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Background: Several randomized clinical trials clearly demonstrated that adding palbociclib (P) to endocrine therapies (ET), such as letrozole (LT) or fulvestrant (FLV), significantly improves outcome both in first-line/endocrine sensitive and second-line/endocrine resistant hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2) metastatic breast cancer (MBC) patients (pts). The aims of the present study were to assess efficacy, activity and toxicity of P combined with either LT or FLV in a real world setting, and to study the efficacy and activity of treatments administered after progression to P + ET. Methods: Records of 245 consecutive HR+/HER2- MBC patients from 14 Italian cancer centers were reviewed in this observational study. Primary end-point was progression-free survival (PFS) obtained with P+ET; secondary end-points were overall response rates (ORR) and clinical benefit rate (CBR) obtained with P+ET and with post-progression treatments, as well as overall survival (OS), PFS to subsequent treatment lines and post-progression survival (PPS). Results: Overall 245 pts were treated with P+ET from April 2014. Of them, 116 (47%) received it in first-line setting, 70 (28%) in second-line and the rest (68 pts, 25%) in subsequent lines. Median age was 60 (35-80) years and median ECOG performance status was 0. Seventy-three pts (30%) had more than two metastatic sites and 75 (31%) had visceral metastasis. Ninenty-one (37%) pts received P+LT and 92 (37%) were treated with P+FLV. For 15 (6%) premenopausal pts an LHRH analogue was added to P+ET. In 77 (41%) patients a biopsy of a metastatic lesion was performed. Among the 116 pts treated in first-line setting, median PFS was 14.7 (95% CI 12.0-17.3) and 15.1 (95%CI 8.6-21.6) months for pts receiving P+LT and P+FLV, respectively. ORR was 48% (95% CI: 39-57%) and CBR was 75% (95% CI, 66-82%). Four (3%) complete responses (CR), 52 (45%) partial responses (PR), 31 (27%) stable disease (SD) and 11 (9%) progression disease (PD) were observed as best response; 18 pts were not yet evaluable. Among the 70 pts treated in second-line setting, median PFS was 10.8 (95%CI 0-24.3) and 7.9 (95%CI 3.3-12.5) months, for pts receiving P+LT and P+FLV, respectively. The ORR was 26% (95% CI: 16-38) and the CBR was 66% (95% CI, 53-76). One CR (1%), 17 PR (24%), 28 SD (40%) and 13 PD (18.5%) were observed as best response, while 9 were not yet evaluable. Best response was achieved after a median of 5 cycle. At time of the current analysis, 50 pts experienced PD during P+ET. Of them, 38 (76%) received chemotherapy (capecitabine, eribulin, nab-paclitaxel, paclitaxel+bevacizumab, vinoreline) and 12 (24%) ET. To date, only 5 pts progressed during these therapies, preventing us for evaluating secondary end-points regarding efficacy and activity. The most frequent adverse event (AE) was grade 3-4 neutropenia (31%), with febrile neutropenia reported in 5 (2%) cases. Main non-hematological AEs were fatigue and gastrointestinal symptoms (diarrhea and stypsis). Conclusions: Our findings confirm the efficacy and safety of P+ET as first/second-line treatment for HR+/HER2- MBC pts, even in a non-selected, real world population. Since data regarding the efficacy and activity of post-progression therapies were not mature at the time of the current analysis, they will be subsequently presented. Citation Format: Alessandra Fabi, Michelangelo Russillo, Mariangela Ciccarese, Simone Scagnoli, Francesco Schettini, Giuseppe Buono, Vito Lo Russo, Grazia Arpino, Rosalba Rossella, Giuseppina Sarobba, Marianna Giampaglia, Patrizia Pellegrini, Simonetta Stani, Michela Palleschi, Vincenzo Adamo, Francesca Morelli, Maria Agnese Fabbri, Cecilia Nistico, Gianluigi Ferretti, Giovanna Catania, Simona Pisegna, Diana Giannarelli, Francesco Cognetti. Real-world evidence of efficacy and activity of palbociclib plus endocrine therapy and post-progression treatments in HR+/HER2- metastatic breast cancer patients: The PALPract study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-18.

