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2669 Background: An early crossing of the Kaplan-Meier overall survival curves in randomized clinical trials (RCTs) comparing ICI alone to standard treatments has been observed across different cancer types, suggesting the existence of an excess of mortality upon ICI. Whether ED reflects the natural history of the disease or it is a treatment specific phenomenon remains unclear. Therefore, we conducted a metanalysis of RCTs to analyze the association of ICI treatment with ED. Methods: PubMed, Embase and Cochrane were searched (until 12/2021) for RCTs comparing 1st-line PD-1/PD-L1 inhibitors +/- CTLA-4 inhibitors (ICI-only group) or the same drugs in combination with other non-ICI therapies (ICI+OT group) (experimental arms) vs non-ICI treatments (control arm) in patients (pts) with advanced solid cancers. ED was defined as death within the first 3 months of treatment. RCTs providing the number of pts in the intention-to-treat (ITT) population who were alive within 0-3 months from randomization were considered eligible. Primary outcome was ED rate both in the ICI-only and in the ICI+OT groups vs control arm. Secondary outcome was to compare ED risk between ICI-only group and ICI+OT group. Further analysis according to PD-L1 level were performed. The ED rates were estimated by risk-ratio (RR) with 95% confidence intervals (CI) and pooled by random effect model. Heterogeneity was assessed by I2 statistics. Results: 56 RCTs (n = 38697 pts) were eligible, 48.2% included pts with thoracic malignancies. In the ICI-only group (18 RCTs, n = 6638 pts) 50.5% of pts received anti-PD-1/PD-L1 monotherapy and 43.4% anti-PD-1/PD-L1 + anti-CTLA-4 agents. In the ICI+OT group (43 RCTs, n = 15421 pts) 80.1% of pts received ICI + chemotherapy. Compared to control arm, risk of ED was significantly higher for pts who received ICI-only therapies (RR 1.27, 95% CI 1.04-155, p = 0.02, I2: 73%), but significantly lower in ICI+OT group (RR 0.80, 95% CI 0.71-0.89, p < 0.00001, I2: 36%). Risk of ED was also significantly higher with ICI-only compared to ICI-OT (RR 1.59, 95% CI 1.26-2.00). ED risk was higher upon ICI-only also in pts with high PD-L1 expression (TPS ≥50%, TC or IC 3, CPS ≥10) and, after excluding Keynote-024, this result became statistically significant (7 RCTs, RR 1.54, 95% CI 1.13-2.10, p = 0.007) with I2 reducing from 63 to 46%. Conclusions: Across cancer types ED is a treatment specific phenomenon, increasing with first-line anti-PD-1/PD-L1 +/- CTLA-4 inhibitors and occurring also in pts with high PD-L1 expression, whereas it can be prevented by combining ICI with other non-ICI treatments.

9033 Background: In advanced NSCLC (aNSCLC) with PD-L1 < 50% chemo-immunotherapy is the standard of care. Although the activity of single agent pembrolizumab was reported, no biomarkers have been identified able to select patients who mostly benefit. The trial aimed to identify immune biomarkers associated with PFS in aNSCLC patients with PD-L1 levels < 50% treated with first-line pembrolizumab. Here we reported for the first time the clinical outcomes of the trial and circulating immune profiling (CIP) biomarkers correlated to PFS. Methods: This phase II trial was conducted at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. Eligible patients were previously untreated stage IIIB-IV NSCLC, EGFR and ALK wild type with PD-L1 < 50%, PS 0-2. PD-L1 was assessed with 22-C3 antibody (Dako). Patients received pembrolizumab 200 mg every 3 weeks until 35 cycles, disease progression or unacceptable toxicity. The primary endpoint was the association of immune biomarkers with PFS. OS, ORR, DCR, DoR and safety were secondary endpoints. CIP was performed by determination of absolute cell counts for 36 innate and adaptive immunity subsets through multiparametric flow cytometry on freshly isolated whole blood samples at baseline. An orthoblique principal components-based clustering approach and multivariable Cox regression model adjusted for clinical variables were used to analyse CIP variables and their correlation with clinical endpoints. Results: From May 2018 to October 2020, of 87 screened, 65 patients were enrolled. The median age was 70.9 years, most patients were male (67.7%), smoker (87.7%), non-squamous (83.1%), PDL1 + (70.8%). 12 patients (18.5%) had PS 2. During a median follow-up of 26.4 months (mo), 51 radiological progressions, 46 deaths and 60 PFS events were observed. The median PFS was 2.9 mo (95%CI 1.8 - 5.6) and the median OS was 12.1 mo (95%CI 8.7 - 17.1). The ORR was 24.1% (2 complete and 12 partial responses), DCR was 53.4% and median DoR was 14.5 mo (95%CI 6.4 - 24.9). Drug related G3-G4 adverse events were: 2 hyponatremia, 2 lipase increased, 1 pneumonitis. Out of 7 CIP clusters identified, 2 were statistically significant at multivariable analysis on 57 patients. Higher baseline counts of 8 subsets within these two clusters were associated with better PFS (HR values range: 0.88-0.98; p values range: 0.001- 0.016). The significant subsets included lymphocytes (cells expressing CD3, or CD19 or CD56, but lacking granulocyte and monocyte markers) and main NK subsets (including CD56dim CD16+, CD56dim CD16- and HLA-DR+ NK cells). Conclusions: This trial confirmed that pembrolizumab as first-line single agent is safe and active also in a subgroup of aNSCLC patients with PD-L1 < 50%. CIP biomarkers can be useful to identify patients with a favourable outcome, thus avoiding the adding toxicity of chemotherapy. Clinical trial information: NTC03447678.

