline based schemes, 83 (64%) with antracycline and taxane plus or minus trastuzumab, and 22 pts (17%) other regimens. Seventy-three per cent of pts developed dysgeusia during chemotherapy (p=< 0.001), and in 19% this side effect persisted three months after chemotherapy. Dysgeusia was associated with the length of chemotherapy treatment and taxane use. A statistically significant increase of taste alteration was reported for all metallic, sweet, bitter, salted and acid taste (p Conclusion: Dysgeusia was frequent in EBCP undergoing adjuvant chemotherapy. It directly correlated with fatigue and meteorism and inversely correlated with mucositis. This adverse event had no impact on weight and BMI but significantly influenced food intake with a preference of glucose containing instead of fat containing foods. Acknowledgments: a thank you to Beretta foundation for the costant support to Breast Unit and Oncology Department. Citation Format: Pedersini R, Zanini A, Romelli M, Coccoli V, Guerra M, Bosio S, Schivardi G, Rodella F, Vassalli L, Amoroso V, Claps M, Simoncini EL, Berruti A. Dysgeusia, weight and eating habits changes in breast cancer patients undergoing chemotherapy: A prospective cohort study [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 P6-11-16.

Nab-P is widely used in MBC, but limited data from clinical practice are available. This is an open-label, multicentre prospective cohort study prospectively collecting data of MBC pts treated with weekly, or every 3 week administration of Nab-P. For this survey a convenience sample was used. An attempt was made to get at least a sample of 200 pts, which guarantees a standard error of 3.5% for estimation of survival time at 1 year, overall response rate and grade 3-4 toxicity. Overall response rate was 32.1% in the whole population, without any significant difference according to schedule, previous paclitaxel exposure, presence of visceral metastases or line of treatment. Median time to progression was 6 months (95% confidence interval, 1-34), with no differences according to the schedule of treatment. No new data on toxicity were reported. Results from this real life experience suggest that Nab-P can be safely used with both the weekly and the 3-weekly schedule with comparable efficacy, leaving the choice to the physician according to the patient's needs and preference, with a carefully balance between activity and potential toxicity. Background Few data are available regarding efficacy and safety of nanoparticle albumin-bound (nab)-paclitaxel in advanced breast cancer patients outside a controlled trial, especially for the weekly schedule. Patients and Methods We prospectively collected data of advanced breast cancer patients who were candidates to be treated with weekly (125 mg/m2 for 3 consecutive weeks followed by a 1-week rest) or every 3 weeks (260 mg/m2) schedules of nab-paclitaxel, according to physician's decision. Results The study enrolled 209 patients, of whom 92 (39.3%) received weekly nab-paclitaxel. The median age was 58 (range, 31-84) years; 21.8% of the patients were classified as triple-negative breast cancer (estrogen-recetor/progesteron-receptor-negative). The median number of cycles was 5.5. The overall response rate was 32.1% in the whole population, without any significant difference according to schedule, previous paclitaxel exposure, presence of visceral metastases, or line of treatment. The median time to disease progression was 6 months (95% confidence interval, 1-34), with no differences according to the schedule of treatment. Severe adverse events (Grade 3-4) were observed in 60.6% of the patients. The main toxicities were alopecia (53.4%), neutropenia (3%), and sensory neuropathy (2.1%). Conclusion Our real-life data indicate that both schedules of nab-paclitaxel are manageable and safe in advanced breast cancer patients, even if previously treated with other taxanes.

INTRODUCTION Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with sunitinib in this setting published to date and summarized it in a meta-analysis. EVIDENCE ACQUISITION Patients with GBM recurrent or progressive after surgery and standard chemo-radiotherapy were treated with sunitinib 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon's two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib. EVIDENCE SYNTHESIS Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-PFS was not reached. Therefore, the trial was stopped early for insufficient activity. All toxicities were grade 1-2. Systematic review of the literature identified 9 studies (including the present one) for a total of 221 patients. Pooled 6-PFS was 15.1% (95% CI: 9.0-24.4). Subgroup analysis by different schedule revealed a 6-PFS of 17.5% (95% CI: 10.3-28.1) in the weekly setting which was consistent across all the studies (I2=0%, P=0.66) and a pooled 6-PFS of 12.7% (95% CI: 4.9-29.1) in the daily setting with a substantial amount of heterogeneity (I2=65%, P=0.01). CONCLUSIONS Results of this trial and those of the systematic review indicate that, compared to conventional chemotherapy or bevacizumab, sunitinib has insufficient activity in the setting of recurrent GBM. Better patient's molecular stratification for second-line treatment in GBM is warranted.