Background: To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC). Objectives: The present study assesses, in a real-world setting, the activity of different subsequent therapies in patients who experienced a PD on palbociclib (P) + endocrine therapy (ET), to evaluate the best therapy sequence. Methods: This is a multicenter retrospective observational study. Records of consecutive HR+/HER2- MBC patients from January 2017 to May 2019 were reviewed. The primary endpoint was the evaluation of progression-free survival (PFS) according to subsequent treatment lines after progression on P+ET. Toxicity data were also collected. Results: The outcomes were analyzed in 89 MBC patients that had progressed on previous P+ET: 17 patients were on hormone therapy (HT) and 31 patients on chemotherapy (CT) as second-line treatments; seven patients were on HT and 34 on CT as third-line therapies. PFS of patients treated with HT as second-line therapy is significantly improved when compared with patients treated with CT (p=0.01). Considering third-line settings, the difference in PFS was not statistically different between HT and CT. A better outcome in terms of toxicity is observed among HT patients for both second- and third-line therapies. Conclusions: patients who were progressive on P+ET could still benefit from a subsequent ET. In patients who experienced a good efficacy from prior ET, without visceral metastatic sites, HT seems the most suitable option, when compared to CT, also in terms of safety.

Background We reported the results of an Italian large retrospective analysis that evaluated the effectiveness and safety of T-DM1 in ‘field-practice’ breast cancer patients. We performed a sub-analysis to investigate the clinical activity of T-DM1 in patients with brain metastases (BMs). Methods The records of 87 adult women with HER2-positive breast cancer and BMs treated with T-DM1 were reviewed. Their clinical outcomes were compared with those of 216 patients without central nervous system (CNS) involvement. Results Response to T-DM1 treatment in BMs was available for 53 patients in the BM group (60.9%): two patients reported a complete response (3.8%), 11 patients obtained partial response (20.7%; overall response rate: 24.5%), 16 patients had a stable disease (30.1%). Regarding extracranial disease, a total of 77 and 191 patients were evaluable for response in BM group and non-BM group, respectively. The overall response rate was 35.1% in the BM group and 38.3% in the non-BM group; disease control rate was 53.3% and 66.6%, respectively. At a median follow-up of 16 months (range: 1–55), median cumulative progression-free survival (PFS) was 7 months (95% CI: 5.4–8.6) in the BM group and 8 months (95% CI: 5.7–10.3) in the non-BM group. In the second-line setting, PFS was 5 (95% CI: 3.1–6.9) versus 11 (95% CI: 7.1–14.9) months (p = 0.01). Overall survival was 14 months (95% CI: 12.2–15.8) in the BM group and 32 months (95% CI: 24.4–39.6) in the non-BM group (p Conclusions T-DM1 is active in breast cancer patients with BMs.

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this ‘field-practice’ study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively. In conclusion, in this ‘real-word’ study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatinib.

Background: T-DM1 showed remarkable activity in metastatic HER-2 positive breast cancer (mBC) and it was recently approved for clinical use in patients (pts) who previously failed Trastuzumab- and Taxanes-based therapies. Currently, little is known on the performance of T-DM1 in a “real life” scenario. Therefore, we investigated effectiveness and safety of T-DM1 in Italian daily practice. Methods: Pts baseline characteristics and clinical outcome of pts with HER-2 positive mBC treated with T-DM1 between 2013 and 2015 at 20 Italian Institutions were retrospectively collected and analyzed. Results: 300 pts were included in our analysis. Median age was 51 years (27-78); visceral metastases were present in 204 (68%) pts and brain metastases in 86 (29%). It is noteworthy that 111 (37%) pts received T-DM1 as pure second line, 83 (28%) as third line and 96 (32%) as further lines. Moreover 10 (3%) pts had T-DM1 as first line because disease recurrence occurred during or adjuvant trastuzumab of within 6 months of its completion. The overall response rate (ORR) was 40%, global disease control rate (gDCR) 64%, median progression-free survival (PFS) 7.0 months (C.I.95%: 5.6-8.4) and overall survival (OS) at 2 years 63%. Pts with 1, 2 and 3 or more metastatic site had OS at 2 years of 87%, 67% and 46%, respectively (p Conclusions: To our knowledge, this is the first real life, multicenter retrospective analysis evaluating efficacy and safety of T-DM1 in pretreated HER-2 positive mBC pts. We observed remarkable results in terms of PFS and OS, especially when T-DM1 was given early in the course of metastatic disease. Shortened PFS in patients progressing after pertuzumab suggest further analyses to better define possible molecular mechanisms of cross-resistences between two molecules. As a whole there was no evidence of significant or unexpected toxicities. Although these findings should be taken with caution due to the retrospective analysis and the different lines of previous treatment considered, we confirmed the potential therapeutic role of T-DM1 across a heterogeneous population of HER-2 positive mBC patients. The final analysis will be presented to the meeting. Citation Format: Fabi A, De Laurentiis M, Caruso M, Valle E, Moscetti L, Santini D, Cannita K, Carbognin L, Ciccarese M, Rossello R, Arpino G, Leonardi V, Montemurro F, La Verde N, Generali DG, Zambelli A, Scandurra G, Russillo M, Paris I, D'Ottavio AM, Filippelli G, Giampaglia M, Stani S, Fabbri A, Alesini D, Giannarelli D, Cognetti F. T-DM1 in HER2 positive advanced breast cancer patients: Real world practice from a multicenter observational study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-11.

