Background: State health insurance authorities in Greece do not reimburse genetic testing for cancer predisposition. The Hellenic Society of Medical Oncology has launched and carries out a national program covering genetic testing for BRCA1/2 mutations detection, with the financial support of pharmaceutical industry. Aim: This analysis evaluates how, during this program, access to genetic testing transformed the oncologists' therapeutic approach toward their ovarian cancer patients and how the results impacted treatment decisions concerning PARP inhibitors. Adoption of testing by healthy relatives and timing of testing in the disease continuum were also evaluated. Methods: Adult patients with high-grade epithelial ovarian carcinoma, irrespectively of family history or age at diagnosis were eligible for this program. Genetic counseling was recommended before testing, and both were offered at no financial cost. First degree family members of pathogenic mutation carriers were also offered free counseling and testing. Results: From March 2015 through January 2018, 708 patients were enrolled and tested. One hundred and forty seven (20.7%) mutation carriers were identified, 102 (14.4%) in BRCA1 and 45 (6.3%) in BRCA2 gene. Testing was more often pursued at initial diagnosis (61%) than at recurrence (39%), as recorded for 409 patients with available relevant information. During the 1st year of the program, average monthly tests performed were 25.1, while during the 3rd year this number increased to 34.3 tests per month. Among patients who tested positive for deleterious BRCA1/2 mutations, relapse was reported in 58 patients, 94.8% of which (n= 55) received treatment with the PARP inhibitor olaparib as per its indication. Family members of 21 patients (14.3%), out of the 147 who tested positive, received genetic counseling and testing for the mutation identified in the context of the program. Conclusion: Free access to genetic testing for BRCA1/2 for ovarian cancer patients and genetic consultation facilitates testing uptake, affects common clinical practice & has major impact on patients and their families. Still, diffusion of genetic information and broader testing of family members require further efforts by the oncological community.

Background: Bevacizumab is the first antiangiogenic agent approved for treatment of advanced non-squamous NSCLC. Elderly or other "fragile" patients, such as those with poor performance status (PS), comprise the majority of the NSCLC population, but are typically underrepresented in clinical trials. The primary aim of this study was to investigate the efficacy and safety of first-line bevacizumab in "real-world" patients with advanced NSCLC. Methods: The medical records of all patients with histologically or cytologically confirmed advanced-stage non-squamous NSCLC, treated with first-line bevacizumab (plus chemotherapy) at the Oncology Clinic of "Sotiria" Athens University Hospital between January 2008 and December 2012 were retrospectively reviewed. Selected patients were stratified according to age, i.e. elderly (> 70 years) vs non-elderly (≤70 years), ECOG PS (0-1 vs 2-3) and other demographic, clinicopathological and treatment data. Main outcome measures were overall survival (OS) and treatment-related toxicity. Results: A total of 145 cases (mean age/SD=61.7 ± 10.6 years) were included. 23,4% of patients were elderly, while 15.8% had poor PS (2-3). Maintenance bevacizumab (with or without pemetrexed) was administered in 24.1% of all cases, including only patients with good PS, and mainly non-elderly. The presence of comorbidities was significantly associated with poor PS and age> 70 years. No statistically significant difference with regard to OS, or type and frequency of side effects was observed between elderly and non-elderly patients. A similar toxicity profile was also observed between patients with good versus poor PS. Absence of maintenance bevacizumab and poor PS were both significantly associated with reduced OS, both in univariate [HR (95% CI): 0.45 (0.22-0.9); p = 0.023 and HR (95% CI): 2.16 (1.29-3.64); p = 0.004, respectively] and in multivariate analysis [[HR (95% CI): 0.47 (0.22-0.99); p = 0.048 and HR (95% CI): 1.76 (1.04-3.00); p = 0.036, respectively]. Conclusions: Our findings suggest that first-line bevacizumab may show similar efficacy and toxicity in elderly versus non-elderly patients with advanced NSCLC. Further prospective data are needed to confirm these observations. Legal entity responsible for the study: University of Athens Funding: University of Athens Disclosure: All authors have declared no conflicts of interest.

Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine.