Several trials have demonstrated the benefit of anti-CDK4/6 inhibitors plus endocrine therapy in estrogen receptor-positive (ER+) advanced breast cancer (BC), in first or subsequent lines of therapy. However, due to the lack of direct/indirect comparisons, there are no data demonstrating the superiority of one drug over the other. We compared the effectiveness of palbociclib, ribociclib, and abemaciclib in advanced ER + BC via an indirect adjusted analysis. We performed electronic searches in the PubMed, EMBASE, and Cochrane databases for prospective phase 3 randomized trials evaluating anti-CDK4/6 inhibitors plus endocrine agents. We compared the results with an adjusted indirect analysis of randomized-controlled trials. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR) and G3–4 toxicities occurring in ≥ 5% of patients. Six trials and six treatment arms including a total of 3743 participants, were included. For PFS and ORR analysis, the three agents were similar in both first- and second-line studies. All G3–4 toxicities were similar, with reduced risk of diarrhea for palbociclib versus abemaciclib (relative risk [RR] 0.13, 95% CI 0.02–0.92; P = 0.04) and of QTc prolongation for palbociclib versus ribociclib (RR 0.02, 95% CI 0–0.83; P = 0.03). Despite different inclusion criteria and length of follow-up, similar features were noticed among second-line studies with the exception of increased risk of anemia G3–4 and diarrhea G3–4 for abemaciclib. Based on PFS and ORR results of this indirect meta-analysis, palbociclib, ribociclib, and abemaciclib are equally effective in either first- or second-line therapy for advanced ER + BC. They, however, ported different toxicity profiles.

Objectives: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting. Methods: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m2 on days 1 and 8 every 21 days. Results: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE. Conclusions: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.

Objectives To describe the prevalence, severity, and self-reported characteristics of taste alterations (TAs) induced by chemotherapy and to investigate TAs across chemotherapy regimens. Sample & setting 243 adult patients from five outpatient practices in Northern Italy. Methods & variables Correlation, univariate, and multivariate linear regression analyses. Variables include TAs, symptoms reported by patients, and the effect of TAs on quality of life. Results A majority of the study sample reported TAs. Difficulty in tasting saltiness was most common, followed by difficulty in tasting umami and sweetness. The severity and characteristics of TAs changed across chemotherapy regimens. TAs correlated with quality of life and were significantly associated with patient's age and a 21-day chemotherapy schedule. Implications for nursing TAs are a frequent side effect of chemotherapy, with varying characteristics that have a negative effect on quality of life. Healthcare professionals should routinely assess for TAs and provide patients with specific management strategies depending on the nature of TAs.

Introduction: Circulating Tumor Cells (CTCs) levels are dynamic indicators of prognosis and response to therapy in metastatic breast cancer (MBC) patients (pts). CTCs levels have been reported to be higher in pts with bone than visceral metastases, respectively. However, little is known about CTCs levels in pts with BM involvement. We analysed CTC patterns in patients with either visceral, bone or BM to test the hypothesis that BM involvement would facilitate tumor cells to enter the systemic circulation as CTCs. Patients and methods: Sites and extension of metastatic disease were identified with conventional imaging. Bone metastases were diagnosed with either bone scintigraphy or CT-PET and the BM involvement was documented histologically by BM biopsy and metabolically by CT-PET. A training set of 10 pts was evaluated by both BM biopsy and CT-PET to verify the diagnostic performance of CT-PET in identifying BM metastases (M+). We found a 100% concordance between BM biopsy and CT-PET and we therefore used CT-PET for further analyses. The CellSearch System (Veridex LLC, Raritan, NJ, USA) was used for the isolation and enumeration of CTCs in peripheral blood. The Student's t-test and the two-way ANOVA test were used to compare means of CTCs among patients with different metastatic patterns. Results: The CTCs mean and median scores of 129 MBC pts were analysed. Final analysis focused on 101 pts with bone M+. Thirty-three pts had bone M+ alone and 68 pts had bone and visceral M+ (including lymphnodes, brain, liver and lung/pleura). Number of metastatic sites was 1, 2, 3, 4, 5 in 30%, 37%, 25%, 6% and 2% of pts, respectively. BM involvement was documented in 27 (27%) of pts in the whole series and in 12 (33%) of pts with bone M+ alone. Mean CTCs score in the whole series was 392 (0-9993) and the median number of CTCs was 20. In the whole series, BM involvement was associated with higher mean CTCs scores (1350 vs 42, p .014). In pts with bone M+ alone, mean CTCs score was 696 (0-7000) and pts with BM involvement had higher mean CTCs scores (1846 vs 39, p 0.37). Among the different metastatic patterns, the association of bone with BM involvement and liver M+ was correlated with the highest CTCs numbers. We could not perform comparisons in the 68 pts with both bone and visceral localizations because of the variety of metastatic patterns. However, the two-way ANOVA showed a significant influence of BM involvement on mean CTCs scores in pts with different metastatic patterns (p >.001). Conclusions: This work confirms that pts with bone metastases have higher numbers of CTCs than pts with visceral metastases. Extensive bone disease with BM involvement is characterized by an increase in CTCs numbers compared to bone disease without BM involvement. Bone marrow metastases are metabolically more active by CT-PET and can be accurately detected by metabolic imaging without need of BM biopsy. Further studies are ongoing. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-19.