BACKGROUND: Everolimus, an mTOR inhibitor, in combination with exemestane is approved for hormone receptor (HR) positive advanced breast cancer (ABC), after failure of treatment with non-steroidal aromatase inhibitor (NSAI). We assessed the toxicity of the combination and the correlation between dose intensity and response to therapy, in a real world population of ABC from 11 Italian centers. Moreover, we evaluated OS of the whole population, RR and PFS according to line of treatment (from 1rd to 3th and from 4th on). METHODS: 154 pts were treated with combination of everolimus 10 mg and exemestane 25 mg daily from 05/2011 today. Median age was 62 (47-82). Median time to metastatic disease was 49 months (0-269). Median number of metastatic sites was 2 (55.2% of pts visceral versus 44.8% non visceral disease). N=117 (75.9%) pretreated with HT as adjuvant; N=126 pts (81.8%) treated with HT for advanced disease prior to EVE/EXE, with a median of one line (0-5). N=102 pts (66.2%) treated with chemotherapy for metastatic disease, with a median of one line (0-6) before everolimus treatment. RESULTS: Sixteen pts received EVE/EXE as 1st line (10.4%), 39 as 2nd (25.3%), 37 as 3rd (24%), 62 as 4th or more (40,3%). Response was evaluable in 127 out of 154 pts; CR/PR/SD respectively 5/27/56 pts. RR according to line (from 1st to 3rd vs ≥ 4th) was respectively 22.8% vs 26.4% (p=0,864). The median PFS for all population (150 pts) was 38 weeks (95% CI: 33-42). The PFS according to line (1st- 3rd vs ≥ 4th) was 38 wks in both subgroups, p=0.73. OS (126/154 pts) was 28 mths (95% CI: 31-38). The most frequent adverse events were collected in the table. Adverse eventsOverall %Grade 3-4 %Stomatitis55.810.4Hypercholesterolemia47.40.0Asthenia42.95.2Hyperglycemia36.45.8Hypertriglyceridemia29.20.6Anemia28.63.9Peripheral edema24.71.3Rash23.40.6Increased ALT/AST/GGT21.46.5Thrombocytopenia19.53.9Diarrhea18.81.9Weight loss18.21.3Dysgeusia17.50.6Pneumonitis15.61.9Cutaneous toxicity14.90.6Infection14.33.2Neutropenia11.71.9Nausea11.70.0Anorexia (without stomatitis)10.41.3Electrolyte alterations9.71.3Urea/creatinine increase6.51.3Vomiting6.50.0Uric acid increase4.50.0 Median duration of treatment with everolimus 10 mg and 5 mg was respectively 180 (9-854) and 129 days (3-738). Fifty-eight pts (37,6%) never stopped treatment with everolimus 10 mg; 16 pts (10,4%) definitively stopped everolimus for toxicity; 80 pts (52,0%) temporarily interrupted the treatment, resuming at dose level 10 mg (31 pts) or reducing at 5 mg (49 pts). Main reason for discontinuation/interruption was stomatitis G2-G3. RR and PFS evaluated according to dose intensity, 10 mg vs 5 mg, were respectively 25.9% vs 30% p=0.779, 38 wks (27-44) vs 40 wks (31-48) P=0.614 CONCLUSIONS: efficacy in terms of RR and PFS of the combination EVE/EXE is not related to dose intensity (10 mg vs 5 mg), the discontinuation of the treatment is high with the starting dose of 10 mg, the toxicity is consistent with previous phase II-III studies although we collected some different toxicities. Citation Format: Forcignanò R, Petrucelli L, Cazzaniga ME, Lupo LI, Chiuri VE, Cairo G, De Matteis E, Febbraro A, Giordano G, Campidoglio S, Fabi A, Giampaglia M, Bilancia D, La Verde N, Maiello E, Morritti M, Giotta F, Lorusso V, Scavelli C, Romito S, Cusmai A, Palmiotti G, Tornesello A, Ciccarese M. Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real world population of hormone receptor positive advanced breast cancer: A multicenter Italian experience. [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 P4-13-15.