TPS3636 Background: KRAS, NRAS, and BRAF mutations are well-established negative predictive biomarkers of response to anti-EGFR monoclonal antibodies (MoAbs) in metastatic colorectal cancer (mCRC) patients (pts). In clinical practice, RAS/BRAF wild-type (wt) patients receive first-line therapy regimens containing anti-EGFR agents. However, tumor heterogeneity might drive primary and acquired resistance to anti-EGFR MoAbs. In fact, circulating tumor DNA (ctDNA) testing reveals RAS/BRAF mutations in approximately 10% of pts who resulted in wt at tumor tissue. In addition, 30% to 50% RAS wt pts develop, during the treatment with anti-EGFR MoAbs, RAS mut can be detected in the ctDNA several weeks before clinical progression. As today, it is not known whether revealing RAS mut in liquid biopsy (LB) earlier than the appearance of a clinical/radiological disease progression, could impact pts’ outcomes. Similarly, there are no data suggesting the best therapeutic approach in patients with RAS/BRAF wt tissue and mutated ctDNA. Methods: This is a phase III, randomized, open-label, comparative, multicenter study to assess the superiority of Bevacizumab (BEV) compared to Cetuximab (CET) plus FOLFIRI in treatment naïve mCRC RAS/BRAF wt on tumor tissue (TT) and mutated in plasma samples. RAS/BRAF wt pts on TT will undergo the first LB, and RAS mut pts will be randomized 1:1 to receive FOLFIRI/CET (control arm) or FOLFIRI/BEV (experimental arm). Instead, RAS wt pts at first LB will be treated with FOLFIRI/CET up to 8 cycles. Pts who have not progressed after 8 cycles of treatment will undergo a second LB. If RAS mut was detected, pts will be randomized 1:1 to continue FOLFIRI/CET or switch to FOLFIRI/BEV. If not, pts will continue FOLFIRI/CET outside the clinical trial. Pts will be treated until disease progression, unacceptable toxicity, or withdrawal of consent. Among 26 pts screened at the first LB, actually 1 KRAS mut and 1 BRAF mut pts were detected. The primary endpoint is the PFS Plasma samples will be analyzed for KRAS, NRAS, and BRAF mutations by Idylla ctKRAS and Idylla ctNRAS-BRAF-EGFGR. All samples will be also analyzed by NGS, in order to better evaluate the correlation of tumor heterogeneity with pts’ outcomes. Clinical trial information: EudraCT Number: 2020-005078-82, NCT04776655.

9051 Background: Chemo-immunotherapy is the standard of care for patients with advanced NSCLC and PD-L1 < 50%. Efficacy has been reported in this setting with single agent pembrolizumab, but no reliable biomarkers yet exist for selecting patients likely to respond to single agent immunotherapy. The aim of this trial was to identify potential new immune biomarkers associated with PFS in NSCLC patients with PD-L1 < 50% treated with first line pembrolizumab. Methods: Advanced EGFR and ALK wild type treatment-naïve NSCLC patients with PD-L1 < 50% were enrolled. Gene expression profile was performed using nCounter PanCancer IO 360 Panel (Nanostring) on baseline tissue. Circulating immune profiling was performed by determination of absolute cell counts with multiparametric flow cytometry on freshly isolated whole blood samples at baseline and at first radiological evaluation. Gut bacterial taxonomic abundance was obtained by shotgun metagenomic sequencing of stool sample at baseline. Pembrolizumab was administered at 200 mg flat dose every 3 weeks until 35 cycles, disease progression or unacceptable toxicity. Omics data was analyzed with sequential univariate Cox Proportional Hazards regression predicting PFS, with Benjamini-Hochberg multiple comparisons correction. Biological features significant with univariate analysis were analyzed with multivariate Least Absolute Shrinkage and Selection Operator (LASSO). Results: From May 2018 to October 2020 65 patients were enrolled. Main characteristics were: male 67.6%, smokers 87.7%, PD-L1 positive 70.8%. Median follow up and PFS were 26.4 and 2.9 months, respectively. Gene expression profile was performed in 48 patients, microbiome in 54 patients and circulating immune profiling in 56 patients at baseline and in 46 patients at first radiologic evaluation. LASSO multivariate analysis with optimal lambda of 0.28 showed high expression levels of IRF9 and COMP genes was associated with an unfavorable PFS (HR 3.03, 1.52 – 6.02, p = 0.08 and HR 1.22, 1.08 – 1.37, corrected p = 0.06, respectively). High expression levels of CD244 (HR 0.74, 0.62- 0.67, p = 0.05), PTPRC (HR 0.55, 0.38 – 0.81, p = 0.098), KLRB1 (HR 0.76, 0.66 – 0.89, p = 0.05) in tissue samples and NK cells/CD56dimCD16+ (HR 0.56, 0.41 – 0.76, p = 0.006) in peripheral blood at baseline and non classical CD14dim CD16+ monocytes (HR 0.52, 0.36 – 0.75, p = 0.004), eosinophils (CD 15+CD16-) (HR 0.62, 0.44 – 0.89, p = 0.003) lymphocytes (HR 0.28, 0.15 – 0.5, p < 0.001) in peripheral blood after first radiologic evaluation were associated to a favorable PFS. No microbiome features were selected by LASSO. Conclusions: To the best of our knowledge, this is the first prospective trial in NSCLC with PD-L1 < 50% performed with a multi-omic approach able to identify immune cell subsets and expression levels of genes associated to PFS under first line treatment with pembrolizumab. Clinical trial information: NTC03447678.

3506 Background: Despite advances in molecular segmentation of metastatic colorectal cancer (mCRC), beyond RAS status therapeutic actionability remains confined to the limited subgroups of ERBB2 amplified, BRAF mutated and MSI-H patients. Optimization of available treatments is therefore warranted. Rechallenge with anti-EGFR monoclonal antibodies is often empirically used with some benefit as late-line therapy. We previously found that mutant RAS and EGFR ectodomain clones, which emerge in blood during EGFR blockade, decline upon antibody withdrawal leading to regain drug sensitivity. Based on this rationale, we designed CHRONOS, a multicenter phase II trial of anti-EGFR therapy rechallenge guided by monitoring of the mutational status of RAS, BRAF and EGFR in circulating tumor DNA (ctDNA). To our knowledge, this is the first interventional clinical trial of liquid biopsy for driving anti-EGFR rechallenge therapy in mCRC. Methods: Eligible patients were PS ECOG 0-2 RAS/BRAF WT mCRC having first achieved an objective response and then progression in any treatment line with an anti-EGFR antibody containing regimen, displaying RAS, BRAF and EGFR ectodomain WT status in ctDNA at molecular screening after progression to the last anti-EGFR-free regimen. Clonal evolution in ctDNA was analyzed by ddPCR and next generation sequencing. Panitumumab 6 mg/kg was administered IV every two weeks until progression. The primary endpoint was objective response rate (ORR) by RECIST version 1.1 with independent central review. 27 total patients and 6 responses were required to declare the study positive (power = 85%, type I error = 0.05). Results: Between Aug 19, 2019 and Nov 6, 2020 52 patients were screened by liquid biopsy and 36 (69%) were negative in ctDNA for RAS/BRAF/EGFR mutations. Of these, 27 patients were enrolled in 4 centers. Median age was 64 years (range: 42-80). PS ECOG was 0/50%, 1/46%, 2/4%. Previous anti-EGFR was administered in 1st line in 63%, 2nd in 15% and > 2nd in 22%. Median number of previous treatments was 3. The primary endpoint was met, with 8/27 partial responses (PR) observed (2 unconfirmed) (ORR = 30%, 95% CI: 12-47%). Stable disease (SD) was obtained in 11/27 (40%, 95% CI: 24-59%), lasting > 4 months in 8/11. Disease control rate (PR plus SD > 4 months) was therefore obtained in 16/27 (59%, 95% CI: 41-78%). Median progression-free survival was 16 weeks. Median duration of response was 17 weeks (1 ongoing). Maximal grade toxicity was G3, limited to dermatological and occurring in 19% of patients. ctDNA dynamics were studied in all patients. Conclusions: Liquid biopsy-driven rechallenge with anti-EGFR antibodies leads to further objective responses in one third of patients. Genotyping tumor DNA in the blood to direct therapy can be effectively incorporated in the management of advanced CRCs. Clinical trial information: 2016-002597-12.