e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase the risk of clinical fractures but the mechanism underlying the increased fracture risk (FR) is not...

Aims and Background Advanced chemorefractory epithelial thymic tumors are still a challenge in clinical oncology. A therapeutic approach targeting a key molecular pathway could be the ideal solution in a neoplasm that can overexpress epidermal growth factor receptor (EGFR) in the epithelial component. Methods A patient with metastatic heavily pretreated thymic carcinoma was evaluated for EGFR expression in the primary tumor. Results Strong EGFR expression was revealed by immunohistochemistry. The patient received erlotinib therapy but had obtained no response after four months of treatment. Conclusion This preliminary experience suggests that erlotinib may not be a useful therapeutic choice in advanced pretreated thymic carcinomas.

Salivary gland carcinomas are rare cancers, comprising 1-5% of head and neck cancers. They represent a morphologically and clinically diverse group of tumors. The most commonly histopathologic types are mucoepidermoid cancer, adenoid cystic cancer and adenocarcinomas. Malignant salivary gland tumors generally present as painless, slow-growing tumors that are indistinguishable from benign tumors. Surgery is the principal treatment and is curative in early stage. Radiation therapy should be considered in most patients after surgical resection. Chemotherapy is reserved for palliative treatment of metastatic disease but results are disappointing. Recent studies have investigated the role of targeted therapies in a palliative setting. Multicentre cooperative group clinical trials are required to assess novel therapies to maximize patient resources in this uncommon tumor.

Expert consensus-based recommendations regarding key issues in the use of primary (or neoadjuvant) systemic treatment (PST) in patients with early breast cancer are a valuable resource for practising oncologists. PST remains a valuable therapeutic approach for the assessment of biological antitumor activity and clinical efficacy of new treatments in clinical trials. Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need fewer patients and are less expensive than adjuvant trial, and the endpoint of pCR is achieved in months, rather than years. For these reasons, the neoadjuvant setting is ideal for testing emerging targeted therapies in early breast cancer. Although pCR is an early clinical endpoint, its role as a surrogate for long-term outcomes is the key issue. New and better predictors of treatment efficacy are needed to improve treatment and outcomes. After PST, accurate management of post-treatment residual disease is mandatory. The surgery of the sentinel lymph-node could be an acceptable option to spare the axillary dissection in case of clinical negativity (N0) of the axilla at the diagnosis and/or after PST. No data exists yet to support the modulation of the extent of locoregional radiation therapy on the basis of the response attained after PST although trials are underway.