Aim: This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability. Methods: 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C). Results: RR was 29.8% (A), 27.8% (B) (p = 0.953), and not evaluable (C). PFS was 9 months (95% CI 7–11) (A), 10 months (95% CI 9–11) (B), and 5 months (95% CI 2–8) (C), p = 0.956. OS was 38 months (95% CI 24–38) (A), median not reached (B), and 13 months (95% CI 10–25) (C), p = 0.002. Adverse events were stomatitis 57.7% (11.0% grade 3–4), asthenia 46.0% (6.1% grade 3–4), hypercholesterolemia 46.0% (0.6% grade 3–4), and hyperglycemia 35.6% (5.5% grade 3–4). The main reason for discontinuation/interruption was grade 2–3 stomatitis. Conclusions: No correlation was found between dose intensity (5 vs. 10 mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy.

Aim: We evaluated the outcomes of patients treated with ado-trastuzumab emantasine (T-DM1) after first-line pertuzumab/trastuzumab, compared with those receiving a trastuzumab-only-based regimen. Patients & methods: Patients who received second-line T-DM1 after pertuzumab/trastuzumab (n = 34) were compared with those who received only trastuzumab (n = 73). Results: Overall response rate was 33.3% in patients with prior pertuzumab and 57.1% in the remaining subjects. Disease control rate was 47 and 43%, respectively, and the clinical benefit rate was 43.3 and 71.1%, respectively. Median progression-free survival was 5.0 and 11.0 months, respectively (hazard ratio: 2.02; 95% CI: 1.14–3.58; p = 0.01). Conclusion: Patients treated with T-DM1 who previously received pertuzumab present poorer clinical outcomes compared with those receiving a trastuzumab-only-based regimen in the first-line setting.

Locally advanced cervical cancer has a poor prognosis and is difficult to treat by surgery; authors’ evaluated feasibility and safety of the simultaneous integrated boost (SIB) technique for dose escalation in patients with cervical cancer using a rotational dynamic Intensity Modulated Radiation Therapy Technique (VMAT®). Authors evaluated 10 patients affected by loco-regionally advanced, node negative, inoperable cervical cancer. All women received primary chemoradiation (CRT). Six pts received three cycles of platinum-based chemotherapy (CT) plus CRT. Three Programmed Temperature Vaporization (PTV) were delineated: PTV1 (primary, cervix and parametria with a 1cm-margin); PTV2 (body of uterus with a 1cm-margin); PTV3 (pelvic nodes). PTV1 was defined using image fusion between CT-scan and RM or PET/CT. Treatment plans, calculated using a rotational dynamic Intensity Modulated Radiation Therapy (IMRT) system on Oncentra Masterplan® (VMAT®), and consisted in a simultaneous integrated boost. Total treatment time was 45 days. Concomitant CT consisted of weekly cisplatin 40 mg/m2. Dose–volume histograms and acute gastrointestinal, genitourinary, and hematological toxicity were evaluated. Secondary endpoint was evaluation of short term disease free survival. Three months after CTRT, patients were revaluated with colposcopy and cytology and Pelvic imaging. After six and twelve months from CTRT, reevaluation included PET-CT or Chest CT scan and Abdominal and Pelvic RM. All patients concluded radiation without suspension. Cytology demonstrated complete response (CR) in 4 pts in the ERT fraction of brachytherapy (BRT) group and in 1 pts in ERT alone group. All other patients showed a partial response (PR) > 75%. After a median follow up of 20 month (range 16-22), 5 patients are free from disease (NED), 4 patients are alive with disease (AWD) and 1 patient died after three months (DOD). In 2 AWD patients, re-staging PET showed a RC of pelvic disease with evidence of disease in lomboaortic nodes. One of them received salvage radiation therapy on recurrence. After this preliminary experience, in patients with inaccessible cervical canal, authors could propose the dose escalation on PTV1, with the aim of delivering BED as near as possible to 85Gy.

Introduction The goal of pharmacological prophylaxis of chemotherapy-induced nausea and vomiting (CINV) should be the elimination of both nausea and vomiting symptoms during all planned chemotherapy cycles. The aim of this study was to assess the efficacy of a single dose of palonosetron and dexamethasone to prevent CINV and to guarantee an adequate food intake (FI) in patients receiving several cycles of multiple day-based chemotherapy (MD-CT). Methods Patients with advanced cancer but without a compromised nutritional status (bone mass index ≥ 18.5) were treated with 0.25 mg palonosetron plus 20 mg dexamethasone before MD-CT. The MD-CT regimen was either epirubicin plus ifosfamide or paclitaxel plus cisplatin and ifosfamide. Nausea, vomiting, and FI were monitored in a 7-day diary. Complete response (CR: no vomiting and no rescue therapy) was the primary endpoint, while complete control (CC: CR and no more than mild nausea) and the evaluation of FI were secondary endpoints. The endpoints were evaluated during the overall timescale (0–168 h) of the chemotherapy regimen. Results Fifty patients were enrolled, 80% of whom achieved CR and 78% achieved CC. During the six chemotherapy cycles, CR and CC ranged from 76% to 88% and from 62% to 88%, respectively. Moreover, patients with CR had a significantly (p

Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.