The addition of bevacizumab to the first-line chemotherapy of advanced non-small cell lung cancer (NSCLC) of non-squamous histology has been shown to improve survival. A multicenter, single-arm, phase IV study was conducted in order to evaluate the efficacy and toxicity of frontline bevacizumab-based chemotherapy regimens in real life.

There are few therapeutic options for the treatment of metastatic gastric and gastroesophageal junction adenocarcinomas which fail front-line chemotherapy. A phase II multicenter study of second line nab-paclitaxel was conducted aiming to evaluate its efficacy and tolerance in patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. Thirty-nine patients (median age 62 years) with locally advanced inoperable and metastatic gastric and GEJ adenocarcinoma were enrolled. All patients had a PS of 0-1, 17 pts (43.6%) had prior surgery, 4 had received prior adjuvant chemotherapy, and 33 (84.6%) had receiver DCF in the first line setting. The median time from the prior treatment was 2.6 months (range, 1.0-13.8). Nab-paclitaxel was given weekly (125mg/m2, d1,d8, and d15 every 28 days). Partial response (PR) was achieved in nine pts (23.1%), disease stabilization (SD) in 11 (28.2%) and disease progression in 18 (46.2%) for an ORR of 23.1% (95% CI; 9.85-36.3) and a DCR of 51.3%. Responses were observed irrespectively of the prior administration docetxel-based chemotherapy. The median progression free survival was 3.0 months (95% CI 2.1-3.8) and the median overall survival 6.8 months (95% CI 0.7-8.8). Six (15.3%) pts developed grade 3/4 neutropenia, 7 pts (18%) grade 2/3 asthenia and 8 (20.5%) grade 2/3 neurotoxicity. Other AE were mild (grade <2). There was no treatment-related death but treatment discontinuation was required in 3 (7.7%) pts for probable treatment-related reasons. Second line nab-paclitaxed is an active and well tolerated treatment for patients with locally advanced inoperable/metastatic gastric and GEJ carcinomas even in pre-treated pts with a docetaxel-based regimen and merits further evaluation in the first-line setting.Tabled 1Demographic Data/ResponsesN%Response to treatmentCR/PR (ORR)923.1SD928,2Disease Control Rate (DCR)1851.3Time from prior treatment**Median (min-max)2.6 ( 0.2 – 13.8) Open table in a new tab

Objectives: To compare the activity and tolerance of the consecutive administration of four active chemotherapeutic agents in combination with bevacizumab to a bevacizumab- and platinum-based chemotherapy doublet as front-line treatment in patients with non-squamous NSCLC.Patients and methods: Patients with advanced/metastatic NSCLC, performance status of 0-2 and normal organ function were randomized to receive either 3 cycles every 3 weeks of cisplatin 80 mg/m(2) (day 1), oral vinorelbine 60 mg/m(2) (days 1 and 8) and bevacizumab 15 mg/1<g (day 1) every 3 weeks (VCB regimen) followed by 3 cycles of docetaxel (75 mg/m(2), day 1), gemcitabine (1100 mg/m(2), days 1 and 8) and bevacizumab 15 mg/kg (day 1) (DGB regimen) (arm A) or 6 cycles of cisplatin 80 mg/m(2), docetaxel 75 mg/m(2) and bevacizumab 15 mg/kg on day 1 (DCB regimen; arm B) every 3 weeks.Results: Thirty-eight and 39 patients were enrolled in arm A and B, respectively. The study did not meet its primary endpoint since, the ORR was 39.5% (95% CI: 23.9-55.0%; 1CR and 14 PR) and 46.2% (95% CI: 30.5-61.8%; 2 CR and 16 PR) in arm A and B, respectively (p = 0.554). There was no significant difference in terms of response duration (7.4 versus 4.7 months in arm A and B, respectively; p = 0.697), progression-free survival (5.8 versus 5.5 months, respectively; p = 0.540) and overall survival (16.9 versus 10.9 months; p= 0.390). No difference was recorded between the two arms regarding the toxicity profile. There were two drug-related deaths in arm B.Conclusion: Sequential therapy of VCB followed by DGB is a feasible and well-tolerated regimen but failed to show any superiority over the standard DCB regimen. (c) 2015 Elsevier Ireland Ltd. All rights reserved.

