No abstract

The involvement of GALNT12 in colorectal carcinogenesis has been demonstrated but it is not clear to what extent it is implicated in familial CRC susceptibility. Partially inactivating variant, NM_024642.4:c.907G>A, p.(D303N), has been previously detected in familial CRC and proposed as the causative risk allele. Since phenotypes of the described carrier families showed not only CRC but also a polyp history, we hypothesized that GALNT12 could be involved in adenoma predisposition and consequently, in hereditary polyposis CRC syndromes. For that purpose, we have screened the GALNT12 gene in germline DNA from 183 unrelated attenuated polyposis patients. c.907G>A, p.(D303N) was detected in 4 cases (MAF = 1.1%) and no other candidate variants were found. After segregation studies, LOH analyses, glycosylation pattern tests and case-control studies, our results did not support the role of c.907G>A, p.(D303N) as a high-penetrance risk allele for polyposis CRC.

BackgroundThe impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice.MethodsData on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle.ResultsAdverse event (AE) management was consistent with the Guidelines as a whole for 28.7 % out of 966 post-implementation cycles compared with 23.1 % out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33 % pre-implementation vs. 44.5 % post-implementation cycles; p < 0.0001), diarrhea (74.0 % vs. 80.5 %; p = 0.011) and dyslipemia (25.0 % vs. 44.6 %; p < 0.001).ConclusionsSlight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction.

TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they are added in first and second-line in L-sided CRC. The conflicting results in anti-VEGF vs. anti-EGFR studies (FIRE-3, PEAK and CALGB/SWOG 80405 studies) suggest that the sequence of targeted therapies added to FOLFOX or FOLFIRI regimens in first- and second-line treatment could be an important factor in the overall survival (OS) of mCRC patients. Currently, there are no randomized data on the sequential use of an anti-EGFR followed by an anti-VEGF or vice versa. Therefore, the aim of this randomized clinical trial is to compare the efficacy of two treatment sequences, panitumumab followed by bevacizumab versus bevacizumab followed by panitumumab in combination with FOLFOX chemotherapy in first-line and with FOLFIRI in second-line in patients with wild-type RAS, primary L-sided, metastatic colorectal cancer (mCRC). Methods: A phase III, multicentre, open-label and randomized two-arm clinical trial. Untreated patients with wild-type RAS mCRC (determined locally), primary L-sided and unresectable will be screened for this trial. Eligible patients will be randomized 1:1 to receive first-line (1L) panitumumab plus FOLFOX and then bevacizumab plus FOLFIRI as second-line (2L) treatment (Seq. 1) or bevacizumab plus FOLFOX as 1L and then panitumumab plus FOLFIRI as 2L treatment (Seq. 2). Randomization will be stratified by number of metastatic organs involved (1 vs > 1). Primary objective is the comparison of the progression free survival (PFS) rate at 35 months (m) of Seq 1 vs Seq. 2. Secondary objectives: PFS from randomization to 2nd progression or death, OS rate at 35 months and OS of Seq. 1 vs Seq. 2; PFS, objective response rate, disease control rate, early tumour shrinkage, Depth of Response, duration and time to response and safety in 1L treatment and in 2L treatment in each Sequence arm. Exploratory objectives: impact of baseline biomarkers predictive of the efficacy in each Sequence arm and the clinical impact of clonal dynamics by longitudinal analysis of circulating tumour deoxyribonucleic acid (ctDNA) in plasma. The trial is in progress; 28 of up to 370 planned patients have been recruited at the end of January 2019 (first patient in 31 October 2018). Clinical trial information: NCT03635021.

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.