LBA111 Background: Early reports on cancer patients infected with COVID-19 have suggested a high mortality rate compared to the general population. Patients with thoracic malignancies are considered high risk given their age, preexisting comorbidities, smoking, and pre-existing lung damage in addition to therapies administered to treat their illness. Method: We launched a global consortium to collect data on patients with thoracic malignancies diagnosed with COVID-19 infection to understand the impact on this patient population. Goals of this consortium are to provide data for guidance to oncology professionals on treating patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus. Results: As of April 23, 2020, a total of 295 patients across 59 centers and 9 countries have been entered; median age 68, 31% female, 79% current/former smokers, HTN and COPD most common comorbidities; 73% NSCLC, 14% SCLC, 4% meso and thymic, 49% patients with stage IV disease, majority on chemo or chemo-IO and 24% receiving RT. The use of IO or chemo-IO does not appear to impact risk of hospitalization, while treatment with TKI appears to be associated with a decreased risk of hospitalization. 73% patients required hospitalization, most common therapy given to treat COVID was antibiotics 67%, antivirals 33%, and steroids 30%. Conclusion: With an ongoing global pandemic of COVID-19 our data suggest that patients with thoracic malignancies are at high risk for hospitalization. Updated results to be presented will include impact on specific chemo-IO regimens and number of lines of therapy, which may impact hospitalization and risk of death as well as which therapies administered may impact survival in patients treated for COVID-19.

TPS4124 Background: Moving stage III Colon Cancer (CC) into the precision medicine space is a priority in view of the lack of molecular markers driving adjuvant treatment. Retrospective studies have demonstrated the tremendous prognostic impact of circulating tumor DNA (ctDNA) analysis after curative intent surgery, and suggested that lack of conversion of ctDNA from detectable to undetectable after adjuvant chemotherapy reflects treatment failure. With these premises, we have designed the PEGASUS trial (NCT04259944). Methods: PEGASUS is a prospective multicentric study designed to prove the feasibility of using liquid biopsy (LB) to guide the post-surgical and post-adjuvant clinical management in 140 microsatellite stable Stage-III and T4N0 Stage-II CC patients. The LUNAR1 test (Guardant Health, Redwood City, CA, USA) will be used for ctDNA determination. For the efficacy analysis, the PEGASUS cohort will be compared with a 3:1 matched cohort of 420 patients from the TOSCA trial (NCT00646607). A LB executed 2-4 weeks post-surgery will guide a “Molecular Adjuvant” treatment: i) ctDNA+ patients will receive CAPOX for 3 months and ii) ctDNA- patients will receive capecitabine (CAPE) for 6 months but will be retested after 1 cycle, and if found ctDNA+ will be switched to CAPOX treatment. At the end of the “Molecular Adjuvant” treatment a further LB will be performed and instruct subsequent treatment. Positive patients (ctDNA+/+ and ctDNA-/+) will receive an up-scaled “Molecular Metastatic” systemic treatment for 6 months or until radiological progression or toxicity: i) ctDNA+/+ patients will be treated with FOLFIRI; ii) ctDNA-/+ patients with CAPOX. These patients will be subjected to a LB after 3 months and at the end of treatment: in case of positivity will be switched to FOLFIRI. ctDNA+/- patientswill receive a de-escalated treatment with CAPE for 3 months. 3 LB will be performed within 3 months and in case of positivity the patient will be switched to FOLFIRI. Patients with ctDNA-/- will be subjected to an interventional follow-up comprising 2 further LB and in case of positivity they will be switched to CAPOX treatment. PEGASUS is piggybacked to AlfaOmega (NCT04120935), a Master Observational Protocol that will follow patients from diagnosis to 5 years or recurrence/death (whichever comes first), collecting clinical data, radio-images and biological samples. AlfaOmega provides a clinical and logistic ecosystem for the seamless integration of PEGASUS clinical results with the biological underpinning of colon cancer. Clinical trial information: NCT04259944 .

e18084 Background: The use of PARP inhibitors (Olaparib-Niraparib) has shown an important benefit in PFS in patients with relapsed ovarian cancer both with gBRCA and non-BRCA mutation. Methods: This was a single-institution, retrospective cohort study of 93 patients. Clinical data were obtained by the review of the electronic medical report. The 93 patients were treated with PARP Inhibitors(PARP-I) between Apr 2014 and Dic 2019. The patients were evaluated according to age, BRCA mutation, pretreatment with Trabectedin, Bevacizumab, last line of pretreatment with Platinum-Gemcitabine+Paclitaxel versus Caelyx-Oxaliplatin, number of previous lines of chemotherapy, residual disease before PARP-I. Statistical analysis of survival was performed with Kaplan-Meyer, univariate and multivariate analysis with Cox regression. Disease Free Survival (DFS) was evaluated from the start of PARP-I therapy while Overall Survival (OS) from the diagnosis. Results: Median age was 64 (42-90), patients with germinal mutation BRCA were 34 (36.6%), 58 without mutation and 1 patient without genetical analysis. 20 (21,5%) patients were pretreated with Trabectedin plus Pegylated Liposomal Doxorubicine (PLD), while 8 (8,6%) with Trabectedin-Bevacizumab, 26 (28%) patients were pretreated with Bevacizumab +/- Trabectedin. Before PARP-I patients more frequently were pretreated with 2-3 line 60, 64.5%): in the last line of pretreatment chemotherapy 47 (50,4%) patients received PLD+-Oxaliplatin versus Carboplatin-Taxol or Carboplatin-Gemcitabine. In 64% of the patients CTscan or ecography showed residual disease > 1 cm before starting PARP-I treatment . Median follow-up was 17 months: 54 (58.1%) patients in PARP-I treatment relapsed, while 32 (34.1%) patients died. Multivariate analysis showed a significant association in the number of lines pretreatment: in more than 3 lines HR was 2.00 (CI 1.2-3.4, p = 0.012), according to residuum less or more 1 cm prior to start PARP therapy (logrank p = 0,0286). Conclusions: The administration of PARP is important for OS immediately after 2° line chemotherapy in platinum sensitive patients Logrank p = 0.0065, with higher response not significant, about OS specially if following non-anemic PLD-Oxaliplatin therapy (p = 0,0849 Logrank) Also significant is OS according to residuum less or more 1 cm prior to start PARP therapy (logrank p = 0,0286) The doses and relative reductions in PARP-I did not change efficacy.