Intravenous gemcitabine is the standard of care for patients with metastatic cancer of the pancreas. Gemcitabine-based chemotherapy combinations, either doublets or triplets, have been tested in the past but have offered a small advantage (Brodoefel et al. in Eur J Radiol 73:594–600, 2010). In the present study, we present the results of the triplet gemcitabine–oxaliplatin–erlotinib combination as firstline treatment in this setting.

Introduction: Non-small-cell lung cancer (NSCLC) is very common in the elderly. Gemcitabine combined with platinum agents is among the optimal chemotherapy regimens for NSCLC treatment. In a previous phase I study conducted by HORG, the maximum tolerated doses of the biweekly gemcitabine plus carboplatin combination was determined in elderly patients with NSCLC.

Introduction: More than 50% of newly diagnosed cases of colorectal cancer (CRC) are observed in patients >65 years. Irinotecan-based combination chemotherapy prolongs survival in patients with mCRC.

Introduction: Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Platinum/gemcitabine doublet is considered an optimal chemotherapeutic regimen for NSCLC treatment; however, it has not been evaluated in the elderly. In a previous phase I study conducted by HORG, the maximum tolerated dose of the biweekly carboplatin/gemcitabine was determined in elderly patients with NSCLC.

Purpose: To assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E) in combination with bevacizumab (B) [DEB regimen] as front-line treatment in patients with metastatic breast cancer (MBC).Patients and methods: Women with previously untreated HER2-negative MBC received B (15 mg/kg), E (75 mg/m(2)) and D (75 mg/m(2)) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles followed by B (15 mg/kg q3w) until disease progression. Primary endpoint was the overall response rate (ORR). Circulating tumor cells (CTCs) were evaluated using the CellSearch system at different time points during therapy.Results: Eighty-three women were enrolled with median age 62 years, performance status 0-1 in 93%, triple negative disease in 12% and liver metastases in 47%. In an intention to treat analysis, complete response was achieved in 13 (15.7%) and partial response in 42 (50.6%) (overall response rate 66.3%; 95% CI 56.09-76.44%). The median time to progression was 20.1 months and the 1-year overall survival rate 82.3%. Grade 3-4 neutropenia occurred in 37%, febrile neutropenia in 10%, anemia in 4%, thrombocytopenia in 2% and diarrhea in 2% of patients. There were two deaths possibly related to study treatment (sigmoid perforation n = 1; sudden death n = 1). Moreover, one patient developed pulmonary embolism and another one myocardial infarction while on treatment. Although DEB administration significantly reduced the proportion of patients presenting CTCs, the detection of >= 5 or >= 1 CTCs before treatment initiation was significantly associated with worse progression-free survival (p = 0.001 and p = 0.004) and overall survival (p = 0.001 and p = 0.027), respectively.Conclusions: The DEB regimen is a very active but also potentially toxic combination in MBC. Detection of CTCs before treatment is associated with worse outcome. Clinicaltrials.gov:NCT00705315 (C) 2013 Elsevier Ltd. All rights reserved.

Background: Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Bevacizumab when added to cytotoxic chemotherapy in patients with NSCLC offers progression free survival (PFS) and overall survival (OS) benefit. However there are conflicting results about its role in older patients and has not been prospectively evaluated in elderly-specific trials. The purpose of the present study was to evaluate the activity of bevacizumab in combination with docetaxel as first-line treatment in older NSCLC patients, in the context of a phase II trial.