The aim of our study was to evaluate the efficacy of a single-dose palonosetron plus dexamethasone to control emesis in patients (pts) receiving HEC. Moreover, we evaluated the amount of their food intake (FI) in the week following therapy, in order to measure any reduction of calories consumption related to Chemotherapy-induced nausea and vomiting (CINV). Patients affected with advanced cancer were treated with palonosetron 250 mcg plus dexamethasone 20 mg before HEC. Nausea, vomiting, and FI were monitored by a 7-day diary. Complete Response (CR: no vomiting and no rescue therapy) was the primary endpoint, Complete Control (CC: CR and no more than mild nausea) and the evaluation of FI were the secondary endpoints. The endpoints were evaluated during the acute (0–24 h), the delayed (25–168 h) and overall (0–168 h) phases. Thirty-five patients were enrolled; 85.7% and 82.9% of patients achieved CR and CC respectively, during the acute phase; 82.9% and 77.1% of patients achieved CR and CC, during the delayed phase; 80% and 77.1% of patients achieved CR and CC, during the overall phase. During the acute phase, patients with a CC without nausea had a median daily FI of 1,575 kcal, whereas patients with CC and presence of mild nausea had a median daily FI of 1,040 kcal (−535 kcal; p

Introduction: Treatment of elderly patients with small cell lung cancer (SCLC) is based on scanty evidence. Methods: Patients with extensive SCLC, age >70 years, and performance status 0-2 were eligible for a study looking for optimal two-drug combination of gemcitabine (Gem) with vinorelbine (Vin), etoposide (Eto), cisplatin (Cis), or carboplatin (Car). Gemcitabine dose was the same (1000 mg/m2, days 1-8) in all combinations. A two-stage minimax flexible design for response was applied to GemVin combination (Vin 25 mg/m2, days 1-8). For GemCar, GemCis, GemEto, a phase I-II Bayesian design was applied, looking for the optimal dose of the partner drugs. Objective response rate ≥60% and unacceptable toxicity ≤25% were required to define a combination worthy of further studies. Results: Median age of 78 eligible patients was 74 years. GemVin produced a 36.7% objective response rate. GemEto and GemCis arms were found not sufficiently active. GemCar produced 16 responses (14 with area under the curve [AUC] 3.5 and 2 with AUC 4.0) in 26 patients (61.5%) and 6 cases of unacceptable toxicity (3 at each Car dose). Conclusions: In elderly patients with extensive SCLC, GemVin, GemEto, and GemCis are not enough active and do not merit further studies. Gem plus Car might deserve further attention. © 2011 by the International Association for the Study of Lung Cancer.

In the last years, ovarian cancer research has centred particularly on disease prevention, but an increasing number of women are occurring to gynaecology and clinical genetics clinics with family history of ovarian cancer and inherited familial mutations. Over the past 15 years, there has been substantial improvement in the understanding of hereditary ovarian cancer.

Gastrointestinal cancer (GI) incidence increases with each decade of life and is the leading cause of death in patients aged70 years. Nevertheless, elderly patients are often excluded or underrepresented in clinical trials. We performed a review of current recommendations in the management of GI elderly cancer patients.A comprehensive literature review was performed analyzing data about several meta-analysis and studies regarding chemotherapeutic regimens in elderly patients with colorectal and gastroesophageal cancers.Most of the studies demonstrated that the elderly experience the same advantages and toxicities from chemotherapy as younger individuals despite the fact that the data reviewed in this article provide evidence that elderly with GI cancers are underrepresented in clinical trials and few trials are conducted addressing the different risks and aims in older population. Each individual should be assessed for an appropriate regimen of treatment in the adjuvant or metastatic gastrointestinal cancer setting, and the decision of how to treat elderly must incorporate goals and preferences of the patient after a careful discussion of risks and benefits.Chronological age alone is not a sufficient factor to withhold curative/palliative treatment from an elderly GI cancer patient, and cofactors regarding their functional, social, and mental status have to be considered. For this purpose, several tools exist that may be utilized, such as geriatric assessment scores, comorbidity indices, frailty indices, scores for predicting toxicity from chemotherapy, and prognostic indices for survival.