4004 Background: In overall population, IDEA pooled analysis did not demonstrate non-inferiority (NI) regarding 3y DFS in pts with stage III CC receiving 3m vs. 6m of adj FOLFOX/CAPOX. However, in pts treated with CAPOX (especially in low-risk pts), 3m of therapy was as effective as 6m. Results of OS and 5y DFS are reported. Methods: OS was defined as time from enrollment to death due to all causes. OS NI margin was conservatively set to be Hazard Ratio (HR) = 1.11, which is equivalent to: the maximum acceptable loss of OS efficacy, by shortening treatment to 3m, was half of the OS efficacy gained in MOSAIC trial (i.e., 2.26% absolute reduction in 5y OS rate). Pre-planned sub-group analyses included by regimen and risk group for both OS and 5y DFS. NI was to be declared if the one-sided false discovery rate adjusted (FDRa) NI p-value < 0.025. Results: With an overall median survival follow-up of 72 m (range per study, 62 to 84 m), 2584 deaths and 3777 DFS events among 12,835 pts from six trials were observed. Across 6 studies, 39.5% of pts received CAPOX (rate by study, 0% to 75.1%). Overall, the 5y OS rate was 82.4% (3m) and 82.8% (6m), with estimated OS HR of 1.02 (95% confidence interval [CI], 0.95-1.11; FDRa NI p, 0.058) and absolute 5-y OS rate difference of -0.4% (95% CI, -2.1 to 1.3%). Overall, the 5y DFS rate was 69.1% (3m) and 70.8% (6m), with estimated DFS HR of 1.08 (95%CI, 1.01-1.15, FDRa NI p, 0.22). HRs (95% CI) within subgroups see table. Conclusions: 5y OS rate reported in IDEA trials was higher than historical rates, regardless of duration of therapy. While overall survival in IDEA did not meet prior statistical assumptions for NI in overall population, the 0.4% difference in 5y OS should be placed in clinical context. OS and 5y DFS results continue to support the use of 3m adjuvant CAPOX for the vast majority of stage III colon cancer pts. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies and cost associated with shorter treatment duration. Clinical trial information: NCT01150045; 2009-010384-16; NCT00749450; ISRCTN59757862; 2007-003957-10; UMIN000008543; 2007-000354 . [Table: see text]

7548 Background: Progression of disease within two years from start of therapy (POD24) is linked with poor outcome in follicular lymphoma. It is less clear whether POD24 affects overall survival (OS) also in extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma). Methods: We analyzed the dataset of the IELSG19 clinical trial (training set) to determine whether POD24 is associated with inferior OS. The study population included 401 EMZL patients (131 randomly assigned to chlorambucil treatment, 138 to rituximab and 132 to chlorambucil plus rituximab). Reproducibility was analyzed in an independent cohort (validation set) of 218 patients who received systemic treatment (chemotherapy, immunotherapy or both). In both, training and validation sets, we excluded from the analysis the patients who, within 24 months from treatment start, died without progression or were lost to follow-up without progression. Overall survival (OS) was calculated from disease progression in patients with POD24 and from 24 months after start of treatment in those without POD24 (reference group). Results: POD24 was observed in 69 of 401 patients of the IELSG19 study and 58 of 218 patients in the validation cohort. In the training set, the 10-year OS rates were 64% in the POD24 group and 85% in the reference group (HR = 2.42, 95%CI, 1.35-4.34; log-rank P = 0.002) and POD24 predicted poor outcome regardless of treatment type (multivariable Cox model, P = 0.003). The prognostic impact of POD24 was confirmed in the validation set, with 10-year OS rates of 48% in the POD24 group and 71% in the reference group (HR = 2.17, 95%CI, 1.20-3.93; log-rank P = 0.009). Conclusions: In patients with EMZL who received front-line systemic treatment, POD24 is associated with poorer survival and may represent a useful endpoint in future prospective clinical trial.

3501 Background: 6m of oxaliplatin-based treatment is an option as adj chemotherapy for patients with high risk stage II CC (T4, inadequate nodal harvest, poorly differentiated, obstruction, perforation or vascular/perineural invasion). The IDEA collaboration showed shorter treatment duration to be appropriate for most pts with stage III colon cancer. The results of the 4 IDEA studies with stage II pts are presented here. Methods: A prospective, pre-planned pooled analysis of high-risk stage II patients from 4 concurrently conducted randomized phase III trials (SCOT, TOSCA, ACHIEVE-2, HORG) was performed to evaluate non-inferiority (NI) of 3m compared with 6m (ref) of adj FOLFOX/CAPOX (regimen preselected, not randomized). The primary endpoint was disease-free survival (DFS), NI was to be declared if the 2-sided 80% confidence interval (CI) for DFS hazard ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.2. 542 DFS events were required to provide 80% power to declare NI. NI was also examined within regimen, T4 (Yes v No) and inadequate nodal harvest (Yes v No) as pre-planned subgroups. Results: The primary analysis included 3273 randomised pts of which 1254 had FOLFOX and 2019 had CAPOX. There were 552 events and the median follow-up was 60.2 m. There was significantly less grade 3-5 toxicity with 3m treatment (p < .0001). The 5-year DFS rate was 80.7% and 84.0% for 3m and 6m treatment with an estimated DFS HR of 1.18 (80% CI:1.05-1.31, p for NI = 0.404). For CAPOX the estimated HR was 1.02 (80% CI: 0.88-1.17, p for NI = 0.087) and for FOLFOX the estimated HR was 1.42 (80% CI: 1.19-1.70, p for NI = 0.894). The test for interaction between duration and regimen was not statistically significant (p = .174 adjusted for multiple testing) but was stronger than that for the other subgroups examined. Conclusions: In the overall population non-inferiority for 3m adj treatment in pts with high-risk stage II CC was not shown. As with the stage III population the choice of adj regimen appears important (although this did not reach statistical significance) with a small difference in DFS between 3 and 6 m treatment if CAPOX is used. Clinical trial information: ISRCTN59757862.

Purpose Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. Methods MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU + levamisole or FU + leucovorin; n = 229) versus no postsurgical treatment (n = 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Results Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P = .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; 95% CI, 0.42 to 2.91; P = .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n = 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; 95% CI, 1.02 to 8.54; P = .04). Conclusion Patient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making.

3599Background: The IDEA collaboration pooled data from nearly13,000 patients (pts), comparing 3 vs. 6 months (m) of adjuvant fluoropyrimidine plus oxaliplatin to test noninferiority for disease-fr...

3594Background: HER2 amplification (HER2+) in metastatic colorectal cancer (mCRC) is associated with resistance to anti-EGFR antibodies and response to HER2 targeted therapies. This study assessed ...

e13076Background: mCHT is the minimum biologically effective dose of a CHT agent, given at regular dosing regimen with no prolonged drug free interval. Aim of this observational retrospective study...

e21101Background: Several studies have proven the efficacy of maintenance chemotherapy (CT) in advanced NSCLC. The use of low dose (i.e. metronomic) anti-mitotic drugs could exert an anti-angiogeni...