Purpose: To compare the efficacy of dose dense docetaxel versus paclitaxel following FEC as adjuvant chemotherapy in node positive early breast cancer. Patients and treatment: Women 18–75 years old with histologically confirmed HER2-negative invasive breast carcinoma surgically resected with at least one infiltrated axillary lymph node and absence of metastatic disease were randomized to receive 4 cycles of fluorouracil (700mg/m2), epirubicin (75mg/m2), cyclophosphamide (700mg/m2) followed by 4 cycles of either docetaxel (75mg/m2) or paclitaxel (175mg/m2). All chemotherapy cycles were administered every 14 days with G-CSF support. Stratification was based on menopausal status, number of involved nodes and hormone receptor expression. The primary endpoint of the study was to compare the disease-free survival (DFS) at 3 years and 239 patients were scheduled to enroll on each arm. Results: Between 2004–2007, 481 women were randomized and received FEC followed by docetaxel (arm A; n=240) or paclitaxel (arm B; n=241). The median age was 55 years in both arms, premenopausal status 31.3% versus 32.8%, more than 10 involved axillary nodes in 12.9% versus 12.4%, histological grade 3 tumor in 36.3% versus 35.3% and hormone receptor negative disease in 14.6% versus 12% of patients in arms A and B, respectively. After a median follow up of 56.3 and 55.6 months (p = 0.3) for arms A and B, respectively, there were 42 (17.5%) versus 47 (19.5%) disease relapses (p = 0.5) and 20 (8.3%) versus 22 (9.1%) disease-related deaths (p = 0.7), respectively. The 3-year DFS rates were 88.1% versus 87.3% for arms A and B, respectively. Toxicity included grade 2–4 neutropenia in 31% versus 21% (p = 0.01), thrombocytopenia 3.5% versus 0.8% (p = 0.06), febrile neutropenia 2.1% versus 1.2% (p = 0.5), diarrhea 3.7% versus 2.5% (p = 0.4), neurotoxicity 2.9% versus 4.6% (p = 0.3) of patients in arms A and B, respectively. There were no toxic deaths. Conclusion: The dose dense administration with G-CSF support of FEC followed by either docetaxel or paclitaxel as adjuvant chemotherapy in women with node positive early breast cancer is well tolerated and results in a similar 3-year DFS rate. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-09.

To compare the efficacy and safety of CAPIRI+bevacizumab (Bev) in comparison with FOLFIRI+Bev as first-line treatment for patients with metastatic colorectal cancer (mCRC). Patients were randomised to receive either FOLFIRI plus Bev 5 mg kg−1 every 2 weeks (Arm-A) or CAPIRI plus Bev 7.5 mg kg−1 every 3 weeks (Arm-B). Three hundred thirty-three patients (Arm-A=167; Arm-B=166) were enrolled into the study. No difference was observed in median progression-free survival (PFS) (10.0 and 8.9 months; P=0.64), overall survival (25.7 and 27.5 months; P=0.55) or response rates (45.5 and 39.8.7%; P=0.32) for FOLFIRI-Bev and CAPIRI-Bev, respectively. Patients treated with CAPIRI-Bev presented significantly higher incidence of diarrhoea (P=0.005), febrile neutropenia (P=0.003) and hand–foot skin reactions (P=0.02) compared with patients treated with FOLFIRI-Bev. Treatment delays (P=0.05), dose reduction (P<0.001) and treatment discontinuation owing to toxicity (P=0.01) occurred more frequently in the CAPIRI-Bev arm. The PFS of FOLFIRI-BEV is not superior to that observed with the CAPIRI-Bev regimen. CAPIRI-Bev has a less favourable toxicity profile, requiring dose reductions, in order to be considered as an option in first-line treatment of patients with mCRC.

