J.M. Cano

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background:To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy.Methods:Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrells c-index was used to evaluate discrimination.Results:The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351).Conclusions:We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry

Background:The choice of chemotherapy in HER2-negative gastric cancer is based on centre’s preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).Methods:We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2–3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of ‘treatment-by-histology’ interaction, was used to estimate treatment effect.Results:Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525–0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054–1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49–0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50–0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46–0.88), P=0.046.Conclusions:As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

1452PMULTIDISCIPLINARY TREATMENT OUTCOME OF DESMOID-TYPE FIBROMATOSIS (DTF). A REGISTRY-BASED STUDY FROM SPANISH GROUP FOR RESEARCH ON SARCOMA (GEIS)

ABSTRACT Aim: We analyzed retrospectively data about treatment outcome with existing treatments in DTF. Methods: Descriptive analysis of data related to diagnosis and treatment from all DTF was collected in patients (p) between Sept. 1999 and Nov. 2013 in 26 hospitals of GEIS . Ethics committee approval was obtained. Results: 185 patients. Age: median 37 years (6-85) .63.2% female .Median time lapse from first symptom to diagnosis: 4 months(m). Location : trunk wall 81p (43.8%), extremities 50p (27%), retroperitoneum 10p (5.4%), Gastro-intestinal 16p (8.6%), Head/neck 6p( 3.2%), others 6p(3.2%), 2p (1.1%) missing . 20p (11%) presented a second neoplasia (throughout the whole process). Median tumor size: 8 cm(range 1-96). 3 p (1.6%) presented distant peritoneal disease. First treatment : No treatment 6p (2.7%), Surgery (S) alone 144 p ( 77.8%, 3p >1), S+radiotherapy (RT) 7p (3.7%), S+ chemotherapy (CT) 2 p (1.08%), S+hormonetherapy (HT) 3p (1.62%), S +HT+ Non steroidal antiinflammatory drug (NSAID)+Tirosin-kinasa inhibitor(TKI) 1p (0.54%), CT 5p (2.7%), RT 3p ( 1.6%),NSAID 5p (2.6%), HT 2p (1.08%), TKI 1p(0.54%), HT+NSAID 6p (2.7%). 128p (69.2%) became free of disease, in 49p (26.5%) residual disease remained . 61p (33%) progressed. Median Progression free survival (PFS) :109 m (95%CI 44.6-175.1).Multivariate analysis for PFS: extended/radical surgery(p=0.000) and tumor size Response to CT /other treatments CT treatment Other treatments (TKI, HT, NSAID) p % p % PR 12 30.7 4 7.4 SD 15 38.4 31 55.3 PD 3 7.6 10 17.8 NE 4 10.2 6 10.7 NA 5 12.8 5 8.9 Total 39 100 56 100 PR: partial response; SD: stable disease; PD: progressive disease; NE: non evaluable; NA: non available data. Conclusions: Surgical quality and tumor size seems to play a relevant role in predicting PFS in DFT. Other sistemic treatments showed meaningful activity in progressive disease. Disclosure: All authors have declared no conflicts of interest.

Efficacy and safety of chemotherapy in older versus non-older patients with advanced gastric cancer: A real-world data, non-inferiority analysis.

OBJECTIVE Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC. MATERIALS AND METHODS We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008-2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥70 vs.<70years. The fixed-margin method was used (hazard ratio [HR]<1.176) that corresponds to conserving at least 85% efficacy. RESULTS 33% (n=489) of the cases analyzed were ≥70 years. Two-agent chemotherapies and combinations with oxaliplatin (48% vs. 29%) were used more often in the older patients, as were modified schedules and/or lower doses. Toxicity grade 3-4 was comparable in both groups, although when looking at any grade, there were more episodes of enteritis, renal toxicity, and fatigue in older patients. In addition, toxicity was a frequent cause for discontinuing treatment in older patients. The response rate was similar in both groups. After adjusting for confounding factors, the non-inferiority of OS associated with schedules administered to the older vs. younger subjects was confirmed: HR 1.02 (90% CI, 0.91-1.14), P (non inferiority)=0.018, as well as progression-free survival: HR 0.97 (90% CI, 0.87-1.08), P(non-inferiority)=0.001. CONCLUSION In this AGC registry, the use of chemotherapy with schedules adapted to patients ≥70 years provided efficacy that was not inferior to that seen in younger cases, with comparable adverse effects.

