656 Background: Randomized clinical trials have established new chemotherapeutic standards of care for metastatic pancreatic cancer, namely FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GNP) after demonstrating a significant and relevant increase of overall survival. However, there are some important uncertainties regarding how many patients are candidate to each of the two new regimens in the real life and how is the pattern of use in the elderly population. Methods: This is a retrospective study. Departments of Pharmacy of 7 Spanish hospitals generated the listings of patients (pts) treated in first line with these new regimens (FFX or GNP). Non-metastatic patients were excluded. An exploratory analysis was performed in the elderly population. Results: From Jan 2012 to Dec 2017, a total of 119 pts (M/F 58/42 %) were treated. Med age 63 y (38-83 y), 99% adenocarcinoma. 40% located in the head of pancreas. ECOG 87% 0-1. 89% had liver mets. In the 1st line 49.6% were treated with FFX and 50.4% with GNP. 53% of the pts could receive a 2nd line (82% after FFX 75% after GNP). The median OS was 12 months with no statistically significant differences between both regimens (12,7m for FFX vs 10,2 m for GNP). Elevated Ca 19.9 levels and Neutrophil-Lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70 yo. 13 (41%) were treated with FFX and 19 (59%) with GNP. The median OS for patients older than 70 was 9.5m versus 12.3m for patients younger than 70. Conclusions: In our setting the use of FFX and GNP for treating metastatic pancreatic cancer is quite similar. Superiority could not be demonstrated for any of the schemes in first-line. Overall survival was determined by basal Ca 19.9 and NLR. Patients receiving both regimens (FFX or GNP) in first/second line whichever the sequence, exhibited the best survival rates. In our series elderly patients had poor survival rates.

Background: This multicentre, randomised, and phase II study evaluated mFOL-FOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). Patients and methods: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. Results: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2: 1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]< 0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade >= III AEs: 70%/68%). The most common grade >= III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade >= III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). Conclusion(s): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients. (C) 2018 Elsevier Ltd. All rights reserved.

Background: Nab-P+G significantly improved overall survival versus G in Patients (P) with Karnofsky index ≥70% metastatic PDAC (Von Hoff et al, 2013). The aim of this study was to select a tolerable dose -schedule of nab-P+G (Ph I), and to evaluate the efficacy of the selected regimen (Ph II) in patients with previously untreated ECOG-2 advanced PDAC. Methods: In the phase1 portion of the study patients were randomized to one of 4 treatment regimens including G 1000 mg/m2 and nab-P 150 mg/m2 (arm B) or 125 mg/m2 (arm D) days 1 and 15 every 28 days or same dose of G and nab-P 100 mg/m2 (arm C) or 125 mg/m2 (arm E) days 1, 8, and 15 every 28 days. The two safest regimens determined by analyzing hematological and non-hematological grade 3-4 toxicity, 30 and 60 days mortality, treatment discontinuation due to toxicity and dose intensity were selected for evaluation in the phase 2 portion of the study with 6 months overall survival (OS) as the primary endpoint. Results: Regimens arm C and arm E (days 1, 8, 15 every 28 days schedule) were selected for the phase 2 portion of the study. A total of 221 patients (111 in arm C/110 in arm E) were enrolled. Median age was 71/68 y, 51/55% were male and 91/83% had metastatic disease (liver 63/62%). Most frequent grade 3-4 toxicity per arm were anemia (12/7%), neutropenia (32/30%), thrombocytopenia (7/11%), febrile neutropenia (3/4%), asthenia (14/16%) and neurotoxicity (11/16%). There were no significant differences in 6 months OS 63/69%, response rate (RR) 24/28% and median progression free survival (PFS) 5.7/6.7 months respectively in each arm. Conclusions: Nab-P in combination with G, both at 100 and 125 mg/m2 dose administered on a standard schedule of days 1, 8 and 15 is well tolerated and results in acceptable OS, RR and PFS in this fragile patient population. Clinical trial identification: NCT02382263 EudraCT: 2012-003605-97 Legal entity responsible for the study: PH Research Funding: Celgene Disclosure: M. Hidalgo: Honoraria: Celgene. Consulting or advisory role: Celgene. Research funding: Celgene. Travel, accomodations: Celgene. R. Pazo-Cid: Consulting or advisory role: Celgene, Baxalta. A. Muñoz: Consulting or advisory role: Celgene. J. Sastre: Consulting or advisory role: Amgen, Sanofi, Bayer, Boheringer. Travel accomodations: Merck. Researcha funding: Amgen, Merck. All other authors have declared no conflicts of interest.