581 Background: We have reported with the HERACLES Trial that HER2 amplification is a clinically relevant genetic alteration in metastatic colorectal cancer (mCRC). With present study, we aim to develop and internally validate a new diagnostic model for HER2 status in patients with mCRC based on clinicopathological characteristics to improve selection for HER2-targeted therapies and to refine negative selection for EGFR-targeted agents. Methods: Patients with KRAS exon 2 WT mCRC underwent molecular screening of HER2 according to HERACLES criteria (immunohistochemistry 3+ or 2+ in equal or more than 50% of cells, confirmed by FISH) for enrollment in HERACLES clinical trials with HER2-targeted therapies. All HER2-positive cases and a fraction of negative consecutive cases were annotated with clinical and pathological variables. A multivariable logistic regression model with a linear combination of all clinical and pathological characteristics as predictors was fitted to the complete set of data. A regression modeling strategy was applied to the full model to identify predictors explaining the bulk of HER2 amplification. Results: From August 2012 to June 2017, a total of 80 HER2-positive mCRC cases were detected out of 1355 screened patients. The large majority of HER2-positive primary tumors appeared to be left colon- or rectal-sided (88.0%). None of the relevant clinicopathological features explained the bulk of HER2 amplification, even though trends were observed for sidedness (left colon and rectal > proximal, OR 1.75, 95% CI 0.76-4.16), tumour grading (high > low, OR 2.21, 95% CI 0.19-26.38), and metastatic burden (high > low, OR 1.29, 95% IC 0.94-1.77). In a secondary analysis, patients with HER2-amplified mCRC who received treatment with anti-EGFR agents (n = 64) showed poorer outcome (objective response rate: 30% vs 55%, p = 0.044 and progression-free survival: 5.8 months vs 7 months, p = 0.056). Conclusions: Testing for HER2 should be offered to all patients with mCRC since it is unlikely to predict the occurrence of this biomarker based on main clinicopathological features. Patients with HER2-amplified mCRC are less likely to respond to anti-EGFR therapy.

PURPOSE: To assess the activity, efficacy, and tolerability of single-agent paclitaxel and a platinum-containing regimen in previously treated patients with recurrent ovarian cancer. PATIENTS AND METHODS: Patients who achieved complete remission with platinum-based regimens and whose disease recurred after a progression-free interval of more than 12 months were included in the study. Every 21 days, patients received paclitaxel 175 mg/m2 intravenously (IV) over 3 hours or cyclophosphamide 500 mg/m2, doxorubicin 50 mg/m2, and cisplatin 50 mg/m2 (CAP) IV. RESULTS: Between June 1992 and May 1995, 97 consecutive patients with assessable or measurable disease were randomized to paclitaxel (n = 50) or CAP (n = 47). The median number of cycles on each arm was six. Toxicities included grade 3/4 leukopenia (4% for paclitaxel v 34% for CAP), grade 3/4 neutropenia (13% v 36%), grade 1/2 myalgia (19% v 4%), allergic reactions (15% v 2%), and grade 2/3 nausea and vomiting (17% v 51%). Complete responses were achieved in 17% and 30% of patients receiving paclitaxel and CAP, respectively, and partial responses were achieved in 28% and 25%, respectively (P = .062). At a median follow-up time of 49 months, median progression-free intervals were 9 months for paclitaxel and 15.7 months for CAP (Cox analysis: hazards ratio [HR], 0.60; 95% confidence interval [CI], 0.37 to 0.97; P = .038); median overall survival times were 25.8 months for paclitaxel and 34.7 months for CAP (Cox analysis: HR, 0.58; 95% CI, 0.34 to 0.98; P = .043). CONCLUSION: Rechallenge with either single-agent paclitaxel or platinum-based chemotherapy is effective in this patient population. Preliminary results suggest that single-agent paclitaxel may not be as active as platinum-based chemotherapy in recurrent ovarian cancer. Larger randomized trials are needed.

LBA1 Background: Since 2004, 6 months (m) of oxaliplatin (oxali)-based treatment has been the standard of care as adjuvant therapy for stage III CC. Since oxali is associated with cumulative neurotoxicity, shorter duration of adjuv therapy could spare pts toxicity and lead to substantial saving in health expenditures. Methods: A prospective, pre-planned pooled analysis of 6 concurrently conducted randomized phase III trials (SCOT, TOSCA, Alliance/SWOG 80702, IDEA France (GERCOR/PRODIGE), ACHIEVE, HORG) was performed to evaluate the non-inferiority (NI) of 3m compared with 6m (ref) of adjuv FOLFOX/XELOX. The primary endpoint was disease-free survival (DFS), defined as time from enrolment to relapse, 2nd CRC, and death (all causes). NI was to be declared if the 2-sided 95% confidence interval (CI) for DFS hazard ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.12. NI was examined within regimen and stage subgroups as pre-planned. Results: The analysis included 12,834 pts from 12 countries, accrued from 6/07 to 12/15. Stage distribution: 13% T1-2, 66% T3, 21% T4; 28% N2; 40% received XELOX. G3+ neurotoxicity was higher in the 6m v 3m arm (16 v 3% FOLFOX, 9 v 3% XELOX, p

e15029Background: Bevacizumab improves progression-free survival (PFS) and overall survival (OS) of metastastic colorectal cancer (mCRC) patients when added to doublets in first-line setting. In th...

705 Background: Bevacizumab (BEV) improves progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) patients (pts) when added to doublets in first-line setting. Yet, its use in unfit and older mCRC pts remains controversial. This systematic review and pooled-analysis evaluated the efficacy and safety data of BEV combined with first-line fluoropyrimidine monochemotherapy in unfit or elderly mCRC pts. Methods: A literature search to identify studies using first-line fluoropyrimidine monochemotherapy plus BEV in unfit pts was performed in PubMed and EMBASE databases up to May 2015. Unfit pts were selected based on age, comorbities and health status, along with monochemotherapy as the only therapeutic option. The random-effects model was used to combine the effect estimates and the I2 index to quantify the between-study heterogeneity unexplained by sampling error. Results: We screened 1,304 papers and, after a double check, 56 were considered for full text evaluation: 38 were excluded and 10 were deemed not evaluable for lack of data on unfit pts, whereas 8 (3 RCTs, 4 single arm phase II trials and 1 prospective cohort study), including 782 pts, were considered eligible for the meta-analysis. Administered monochemotherapy was capecitabine in 531 (67.9%) pts and 5-fluorouracil (5-FU) in 251 (32.1%); 500 (63.9%) pts also received BEV. Median age was 75 years, 441 (56.4%) pts were male, ECOG performance status was 0-1 in 684 (87.7%) pts. The combination with BEV produced advantages in terms of both OS (HR 0.79; 95% CI: 0.64-0.98, P = 0.03; I2= 0%) and PFS (HR 0.52; 95% CI: 0.43-0.64, P < 0.00001; I2= 0%; pooled effect estimates of RCTs have been previously reported). As expected, higher rates of all grade hypertension (27% vs 4.9%), bleeding (24% vs 6.4%), thromboembolic events (10% vs 5%) and proteinuria (25.6% vs 8.2%) were observed in the BEV combination. Conclusions: Adding BEV to first-line fluoropyrimidine monochemotherapy, either capecitabine or 5-FU, significantly improved PFS and OS in unfit and elderly pts with mCRC, with a manageable safety profile and no unexpected side effects.