Purpose To assess the role of pathologic complete response (pCR) after neoadjuvant therapy as surrogate end point of disease-free survival (DFS) and overall survival (OS) in patients with breast cancer, we performed a trial-based meta-regression of randomized studies comparing different neoadjuvant systemic treatments. Methods The systematic literature search included electronic databases and proceedings of oncologic meetings. Endocrine therapy trials were excluded. Treatment effects on DFS and OS were expressed as hazard ratios (HRs), and treatment effects on pCR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome. Results Twenty-nine trials, 59 arms, and 30 comparisons, for a total of 14,641 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for DFS or the log(HR) for OS on the log(OR) for pCR demonstrated only weak associations (R2 = 0.08; 95% CI, 0 to 0.47; and R2 = 0.09; 95% CI, 0.01 to 0.41, respectively). Better associations were found in an exploratory analysis assessing a subset of trials comparing intensified/dose-dense chemotherapy versus standard-dose regimens (DFS: R2 = 0.79; 95% CI, 0.26 to 0.95; P = .003; and OS: R2 = 0.57; 95% CI, 0.19 to 0.93; P = .03). Conclusion This meta-regression analysis of 29 heterogeneous neoadjuvant trials does not support the use of pCR as a surrogate end point for DFS and OS in patients with breast cancer. However, pCR may potentially meet the criteria of surrogacy with specific systemic therapies.

Intravascular lymphomatosis (IVL) is a rare, malignant B- or T-cell lymphoma with remarkable affinity for the endothelial cells of small vessels, particularly within the skin and central nervous system. It is a disease that mimics several neurological disorders, particularly those of cerebrovascular ischemic origin. The prognosis is generally poor, with a rapidly fatal outcome. As a result the diagnosis is often made at post-mortem. We report a rare case of a 73-year-old patient with IVL complicated by intracerebral haemorrhage. In literature two cases of systemic IVL complicated by intracerebral haemorrhage have been reported, but they presented initially with a disseminated intravascular coagulation (DIC). This is the first case of brain IVL complicated by intracerebral haemorrhage not associated to DIC. Increasing awareness of this disease as a differential diagnosis to a common clinical presentation may lead to more opportunities to evaluate new diagnostic and treatment approaches.

Leptomeningeal dissemination of low-grade gliomas is an uncommon event. A 43-year old male presented with dizziness, gait ataxia, and diplopia. A nonenhancing lesion in the right cerebellar peduncle was identified, subtotally resected, and diagnosed as a grade II astrocytoma. After one year a nodular spread in the brain and leptomeninges was diagnosed, so the patient started chemotherapy with temozolomide and liposomal cytarabine. Complete remission was achieved after 12 months of treatment and the patient is still free from the disease after a follow-up of 24 months. We suggest that this combination may be a valuable treatment option.

We describe the case of a 39-year-old man with disseminated testicular seminoma that was refractory to salvage chemotherapy, and who had complete remission after imatinib administration. In September, 1999, the patient underwent a right orchifunicolectomy for a classical seminomatous tumour. A CT scan of the chest and abdomen showed retroperitoneal bulky disease (massive enlargement of right periaortic, paracaval, and interaortocaval lymph nodes of at least 4·3 cm in diameter). Baseline alpha-fetoprotein and human chorionic gonadotropin were within the normal ranges of 0·5–9·0 ng/ml and 0–2 mUI/ml, respectively, whereas lactate dehydrogenase concentration was increased at 722 UI/L (normal range 200–479 UI/L). The tumour was staged as pT1 N2. A classic chemotherapy regimen of cisplatin, etoposide, and bleomicin was given for three cycles, after which the patient’s concentrations of lactate de hydrogenase normalised and he had a complete response. The patient had standard follow-up according to the European Society for Medical Oncology recommendations. His fi rst relapse occurred in October, 2000, when retroperitoneal lymph-node involvement (right paracaval lymph nodes at least 5 cm in diameter that involved the right ureter and needed a pielostomy) and an increase in lactate dehydrogenase concentration to 1342 UI/L was noted. The patient underwent a classic second-line chemotherapy regimen with cisplatin, ifosfamide, and etoposide. A CT scan showed a reduction of the mean diameter of lymph nodes to 1 cm after two cycles, a complete response in all disease sites after four cycles, and normalisation of lactate de hydrogenase concentration to 293 UI/L after four cycles. At the end of chemotherapy, the patient received consolidation radiotherapy (2400 cGy in 12 fractions). A second relapse occurred 3 months later, with a CT scan showing lung metastases and supradiaphragmatic and infra diaphragmatic enlarged lymph-nodes. Tumour markers, including lactate dehydrogenase (326 UI/L), were normal. Between June, 2001, and November, 2001, after mobilisation and collection of peripheral-blood stem cells, the patient received two cycles of induction chemotherapy with gemcitabine and paclitaxel, followed by intensifi cation with high-dose chemotherapy (CARBOPEC—carboplatin, etoposide, and cyclophosphamide—with reinfusion of peripheral stem cells), and had a complete response in the thorax and a partial response in the abdomen with a residual mass of 1·5 cm disappearing 3 months later. In March, 2004, after 28 months of sustained complete remission, further restaging showed multiple bilateral metastases in the lung parenchyma (fi gures 1A and 1B). The CT scan did not show any infradiaphragmatic or supradiaphragmatic nodal metastases, unlike at the time of high-dose chemotherapy. Tumour markers were negative. A biopsy of the lung metastases was not done because CT images were indicative for secondary tumours. Because several investigators have reported KIT expression in a wide variety of human malignancies, and have shown that the kinase activity of KIT might be involved in the pathophysiology of some of these tumours—including germ-cell tumours and, more frequently, seminomas—we assessed KIT expression in the orchiectomy specimen by immunohistochemistry. Staining for KIT was strongly positive (fi gure 2). A standard avidin-biotin staining protocol was used with a polyclonal rabbit antibody for KIT (Dako A4502; Dako Corp, Carpinteria, CA, USA). The patient started receiving imatinib at the dose recommended for the treatment of gastrointestinal stromal tumours (400 mg/day). Treatment was well-tolerated, with Lancet Oncol 2007; 8: 1039–40