44 Background: To evaluate the efficacy and safety of FOLFIRI plus CRT with 5FU as adjuvant treatment for patients with OGC. Methods: Patients received treatment with FOLFIRI (irinotrecan 150 mg/m2, d1, LV 200 mg/m2, d1+2 and 5FU [400 mg/m2/d bolus and 600 mg/m2/d, 22 h infusion, d1+2]) for 2 15-day cycles followed by RT (45Gy) with 5FU continuous infusion (325 mg/m2/d in the 1st and 5th week) administration. Eight additional cycles of FOLFIRI were administered after the completion of CRT. BRCA1, ERCC1, XPD, TOPO-I, TOPO-IIA and B and TS mRNA expression was determined in the primary tumor where available. Results: The median age of the 171 enrolled patients was 62 years, 114 (66%) were males, 136 (79%) had R0 resections and 152 (89%) had at least a D1 resection. Treatment was completed as per protocol in 107 (63%) of the patients. CRT was completed in all but 5 (3%) patients. The median rate of drug exposure was 93% for irinotecan, 87% for 5FU and 91% for LV. The most common grade 3/4 adverse events were neutropenia (32%), febrile neutropenia (3.5%) and diarrhea (7%). After a median follow-up of 45.7 months 84 had relapsed and 70 were deceased. The median disease-free survival (DFS) was 30 months (95% CI: 18-41 months), while the projected median overall survival (mOS) was 53.7 months (95% CI: 30-77 months). The recurrence free probability at 5 years was 44% while the probability of survival at 5 years was 46%. From the studied pharmacogenetic markers only TS low expression was correlated with a trend towards improved DFS and OS in patients with R0 resections. Conclusions: These results show that the administration of FOLFIRI plus CRT with 5FU as adjuvant treatment in OGC is a feasible approach with acceptable toxicity and challenging efficacy which merits further evaluation in a randomized trial. No significant financial relationships to disclose.

1116 Background: Docetaxel (D) plus epirubicin (E) is highly active first-line therapy for metastatic breast cancer (MBC), with acceptable toxicity profile. The addition of bevacizumab (B) was investigated in this phase I-II study to assess the efficacy and toxicity of front-line DEB in MBC patients. Methods: Women with previously untreated HER2-negative MBC received B (15 mg/kg), E (75mg/m2) and D (75mg/m2) with prophylactic G-CSF support every 3 weeks for 6 cycles followed by B (15 mg/kg q 3w) until disease progression with primary end point objective response rate (ORR). Circulating tumor cells (CTCs) were measured in the blood using the CellSearch system before and at different time points after therapy. The study followed a two step design with toxicity and efficacy initially assessed in the first 16 patients. Results: Sixty-four women were enrolled with median age 60 years, performance status 0-1 in 92%, triple negative 11%, liver metastases 48%. In sixty evaluable patients complete response was observed in 10 (17%), partial response in 28 (47%) with ORR 64%. Estimated median time to progression was 14 months and 1 year survival 82%. Grade 3-4 neutropenia occurred in 34%, febrile neutropenia in 8%, anemia in 5%, thrombocytopenia in 3%, diarrhea in 3% of patients. There were two deaths possibly related to study treatment (sigmoid perforation n=1; sudden death n=1). In 50 patients with detectable CTCs prechemotherapy, 14 (28%) had >5CTCs/7.5ml blood and in 10 of them (71%) CTCs decreased to <5 after the first cycle. Conclusions: The DEB is an active but also potentially toxic combination in MBC and is associated with a significant decrease of the number of CTCs. No significant financial relationships to disclose.

Background: A subgroup analysis of oxaliplatin (LOHP) + irinotecan (CPT-11) + 5-fluorouracil (5FU) and leucovorin (LV) (FOLFOXIRI regimen) versus irinotecan + 5FU/LV (FOLFIRI regimen) as first-line treatment of patients >65 years old with metastatic colorectal cancer is presented.Patients and Methods: Eighty-two (56%) and 75 (55%) patients with metastatic colorectal cancer aged >65 years were enrolled in the FOLFOXIRI and FOLFIRI regimen, respectively.Results: There was no statistically statistical difference in terms of overall survival or time-to-tumor progression between young and aged patients between the two chemotherapy arms. The objective response rate was significantly lower in older patients treated with FOLFOXIRI (32% vs. 52%; OR: 1.45, 95% CI: 1.06-2.09; p=0.03). Elderly patients experienced a significantly higher incidence of grade 3/4 diarrhea compared to younger patients, irrespectively of the chemotherapy regimen (p = 0.005 for FOLFIRI; p = 0.017 for FOLFOXIRI). Dose reductions and treatment delays were more frequent in the FOLFOXIRI arm.Conclusion: FOLFOXIRI does not seem to offer substantial benefit compared to FOLFIRI regimen in elderly patients with metastatic colorectal cancer. (C) 2009 Elsevier Ireland Ltd. All rights reserved.