8048 Background: While the benefit of EGFR tyrosine kinase inhibitors in EGFR mutated NSCLC patients (pts) is undisputed, their usefulness in wtEGFR pts is still questioned. The TAILOR, DELTA and P...

3508 Background: We conducted a phase II of trastuzumab (T) and lapatinib (L) in HER2-amplified, KRAS exon 2 wild-type, mCRC pts resistant to standard therapies (HERACLES Trial EudraCT 2012-002128-...

e11591 Background: Few reports in the literature give detailed figures on metastatic patterns in HER2+ MBC. This study reports a detailed analysis of MBC patients (pts) presentation, the developmen...

e11565 Background: Trastuzumab has dramatically improved the prognosis of patients with HER2+ BC. This study reports the practice patterns across different treatment lines and the major clinical outcome of MBC patients receiving T. Methods: We analyzed an institutional database containing the treatment history patients who received at least one trastuzumab-based regimen for HER2+ MBC. Time to progression (TTP) was evaluated for each line of therapy; a Cox regression model with treatment line as continuous predictor was evaluated, and a linear and a quadratic term were introduced in the model. Results: A total of 112 patients were analyzed. Median patient age was 50 (range 26 – 74) years, 16% were metastatic at debut, 71% presented with hormone receptor positive disease, 58% had soft tissue metastases (met), 49.5% visceral met, 42% bone met and 4.5% brain met. The median number of lines of treatment was 6 (range 1-17). A combination of chemo- and/or targeted-therapy was the most frequently used regimen acr...

e14611 Background: Retrospective studies showed that efficacy of C increases in molecularly-defined subsets of KRAS wt mCRC pts. In pretreated pts, biweekly C seems as effective as a weekly schedule. Aim of this field-practice study was to evaluate the efficacy of FOLFIRI plus biweekly C (C-FOLFIRI) as first-line treatment for mCRC and prospectively validate PTEN expression as a prognostic marker. Methods: Pts with previously untreated metastatic KRAS wt mCRC not suitable for curative-intent resection were eligible. Initially, pts were randomized to receive FOLFIRI alone or in combination with C (500 mg/m2 every two weeks). After a protocol amendment, pts were assigned to receive only C-FOLFIRI, while the FOLFIRI alone arm was discontinued. Clinical outcome was assessed according to expression of PTEN and MET by immunohistochemistry (IHC), as well as to BRAF mutations. Results: From April, 2009 to June, 2012, a total of 89 pts were enrolled. 35 pts were randomly assigned to receive FOLFIRI alone, while 54 pts received C-FOLFIRI: 33 were treated in the random phase and 21 after protocol amendment. Median overall survival (OS) was 17.7 months for FOLFIRI and 23.3 months for C-FOLFIRI. Corresponding median progression-free survival was 8.2 and 6.8 months, respectively. Objective response rate was 52.0% for FOLFIRI and 52.3% for C-FOLFIRI. The toxicity profile of C-FOLFIRI was consistent with that expected from a weekly C schedule. 23/38 pts (61.0%) assessed for PTEN were positive for IHC expression, 8/39 pts (21.0%) had a MET high status, 6/45 pts (13.3%) had BRAF mutations. In pts treated with C-FOLFIRI, only BRAF mutations negatively affected OS (Hazard ratio mutations vs. wt: 4.77; 95%CI 1.41-16.13; p = 0.01). Conclusions: Safety, effectiveness and generalizability of C-FOLFIRI validate in field practice results gained with FOLFIRI plus a weekly C schedule. Despite the small sample size, analysis of BRAF mutations reaffirms the strong prognostic impact of this biomarker. The extended analysis of BRAF mutations, PTEN and MET expression on all pts is ongoing. Data will be presented. Clinical trial information: NCT01068132.

LBA8005 Background: Second-line therapy for advanced NSCLC patients (pts) after progression on platinum-based regimens typically employs CT or E. Improved PFS in E-treated pts is associated with EGFR sensitizing mutations. However, a test for optimizing treatment in pts with wild-type or unknown EGFR mutation status or squamous histology is of clinical value. VeriStrat (VS) is a serum protein test that assigns "good" (VSG) or "poor" (VSP) classification and has demonstrated prognostic and predictive utility. PROSE is a multicenter prospective randomized biomarker validation trial, designed to evaluate the ability of VS to predict survival in second-line NSCLC pts treated with E or CT. It is the first completed prospective randomized biomarker validation trial following the MARVEL design (Freidlin et al. JNCI. 2010). Methods: 285 pts, stratified by ECOG-PS, smoking, and blinded pretreatment VS classification, were randomized 1:1 to receive E or CT at standard doses. Primary endpoint was overall survival (OS) and the primary hypothesis was significant interaction between VS status and treatment. Sample size was calculated based on an estimated 65%/35% VSG:VSP ratio and hazard ratio (HR) for interaction of 2.35, with a 2-sided α=0.05 and 90% power. Results: 285 pts were randomized and 263 (129 CT, 134 E) included in the per protocol primary analysis. 68% of pts in CT arm and 72% in E arm were classified as VSG. Analysis was performed at 226 events. The trial reached its primary objective of significant interaction between treatment and VeriStrat classification with an interaction p value of 0.037. Pts in the VSP group performed worse on E compared to CT (HR: 1.72, 95% CI: 1.08-2.74); there was no significant difference in OS between treatments in the VSG group (HR: 1.09, 95% CI:0.79-1.50). 194/198 pts with histologic diagnosis had tissue available for EGFR and KRAS mutations. Conclusions: The results suggest that VS status is predictive of differential OS benefit for E versus CT in second line setting, complementing the result from a retrospective analysis of NCIC BR.21 where the prognostic behavior of VS was established (Carbone et al. JTO. 2012). Clinical trial information: NCT00989690.