CP-165 Efficacy and toxicity of combined chemotherapy with platinum and fluoropyrimidine in gastric cancer: Agamenon study cohort

Background There is no one regimen considered standard for advanced gastric cancer. Platinum and fluoropyrimidine are the most consolidated for use as firstline palliative chemotherapy. Purpose To compare the effectiveness (response rate (RR), progression free survival (PFS), overall survival (OS)) and tolerability of platinum and fluoropyrimidine based regimens for untreated advanced gastric cancer. Material and methods AGAMENON is a multicentre, non-interventional, observational study. Eligibility criteria included the use of chemotherapy with platinum plus fluoropyrimidine for untreated advanced HER2 negative gastric adenocarcinoma between 2008 and 2015. The Kaplan-Meier and log-rank methods were used to estimate PFS and OS. The Concordance Index was applied to evaluate discriminatory capacity. Results This analysis comprised 254 eligible patients from 946 registered. Baseline characteristics were: ECOG performance status 0–1, 78.7%; male, 67,3%; median age, 65,7 years; two or more chronic comorbidities, 19.3%. The most common tumour location was the body of the stomach (30.7%). 48.4% of patients had an intestinal Lauren type and 16.1% had three or more sites of metastatic disease. 106 patients received cisplatin containing chemotherapy (5-fluorouracil/cisplatin in 16.0%, cisplatin/capecitabine in 90.0%). 148 patients received oxaliplatin alternatives (5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) in 54.7%, oxaliplatin/capecitabine (CapeOX) in 45.27%). The median months of treatment was 4 for all regimens and drugs. Toxicity was reposted as the reason for discontinuation in 7.7%, 6,8%, 11.1% and 26.7% for fluorouracil, capecitabine, cisplatin and oxaliplatin, respectively. The average dose intensities of 5-fluorouracil, capecitabine, cisplatin and oxaliplatin were 0.96, 0.85, 0.93 and 0.98, respectively. The response rate was 40.2%, median PFS was 5.8 months (95% CI 5.3 to 6,4) and median OS was 10.9 months (95% CI 9.7 to 12.5). Grade 3–4 toxicities included: neutropenia (15.4%), emesis (3.9%), diarrhoea (3.9%), neuropathy (2.8%), anaemia (2.0%), hand-foot syndrome (1.6%) and thrombocytopenia (0.4%). The most frequent grade 1–2 toxicities were: anaemia (50.4%), neuropathy (46.1%), hand-foot syndrome (28.4%), emesis (28.0%), neutropenia (26.8%), diarrhoea (24.4%) and thrombocytopenia (20,5%). There were 40 toxicity treatment or tumour related inpatients. Conclusion These outcomes are consistent with the efficacy and toxicity data from phase III and II clinical trials (ML17032 study, Ann Oncol 2009; Al-Batran S, et al. J Clin Oncol 2006). In the AGAMENON study, different combinations of platinum and fluoropyrimidine showed similar benefit in clinical practice. References and/or Acknowledgements The investigators of the AGAMENON study. No conflict of interest.

1453PSOLITARY FIBROUS TUMOR (SFT): A REGISTRY PROGRAM TO ASSESS FREQUENCY AND MANAGEMENTE IN OUR COUNTRY. A SPANISH GROUP FOR RESEARCH ON SARCOMA (GEIS) STUDY