Background: UPTR remains controversial in the initial management of unresectable asymptomatic mCRC patients (pts), whereas right sidedness is a bad prognostic factor. Methods: Retrospective pooled analysis of KRAS WT mCRC pts treated with 1st line EGFR inhibitors (EGFRI) + chemotherapy (CT) from two phase II randomised trials (MACRO-2 & PLANET). We analysed UPTR effect on overall survival (OS) and progression free survival (PFS) by tumour sidedness (right/left) and stage (I-III/IV) at diagnosis. All stage I-III pts underwent UPTR at diagnosis as standard procedure. Results: 260 pts were included in the analysis (Table). In pts with stage IV at diagnosis, UPTR was associated with a better OS, although differences were only significant in right sided tumours (mOS (m): 20.9 vs 10.6; HR non-UPTR vs UPTR 2.1 (1.0, 4.3); P = 0.038). Conversely, left sided tumours had a significantly better OS vs right sided tumours regardless of UPTR: UPTR HR 0.4 (0.2, 0.8); P = 0.006; no UPTR HR 0.2 (0.1, 0.4); P < 0.0001. In pts with stage I-III at diagnosis (all UPTR), there were no differences in OS according to sidedness. After UPTR, OS was significantly higher in stage I-III tumours vs stage IV only in right sided tumours. Similar results were observed for PFS.Table492PRightLeftUPTRNo UPTRUPTRNo UPTRStage I-III at diagnosis, N931OS(m)34.928.9(30.6 -)(17.6 -)HR left vs right1.5 (0.6, 4.1)p0.430PFS(m)14.310.8(8.5, 19.8)(7.6, 13.9)HR left vs right1.7 (0.7, 4.2)p0.281Stage IV at diagnosis, N182478100OS(m)20.910.636.926.5(5.9, 34.2)(6.3, 11.8)(25.3, 45.8)(20.7, 32.0)HR No UPTR vs UPTR2.1 (1.0, 4.3)1.4 (1.0, 2.0)p0.0380.088UPTRHR left vs right0.4 (0. 2, 0.8)p0.006HR Stage IV vs Stage I-III4.4 (1.4, 13.9)1.0 (0.6, 1.8)p0.0190.931No-UPTRHR left vs right0.2 (0.1, 0.4)p<0.0001PFS(m)7.24.09.99.8(1.9, 14.8)(3.5, 6.5)(7.4, 12.8)(8.4, 11.7)HR No UPTR vs UPTR2.36 (1.0, 5.6)1.02 (0.7, 1.5)p0.0490.932UPTRHR left vs right0.6 (0.3, 1.2)p0.123HR Stage IV vs Stage I-III3.5 (1.1, 11.1)1.1 (0.7, 1.8)p0.0360.745No-UPTRHR left vs right0.27 (0.2, 0.5)p<0.0001 Open table in a new tab Conclusions: In mCRC KRAS WT pts treated in 1st line with EGFRI + CT, UPTR seemed to improve outcomes particularly in right sided tumours. Table: 492P Median (95%CI) OS and PFS Clinical trial identification: MACRO-2 trial: NCT01161316 - PLANET trial: NCT00885885 Legal entity responsible for the study: Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) Funding: Amgen S.A. (PLANET) and Merck. S. L. (MACRO-2) Disclosure: M. Valladares-Ayerbes: Consultant or advisory relationship and honoraria: Roche, Amgen, Merck Serono. A. García-Tapiador: Consultant or advisory role and honoraria: Merck. E. Aranda Aguilar: Advisory role from Amgen, Bayer, Celgene, Merck, Roche, Sanofi. All other authors have declared no conflicts of interest.

Aim: The optimal duration and content of first-line therapy in p with mCRC once they have achieved the maximal response remains controversial. This multicenter, randomized, phase II study was aimed to evaluate the efficacy and tolerability of 8 cycles of mFOLFOX plus C followed by maintenance mFOLFOX plus C or s/a C.

ABSTRACT Introduction Standard chemotherapy is increasingly discontinued after successful “induction” in patients (pts) undergoing 1st line treatment for mCRC. MGN1703 is a synthetic DNA-based immunomodulator acting as an agonist of TLR-9 that has shown preclinical activity in mCRC. This study has been conducted to assess clinical efficacy, immunogenicity, and safety of MGN1703 as maintenance vs. placebo. Methods The IMPACT study is an international, multicenter, randomized double-blind placebo-controlled phase II/III study. Pts with mCRC showing disease control (CR, PR or SD) after 4.5 to 6 months of 1st-line standard therapy with FOLFOX/XELOX or FOLFIRI +/- bevacizumab (investigatoŕs choice) were included. Results Interim analysis of the unblinded data revealed a strong therapeutic effect compared to anticipated PFS. Therefore, patients were withheld from further randomization, according to a decision of the steering committee. In the ITT population (N = 55 pts), hazard ratio (HR) was 0.53 in favor of MGN1703 (p = 0.062). In the per-protocol population (excluding screening failures; N = 50), HR was 0.43 (p = 0.015). In the pre-defined target population (2 out of 3 factors: CEA Conclusions Maintenance therapy with MGN1703 after standard chemotherapy with or without bevacizumab, is associated with significantly improved progression-free survival compared to placebo and is accompanied by low toxicity. A confirmatory clinical study in patients with metastatic CRC is currently being planned. Disclosure M. Tschaika: Employment, stock ownership. M. Schmidt: Employment. B. Wittig: Stock ownership. All other authors have declared no conflicts of interest.