esting results achieved with dacomitinib (PF-00299804), a pan– human epidermal growth factor receptor (HER) inhibitor. The authors demonstrated that dacomitinib was able to selectively, irreversibly (covalently) bind to the adenosine triphosphate domain of each of the three kinase-active members of the HER family: epidermal growth factor receptor (EGFR)/HER1, HER2, and HER4. In addition, dacomitinib demonstrated significantly improved progression-free survival compared with erlotinib in the treatment of non–small-cell lung cancer, with acceptable toxicity. The authors concluded that the progression-free survival benefit was observed in most clinical and molecular subsets, notably KRAS wild-type/EGFR any status, KRAS wild-type/EGFR wild-type, and EGFR mutants. In this phase II trial, which was not powered for subgroup analysis, it is important to note that the significant imbalance (20.2% v 11.7%) in EGFR mutations in favor of dacomitinib may be principally responsible for the overall positive results. In fact, patients with EGFR mutations shift the risk of progression from a reduction of 34% to 30%, rendering the overall results not statistically significant. Similar results, also not statistically significant, are found if we consider only the subgroup of patients with wildtype EGFR mutations. However, an interesting benefit in wild-type EGFR mutations can be hypothesized, possibly driven by other biomarkers, such as the overexpression of HER2 or the activation of the phosphatidylinositol 3-kinase pathway. 2,3 We agree that dacomitinib is an interesting drug, but its development should not be in an unselected patient population. Today, a target agent must be used for a particular target to avoid another “me too” drug for unselected patients.

e19034 Background: Targeted therapy against the mutated form of BRAF V600 is a proven effective therapy for melanoma. Objective of this exploratory study was to describe the change over time of PET-scan results and verify the association of PET-scan examination with the objective response (OR) (defined by RECIST criteria) in melanoma pts treated with vemurafenib. These preliminary results reported here regards the description of changes over time of PET-scan. Methods: Patients treated with vemurafenib at our institution were considered eligible. Patients were evaluated with PET-scan at baseline and at day 7, 15 and 30 from the start of therapy. Maximal Standardized Uptake Value (SUVmax) and Total Lesion Glycolysis (mean SUV x lesion volume) were recorded and compared for single lesions in the 4 exams. Differences between each PET-scan performed during therapy and baseline were calculated and coded as yes/no response basing on predefined criteria. Association of PET responses and achievement of OR were estimated by means of logistic regression models. Odds ratio and C statistics were used to define strength of association and discriminant capability. C statistics obtained with PET/CT at different timepoints were compared. Results: As of January 2012, 7 out of 20 required pts have been enrolled. A total of 48 lesions were available for evaluation. A reduction in lesion SUVmax and TLG values compared to baseline was evident in all the post-therapy studies (reduction in SUV max at day 7 – 51 ± 28 %, day 14 – 67 ± 24 % and day 30 –69 ± 29 %, reduction in TLG at day 7 – 41 ± 83 %, day 14 – 69 ± 35 % and day 30 – 68 ± 37 %). A comparison of the day 15 and day 30 studies showed essentially stable uptake values (SUV max variation -3 ± 41 %, TLG 5 ± 56 %). However, 14/23 lesions in 3 patients showed increased SUV max and TLG values between the day 15 and day 30 studies likely indicating early signs of treatment resistance. Conclusions: Our preliminary results suggest that PET/CT may be an early surrogate marker of treatment response to vemurafenib. Sequential monitoring of targeted therapy with PET/CT may be useful in identification of treatment resistance, aid in tailoring alternative strategies and deserves further investigation.

TPS7109 Background: This is an ongoing phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy, based on thymidilate synthase (TS) and excision-repair cross-complementing -1 (ERCC1) gene expression versus standard adjuvant chemotherapy in completely resected stage II-IIIA non-small cell lung cancer (EudraCT #: 2008-001764-36). Methods: In all registered patients, before randomization, expression of ERCC1 and TS is assessed by qRT-PCR on paraffin-embedded tumor specimens in a central laboratory. Randomization is stratified by stage and smoking status. Trial was emended on Feb, 2011 with the 7th staging system. Primary end point is overall survival; secondary end points include recurrence-free survival, therapeutic compliance, toxicity profile and comparative evaluation of ERCC1 and TS mRNA versus protein. It is assumed that the 5-year survival in the control arm is 45% and the hazard reduction associated to the experimental treatment is 30%. With a power of 90% to detect the estimated effect with log-rank test, a significant level of 5% (2 tails), 336 events have to be observed; the expected total number of patients is 700. The final statistical analysis will group together all control arms and all tailored chemotherapies groups. Efficacy analysis will be done on an intent-to-treat basis. Cox proportional hazard model will be used for estimating hazard ratios after adjusting for relevant variables. Within 45 days post-surgery, patients in each genetic profile are randomized to receive either a standard chemotherapy selected by the investigator (cisplatin/vinorelbine, cisplatin/docetaxel or cisplatin/gemcitabine) or an experimental treatment (tailored arms) selected as follows: 1) high ERCC1 and high TS 4 cycles of single agent paclitaxel 2) high ERCC1 and low TS 4 cycles of single agent pemetrexed 3) low ERCC1 and high TS 4 cycles of cisplatin/gemcitabine 4) low ERCC1 and low TS) 4 cycles of cisplatin/pemetrexed. All chemotherapy regimens are administered for a total of 4 cycles on a 3-weekly basis. Currently, 312 patients have been randomized from 26 institutions mainly located in Italy and Germany (average enrolment: 13 patients/month).

7087 Background: This phase I study investigated the safety and efficacy of sorafenib in combination with cisplatin and pemetrexed in untreated MPM patients (pts). Methods: Pts with an histological...

9028 Background: The rate of neuropathic pain (NP) control with single agents is low. Oxycodone and pregabalin alone have proven activity in NP, but controlled data on their rational combination is...

7518 Background: Based on the results of the 2 INTACT trials, EORTC trial 08021 evaluated the role of G, an oral TKI inhibitor, administered following standard first-line chemotherapy (CT) in pts w...

e19093 Background: Patients with SCLC progressed after first-line chemotherapy (FL) have a poor prognosis and the evidence of a benefit of SL is still limited.This retrospective analysis evaluates the clinical outcomes of patients who received a SL treatment after failure of a FL for SCLC Methods: Retrospectively we reviewed 166 consecutive patients who failed a FL and received a second or third-line treatment, between 1993 and 2008 in 17 institutions. We divided patients for analysis in four subgroups, according to the type of SL administered: 1) Platinum-based (P) rechallenge 2) Non-platinum-based polichemotherapy 3) Non-topotecan monochemotherapy 4) topotecan monochemotherapy. Our endpoints were Overall survival (OS), Progression free survival (PFS) and Response Rate. Survival curves were designed with Kaplan-Meier method and Cox proportional hazard model was used for investigating factors which influence survival Results: Median age was 63 (range 25–86). Median OS from the SL was 6.2 months and PFS 2.9. 163 patients received a platinum based chemotherapy as FL, among them 67% obtained a response (CR=14%, PR=53.7%) and 19% had a progressive disease. 74% of patients had a PS 0–1 when started on SL. Moreover, 50 patients underwent also a third-line chemotherapy. Of the 23 CR at FL, 7 patients achieved a response in SL(30%), of the 85 PR only 19 (22%) and of the PD+SD only 6 (16%) (test for trend p=.03). No statistical differences among regimens groups were found; however, patients rechallenged with P went better then others when a long PFS in FL was demonstrated (p=.02) Conclusions: The clinical benefit of SL therapy for SCLC is poor and strictly dependent on response and on duration of response with FL treatment. Our retrospective analysis confirms that median OS for patients receiving SL is about 6 months and median PFS 2.9 months. A rechallenge with platinum should be the best options in patients with a long PFS in FL. Single agent topotecan, the most investigated agent in the literature, did not show evidence of superiority against other chemotherapy regimens No significant financial relationships to disclose.