ABSTRACT Aim: SFT are soft tissue sarcomas with low incidence and intermediate biological potential behavior. The main aim of this observational study is to get new insights in clinical presentation, biological behavior and therapeutic approaches of SFT in our country. Methods: A web-based registry was built to collect diagnostic and therapeutic processes in patients (p) with SFT diagnosed in 22 centers (centers of reference and secondary centers) involved in this program. Median progression-free survival (PFS) and overall survival (OS), were estimated by Kaplan-Meier method. Ethics committee approval was obtained. Results: Between September 1999 and November 2013, 163 p (median age 52 years, 52.8% females, 88% had Karnofsky≥80%) were diagnosed. 12 p lacked some relevant data after diagnosis. 7 hospitals included 70% of cases. Primary tumor location was: 24% extremities and trunk-wall, 15% lungs, 13% pleural, 13% head and neck, 14% retroperitoneum and 2.5% meningeal sites. Excisional biopsy and core-biopsy were the method of diagnosis in 65% and 22% of p respectively. Median size was 8.6 cm (range 1-29). 11 p were metastatic at diagnosis. Initial treatment was surgery in 89% of 151 p, followed by adjuvant treatment in 23: 2 chemotherapy (CT), 15 radiotherapy (RT), 5 CT and RT, and 1 radiosurgery. The remaining p received: 1 CT, 2 RT, 1 sunitinib and 2 palliative care. 36 p progressed: 19 p could be resected. Antiangiogenic therapy was used in advanced disease:13 p received sunitinib (5 first line, 3 second line and 5 further lines), 5 p temozolamide-bevacizumab (3 first line and 2 further lines) and 2 p pazopanib (1 first line) . Sunitinib showed clinical benefit (CB) in 8 cases (35, 36, 30, 22, 8, 5, 4 and 2 months of duration), 4 progressions (PR) and 1 unknown. 2 p stopped for toxicity grade III-IV. Temozolamide-bevacizumab experienced CB in 3 cases (30,12, and 6 months of duration), 1 PR and 1 p stopped for toxicity grade III. 1p progressed with pazopanib and 1 was not evaluated for response. Median PFS was 5 years and median OS was not reached. OS and PFS at 10 years were 70% and 50% respectively. Conclusions: SFT are tumors that appear in different localizations, where radical surgery is the treatment of choice. In advanced disease, antiangiogenic therapy could provide longer CB in 60% of progressing cases. Studies with these drugs in advanced SFT are guaranteed. Disclosure: All authors have declared no conflicts of interest.

430PGEINOFOTE: SAFETY AND ACTIVITY ANALYSIS OF THE USE OF FOTEMUSTINE (FT) IN DIFFERENT SCHEDULES IN PROGRESSIVE GLIOBLASTOMA (GB) IN SPAIN

ABSTRACT Aim: Previous studies showed that FT may be useful as treatment in recurrent GB. The present study evaluate the activity and toxicity of FT in recurrent malignant GB patients in the clinical setting in Spain. Methods: Patients (age >18 years) with GB that was progressive (first or second recurrence) after prior standard radiotherapy plus temozolomide (TMZ) chemotherapy were eligible for the study. Patients were scheduled to receive FT in different schedules (Addeo vs others). Tumor response was assessed by MRI every 8-12 weeks. The primary end point was safety; secondary points included progression free survival (PFS), overall survival (OS). We analyze the differences between Addeo schedule (A) vs others (O) and 1° recurrence (1°R) vs 2° recurrence (2°R) in terms of safety and activity. Results: 84 patients were assessed; all of them began FT previously Nov 31, 2012. There were 46 males, and the median age was 56 years (ranged from 30 to 73). The median KPS was 70 (40-100). A schedule was used in 60 pts (71.4%). FT in first recurrence was used in 39 pts (46.2%) and 45 pts (51.2%) in second recurrence. The median PFS was (A 1°R / O 1°R/ A 2°R / O 2°R) 3.11/2.41/3.04/2.84 months, the median OS was (A 1°R / O1°R/ A 2° R / O 2°R) 6.15/5.29/4.36/3.87 months . The most common toxicities include thrombocytopenia and neutropenia. There were no statistical differences in Grade III or IV toxicities in relation with the type of schedule (A vs O) nor the 1° or 2° R (17%-7%). The patients received more frequent A schedule than O in 1°R or 2° R. No differences between A vs O in terms of clinical benefit, PS improve or less dexametasone use. Time to response: patients in A schedule spent less time to get the better response than patients with O schedules, whenever we use FT (no significant differences). Conclusions: FT has modest activity for recurrent GB with acceptable toxicity, regardeless the type of schedule. Probably, A get better response in less time than O schedules. Disclosure: All authors have declared no conflicts of interest.