Background KRAS mutation is present in approximately 35-40% of patients with metastatic colorectal cancer (mCRC) and has been established as a predictive marker of resistance to anti-EGFR therapy, but its role as prognostic factor is not yet clear. This study is aimed to analyze the prevalence and the impact in prognosis of expanded number of KRAS mutations in caucasian mCRC population and the sensitivity of the TaqMelt PCR assay cobas KRAS Mutation Test. Methods A single institution retrospective cohort of 669 consecutive mCRC patients between 2000-9 with clinical follow-up was studied for frequent 7 mutations in codons 12/13 by ARMS-scorpion real-time PCR (Therascreen, Qiagen) and TaqMelt PCR assay cobas KRAS Mutation Test (Roche), which are designed to detect 19 mutations in KRAS codons 12, 13 and 61. DNA was obtained by cobas DNA preparation kit (Roche) from one single 5um FFPE tissue section and by QIAamp DNA FFPE Tissue Kit (Qiagen) from 50um of tissue. Results KRAS mutation was detected by the cobas KRAS Mutation Test in 41.2% of mCRC patients and was correlated with poor overall survival (OS) (p = 0.013), OS from the metastatic diagnosis for metachronous disease (p = 0.025), disease-free survival for metastatic disease (p = 0.012) and time to progression (p = 0.046). KRAS mutation was significantly associated with tumor grade (p = 0.025) and liver as first site of dissemination (p = 0.047). However, KRAS mutations detected by Therascreen did not impact on prognosis. The median of DNA concentration obtained by cobas and QIAamp was 120ng/ul and 80ng/ul, respectively. The frequency of invalid cases was 5.7% (cobas) and 17.9% (Therascreen). Finally, cobas identified 19.2% additional KRAS mutations not detected by Therascreen. Next Generation Sequencing by 454 GS FLX+ System analysis is ongoing to validate discrepant mutations. Conclusions The cobas KRAS Mutation Test is a robust and reproducible assay that, 1) obtains superior DNA recovery from very small amount of FFPE tissue; 2) detects up to 19.2% of mutations not detected by other methods; and, 3) KRAS mutations detected by cobas correlate with poor outcome in mCRC. Disclosure All authors have declared no conflicts of interest.

e18070 Background: Topotecan IV at dose of 1.5 mg/m2 days 1 –5 every 3 weeks is the standard treatment for pretreated SCLC pts. Weekly topotecan at dose of 4 mg/m2 has shown an excellent toxicity profile. Based in previous studies of our group using gemcitabine doublets in pretreated SCLC pts, we conducted a prospective phase II study to determine the activity of this combination in this population. Methods: Pts were eligible if they had measurable or evaluable disease, previous treatment with platins, adequate hepatic, renal and bone marrow function. Topotecan dose was 4 mg/m2 IV days 1 and 8, and gemcitabine 1,250 mg/m2 (30-minute IV infusion) days 1 and 8 every 3 weeks. Results: 58 pts were enrolled, 54 male and 4 female. Median age was 61 years (range 39- 83); 92% had PS 0 or 1; 38 pts had sensitive disease and 20 pts had refractory disease. The median of cycles per patient was 3 (range 1-3). All the pts were evaluable for efficacy and toxicity. In an intent to treat analysis the response rate was 12% (95% CI: 5%-23%), 1 patient with sensitive disease achieved a complete response (1.7%). 21% of pts showed stable disease and 67% progression. Median time to progression was3 months (95% CI: 2-4 m) and median survival 5 months (95% C.I: 3-7 m). Toxicity was very mild with grade 3-4 hematological toxicity in 17% of patients, without non-hematological grade 3-4 toxicity. 2 patients developed skin toxicity grade 1-2. Conclusions: Weekly topotecan- gemcitabine does not seem to improve the efficacy of the standard schedule of IV topotecan in monotherapy. The tolerability is acceptable. In our opinion further development of this combination is not warranted. No significant financial relationships to disclose.