Breast carcinoma is a complex and heterogeneous disease and several different molecular alterations are involved in its pathogenesis and progression. Different growth factor receptor-driven signaling pathways sustain the growth and survival of breast cancer cells. Actually, three targeted agents are available for the treatment of breast cancer: trastuzumab, a monoclonal antibody directed against the human epidermal growth factor receptor-2 (HER2); lapatinib, an oral available dual tyrosine-kinase inhibitor of the human epidermal growth factor receptor-1 (HER1, EGFR) and HER2; bevacizumab, a monoclonal antibody directed against the vascular endothelial growth factor (VEGF). All these agents demonstrated to be synergistic with chemotherapy. In addition, recently concluded clinical trials suggest that signaling inhibitors can prevent or overcome resistance to endocrine therapy in estrogen receptor positive (ER+) breast cancer. Moreover, several other targeted drugs are under investigation in clinical trials. The aim of this review is to give a synthetic but complete picture of various targeted agents for breast cancer therapy that are under clinical trials or currently available in clinical practice.

Vinorelbine (i.v.) plus capecitabine (oral) combination therapy is active in anthracycline/taxane pretreated patients with metastatic breast cancer. Availability of oral vinorelbine provides this combination in an all-oral formulation. Two consecutive phase II trials differing only in vinorelbine administration routes evaluated their respective activities and tolerabilities in this population. In the i.v. group (n = 38) disease control was 61% (37% PR, 24% SD), median TTP 6.8 months and median survival 11.3 months. In the oral group (n = 38) disease control was 77% (5.4% CR, 34% PR, 38% SD), median TTP 7 months and median survival 10 months. G3-G4 neutropenia was more common in the oral group (p < 0.05); G2-G3 anaemia [5] and G3 thrombocytopenia [1] were observed only in the oral group. Although the comparison between the two regimens was not randomized, the results observed in these two consecutive phase II studies may suggest that oral and iv vinorelbine, in combination with capecitabine, can achieve similar responses in patients with metastatic breast cancer refractory to anthra-taxane combinations.

Background: Vinorelbine i.v. and capecitabine are two of the most effective single agents in previously treated advanced breast cancer (ABC). A number of studies have been reported with the combination of these agents. Actually, the availability of oral formulation for vinorelbine allows a full oral combination of the two agents. The aim of this study was to evaluate the activity and toxicity of this novel combination. Patients and methods: Thirty-eight advanced breast cancer patients refractory to anthracyclines and taxanes were included in this study. Treatment consisted of vinorelbine 60 mg/m 2 (days 1 + 8), and capecitabine 2000 mg/m 2 (days 2–7 and 9–16) every 3 weeks. Results: A total of 228 courses were given with a mean of three cycles/patient (range 1–12). Five patients (13.1%) had no toxicity at all. Hematologic side-effects were: neutropenia grade 2–3 in seven patients (18.9%) and grade 4 in one patient (2.7%), anemia grade 1 in 11 patients (29.7%), grade 2–3 in five patients (13.5%), thrombocytopenia grade 1 in six patients (16.2%) and grade 3 in one patient (2.7%). Non-hematologic side-effects were: fatigue grade 1 in five patients (13.5%), hand–foot syndrome grade 1 in two patients (5.4%) and grade 2 in two patients (5.4%), nausea/vomiting grade 1 in two patients (5.4%), grade 2 in three patients (8.1%) and grade 3 in one patient (2.7%), constipation grade 1 in two patients (5.4%), peripheral neurotoxicity grade 1 in three patients (8.1%) and grade 2 in one patient (2.7%), gastric pain grade 1 in two patients (5.4%), stomatitis grade 1 in three patients (8.1%) and grade 2 in one patient (2.7%). Out of 38 patients assessable, we observed two (5.4%) CR, 13 (34 %) PR, 14 (37.8%) SD and nine (26.3%) PD. The median time to progression was 4.5 months (range 1–18 months), the median response duration was 7 months (range 2–18 months) and the median survival duration was 10 months (range 2–26+). Conclusions: The oral vincap should be considered as an alternative to single agent capecitabine or vinorelbine in ABC refractory to antra-taxane combination.