e12533 Background: Primary brainstem tumors (PBST) are the most common neoplasm of central nervous system (CNS) in children. In adults PBST is a rare disease, the incidence was reported to be 5% of...

e12537 Background: The prognosis of patients (pts) with recurrent HGG is poor with a median survival of 3 to 6 months. To date, no second line of treatment is recognized as standard. Enhanced angio...

Despite advances in surgical techniques, improvement in radiation treatments and chemotherapy, and the addition of new biological agents to the armamentarium, the median survival of patients with high-grade malignant glioma has changed little over recent decades. However, advances in the fundamental understanding of brain tumor biology suggest that targeting molecular pathways underlying carcinogenesis may provide alternative or additional approaches to glioma treatment. Viruses, particularly adenoviruses, have been critical in the application and development of these molecular approaches. Adenoviruses have been engineered to function as vectors for delivering therapeutic genes for gene therapy, and as direct cytotoxic agents for oncolytic viral therapy. The purpose of this review is to provide a prospective on the use of adenoviruses in high-grade malignant glioma therapy.

12534 Background: Temozolomide, a novel alkylating agent, has shown activity in the treatment of patients with high-grade gliomas. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant chemo- radiotherapy according to Stupp regimen. Methods: We reviewed our experience with a combination of radiotherapy (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). Results: 43 patients , median ECOG PS= 0, were treated with concomitant RT and Temozolomide at our institution since March 2004. Median age was 63 (range 33–73), with 62% over 60 years. All patients had histologically confirmed high grade gliomas: glioblastoma multiforme (32), grade III oligodendroglioma (3), grade III oligoastrocytoma (2), grade III astrocytoma (6). 2/43 patients underwent only a biopsy, the remaining underwent debulking surgery. At a median follow-up of 17 months, the median progression-free survival (PFS) was 6 mo and median overall survival (OS) was 12 mo. Median PFS and median OS were similar in elderly ( = 60 years). Treatment was well tolerated. Only one patient had grade IV haematological toxicity. One patient discontinued treatment due to hepatotoxicity. Conclusions: Our findings confirm the results of the EORTC trial(Stupp R et al., 2005) No significant financial relationships to disclose.

9575 Background: The use of adjuvant therapy should be based on appropriate prognostic factors. The aim of this study was to correlate the clinical, biological and pathological characteristics of women with breast cancer lesions of ≤1 cm. Methods: The 3033 patients with invasive operable breast cancer attending the Universitary and Civic Hospitals of Verona between January 1992 and June 2001 were divided into two groups: 664 women (21.9%) with lesions of ≤1cm (group A) and 2369 (78.1%) with lesions >1cm (group B). The patients with a diagnosis of ductal carcinoma in situ, lobular carcinoma in situ or breast sarcoma were excluded. The Chi-squared test and linear correlation were used to study the associations between lesion diameter and other variables. Results: Chi-squared test. Group A had fewer involved nodes (85.1% had no node involvement vs 55%, p