e20681 Background: Erlotinib is a potential treatment option for elderly patients with advanced NSCLC; it has demonstrated a survival advantage vs BSC in the BR.21 study after 1st/2nd line failure and a good safety profile in elderly pts. Methods: Wereviewed the medical records of pts over 70 yearstreated with Erlotinib in the last 5 years in our Unit in order to correlate response to pts characteristics. EGFR mutation status (Ems) was not determined in any pts. Response was evaluated by CT scan every 2 months. Results: Since October 2006 we have treated 84 elderly pts with stage IIIb/IV NSCLC as 2nd/3rd/4th line of therapy. Median age was 75 (range 70-90), 62 (73.8%) were males and 22 (26.2%) women, respectively. Histology was ADK in 46 (54.8%), SQM in 31 (36.9%), other in 7 (8.3%). Stage IIIb/IV was 19/65 (22.6%/77.4%). PS was 0 in 7 (8.3%), 1 in 67 (79.8%), 2 in 9 (10.7%), 3 in 1 (1.2%) pts. With regard to smoking status,15 (17.8%) pts were never smoker, 59 (70.2%) ex smoker and 10 (12%) currently smoker. Patients treated as 2nd/3rd/4th line were 59/23/2 (70.2%/27.3%/2.4%). Overall, 3 pts achieved PR (3.6%), 33 SD (39.3%), 48 PD (57.1%). The characteristics of responding pts were: female, ADK, never/ex smokers, PS 0/1, 2nd line. Clinical benefit rate was 42.8%, 60.8% in ADK (28/46), 16.1% in SQM pts (5/31), 42.9% in other pts (3/7). The median duration of response (Mdr) was 20.3 months (range 11-36), Mdr of SD was 34 (range 7-55). Responding pts had a median survival of 43 months (range 34-59). Conclusions: In our series of elderly pts, Erlotinib was more effective in female, PS ≤ 2, ADK, and 2nd line. This drug can be considered a good alternative to chemotherapy in elderly pts with ADK and good PS, irrespective of mutational status of EGFR.

e20681 Background: Erlotinib is a potential treatment option for elderly patients with advanced NSCLC; it has demonstrated a survival advantage vs BSC in the BR.21 study after 1st/2nd line failure ...

e18048 Background: Erlotinib is an oral tyrosine kinase inhibitor, approved for treatment of advanced NSCLC after the failure of more than 1 or 2 previous chemotherapy regimens. Its efficacy is comparable to that of chemotherapy, however, some concerns have been raised on its activity in pts with poor PS or in those not harboring EGFR mutation. Methods: Wereviewed the medical records of pts treated with erlotinib in the last 5 years in two Oncologic Centers of South Italy, with the aim to correlate response to pts characteristics. Results: Since January 2006 we have treated with erlotinib 388 pts affected by stage IIIb-IV NSCLC as 2nd, 3rd or 4th line of therapy. Median age was 67 (range 23-90), 300 were males and 88 women. Histology was ADK in 214 (55.2 %), SQM in 129 (33.2%) BAL in 12 (3.1%) and other in 33 (8.5%). Stage IIIb/IV was 66/322 (17%/83%). PS was 0 in 90 (23.5%), 1 in 214 (57.4%), 2 in 60 (15.5%) and 3 in 14 (3.6%) pts, respectively. Smoking status was: never smoker 60 (15.6%), ex smoker 276 (71%), currently smoker 52 (13.4%). With regard to the line of therapy, 250 pts (64%) were treated as 2nd line, 113 (29.1%) as 3rd line and 25 (6.5%) as 4th line. Overall, 117 pts (30%) received only the first drug supply and were lost to follow-up, 131 (33.4%) received 2 or 3 drug supplies, 134 (35.7%%) 4-30 drug supplies and 5 pts (0.9%) > 30 drug supplies, respectively. According to RECIST Criteria, 20/256 evaluable pts (11 too early, 121 not evaluable) achieved PR (7.8%), 74 SD (28.9%) and 162 (63.2%) progressed. The characteristics of the responding pts were as follows: 12 women and 8 men, 15 ADK, 4 SQM and 1 other histology (undifferentiated), 9 never smoker, 10 ex smoker and 1 current smoker, PS 0/1/2 in 8/9/3 pts; line of therapy 2nd/3rd/4th in 16/4/0. The median duration of response was 10 months (range 3 to >30). Median duration of SD was 9 months. Responding pts had a median survival of 28 months (range 3-105). Conclusions: These retrospective data suggest a more cautious usage of the drug, in order to avoid the huge number of pts lost to follow-up. In fact, erlotinib should not be prescribed in pts with poor PS and in lines beyond the 3rd, unless for pts harboring EGFR mutation.

e11123 Background: HER-2 is a 185 kd protein composed of three domains: a cytoplasmatic domain, a transmembrane domain and an extracellular domain (ECD). The ECD of HER-2 can be cleaved from the su...

10673 Background: Vinorelbine i.v. and capecitabine are two of the most effective single agents in previously treated advanced breast cancer (ABC). A number of studies have been reported with the combination of these agents. Actually, the availability of oral formulation for vinorelbine allows a full oral combination of the two agents. The aim of this study was to evaluate the activity and toxicity of this novel combination. Patients and Methods: Thirty-eight advanced breast cancer patients (pts) refractory to anthracyclines and taxanes were included in this study. Treatment consisted of vinorelbine 60 mg/m2 (days 1 + 8), and capecitabine 2000 mg/m2 (days 2–7 and 9–16) every 3 weeks. The pt characteristics were: median age 53 years (range 37–77 years); ECOG PS 0–1 in 35 pts (92.1%), and PS 2 in 3 pts (7.8%); ER+/PgR+ 20 pts (52.6%) and ER−/PgR− 11 pts (28.9%). Dominant sites of disease were visceral in 19 pts (50.0%), bone in 10 pts (26.3%), soft tissue in 9 pts (23.6%). Results: A total of 228 courses were given with a mean of three cycles/pt (range 1–12). Five pts (13.1%) had no toxicity at all. Hematologic side-effects were: neutropenia G2-G3 in 7 pts (18.9%), and G4 in 1 pt (2.7%), anemia G1 in 11 pts (29.7%), G2-G3 in 5 pts (13.5%), thrombocytopenia G1 in 6 pts (16.2%) and G3 in 1 pt (2.7%). Non-hematologic side-effects were: fatigue G1 in 5 pts (13.5%), hand-foot syndrome G1 in 2 pt (5.4%) and G2 in 2 pts (5.4%), nausea/vomiting G1 in 2 pts (5.4%), G2 in 3 pts (8.1%) and G3 in 1 pt (2.7%), constipation G1 in 2 pts (5.4%), peripheral neurotoxicity G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%), gastric pain G1 in 2 pts (5.4%), stomatitis G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%). Out of 38 pts assessable, we observed 2 (5.4%) CR, 13 (34 %) PR, 14 (37.8%) SD, and 9 (26.3%) PD. The median time to progression was 4.5 months (range 1–18 months), the median response duration was 7 months (range 2–18 months), and the median survival duration was 10 months (range 2–26+). Conclusions: The oral vincap combination was well tolerated and effective in ABC. In fact, this regimen achieved results comparable to the previously reported combinations of capecitabine and i.v. vinorelbine. The oral vincap should be considered as an alternative to single agent capecitabine or vinorelbine in ABC refractory to antra-taxane combination. No significant financial relationships to disclose.

A number of second line treatments have been proposed in patients with advanced pretreated non-small cell lung cancer (NSCLC). However, either single agents or two or three drug combinations achieved very poor results with no superiority of any combination over monotherapy. We have treated 42 patients (30 males) affected by advanced/metastatic NSCLC progressing during front line cisplatin-based chemotherapy with a combination of topotecan (1.2 mg/m2) plus ifosfamide (1200 mg/m2) for 3 consecutive days every 3 weeks. The median age was 63 years (range 43-76); cell types were: squamous carcinoma (n=17), adenocarcinoma (n=16), large cell carcinoma (n=3), broncho-alveolar carcinoma (n=2) and undifferentiated carcinoma (n=4). All patients were treated with a platinum containing chemotherapy: 39 patients with cisplatin, 2 patients with carboplatin and 1 patient with oxaliplatin, respectively. The ECOG PS was 0 in 8 patients (19%), 1 in 11 patients (26%), and 2 in 23 patients (55%). The median number of courses administered was 3 (range 1-8). Grade 3-4 neutropenia was the dose limiting toxicity, observed in 36% of patients. Moreover, grade 3-4 anemia and thrombocytopenia were observed in 17% and in 12% of patients, respectively. One PS 2 patient died of grade 4 hematological toxicity after the first cycle. No complete response was observed. Six (14.2%) subjects obtained a partial response (PR). In addition, 1 (2.4%) minimal response (MR) plus 14 (34%) stable diseases (SD) and 21 (51%) progressive diseases (PD) were observed. Median time to disease progression and median survival were 9 weeks (range 1-13) and 26 weeks (range 1-91+), respectively. The 1-year survival rate was 14%. Combination of topotecan and ifosfamide demonstrated antitumor activity in patients with relapsing or refractory NCSLC with a modest side effect profile and an overall disease control (PR + MR + SD) of 50.7%. Nevertheless, the still low response rate and the shortness of median survival indicates the need for more effective second line treatments in this disease.