e20693 Background: The waiting room is one of the most emotional place in oncological divisions; indeed, it's presumed that the waiting moment makes increase thoughts most related to the experience of disease and its treatment, making them sometimes unbearable. At present, any evaluation of the emotional states in the waiting room doesn't exist, therefore we analyzed the most prevailing emotions and feelings for patients in this context. The identification of them should address also ways to improve patients well being in these moments. Primary objective was to prospectively evaluate the prevailing emotional state patients and feelings in oncological waiting rooms; secondary endpoint is to develop a questionnaire to be further validated and useful to quantify how changes in the environment, as people and furnishings, could reduce prevailing emotional intensity. Methods: A committee of psychoncologists, oncologists, psychiatrists, volunteers, nurses, past patients, and statisticians identified the emotional states considered most important (relationship with environment, surrounding people and treatment, recurrent thoughts about disease and life, fears and things that could ease the wait and prevailing emotions) and developed a questionnaire. In May 2008 for two consecutive weeks this questionnaire was administered by the same dedicated nurse to all the outpatients afferred to our Oncology Department. The compilation of questionnaire was spontaneous and anonymous and it collected also age, sex, whether the patient was under treatment or in follow up and whether was accompanied. Results: In two consecutive weeks 300 questionnaires have been collected in the waiting rooms. Statistical analysis showed that the most prevailing emotions are sadness (51%), fear (29%), anger (17%) and joy (7%). A positive disposition (Cronbach alpha 0.60) and anxiety (Cronbach alpha 0.64) were also assessed. No differences in answers were revealed among patients waiting for follow up and patients waiting for chemotherapy and among different ages. Conclusions: The level of negative feelings seems higher than in other conditions and suggests that active intervention to improve the waiting in waiting rooms is warranted. A further validated questionnaire is ongoing also to evaluate emotions intensity. No significant financial relationships to disclose.

4008 Background: Patients (pts) with CC demonstrating high-frequency MSI (MSI-H) have a stage-independent improved survival compared to pts with microsatellite- stable (MSS) tumors. We have previously published that MSI status is a predictive marker for lack of response to 5-FU-based chemotherapy (rx) (Ribic, NEJM 2003). dMMR by immunohistochemisty for MMR proteins is an almost perfect predictor for MSI status. We sought to confirm the value of dMMR as a predictor of survival benefit from adjuvant rx in stage II & III CC pts in an independent dataset drawn from randomized clinical trials. Methods: MSI or IHC analyses were performed on tumors from pts enrolled in trials conducted by the NCCTG (N=135), GIVIO (N=183), and ECOG (N=23) that have not been used in previous MSI or dMMR analyses. All trials randomized pts with stage II and III CC to either 5-FU based rx (either 5-FU + levamisole or 5-FU + leucovorin, n=166)) or no post-surgical rx (n=175). XX microsatellite loci from the National Cancer Institute ...

14662 Background: The survival benefit of TKIs in advanced non small lung cancer (NSCLC) is modest and gefitinib and erlotinib are usually considered drugs with similar efficacy. Methods: We perfor...

11594 Background: Male breast cancer is an uncommon disease, 1%(0.7 %) of all breast cancer. Its aetiology, clinical behaviour and treatment are not well-known. The objective of our report was to analyze the form of presentation and the clinical evolution of patients with male breast cancer studied from 1987 to 2006. Methods: A total of 142 men with a diagnosis of breast carcinoma were registered and treated at the cancer-based hospitals linked to ORION collaborative group. 138 men had nonmetastatic breast carcinoma at diagnosis and were included in this analysis. Patients’ charts were retrospectively reviewed to obtain details of patient characteristics, adjuvant therapy, and outcomes. Analysis was performed with descriptive statistics; the log-rank test was used to compare outcomes. Results: The median patient age was 61.9 years (range, 38–84 yrs). Positivity for family cancer history: 16 out of 123 cases, 3 were unknown. Pathological characteristics included: pT1 tumors 22 pts (15.5%); pT2a 33 (23%), p...

7508 Background: This phase III study tested the hypothesis whether 3 preoperative cycles of gemcitabine-cisplatin followed by radical surgery provides a reduction in the risk of progression compared with surgery alone in patients (pts) with stage IB- IIIA NSCLC. Methods: Chemotherapy naive pts with clinical stage T2N0, T1–2N1, or T3N0–1 received either preoperatively cisplatin (75 mg/m2, day 1) and gemcitabine (1,250 mg/m2, days 1&8), q3week followed by surgery (C+S) or surgery alone (S). In 2004 the enrollment was closed early after the inclusion of 270 out of 700 planned pts because investigators felt it unethical to complete the study treating patients with surgery alone due to positive adjuvant studies. Results: From September 2000 to December 2004, 141 pts were randomized to S and 129 to C+S. Median age was 63/61 years, and most of pts were male (89%/78%). Stage IB/IIA disease was reported in 55% and 46%, respectively. The commonest histology was squamous cell carcinoma (45%/37%) followed by adenoca...

20502 Background: The incidence of venous thromboembolism (VTE), as well as its prognostic role among advanced colorectal cancer (ACC) patients are still not completely understood. Methods: This su...

14596 Background: FOLFOX is usually employed as first line treatment of MCC. Some patients (pts), for both clinical reasons and poor compliance, are not eligible for CVD insertion. At the moment, it is not clear if FUFOX (with 5-FU bolus) is less active than FOLFOX (with 5-FU infusion). We evaluated the outcome of MCC pts treated, as first line, with FUFOX. Primary end-point is efficacy. Secondary endpoints are time to progression (TTP) and overall survival (OS). Toxicity is also reported. Materials and Methods: We analysed all consecutive MCC patients who referred to our centre, without CVD, treated with the Hochster regimen: Oxaliplatin 85 mg/m2 days 1, 15; Leucovorin 20 mg/m2 and 5-FU 500 mg/m2 bolus days 1, 8, 15 - every 28 days. Response rate was evaluated with RECIST criteria. TTP and OS were analysed with Kaplan-Meier methods. Results: From July 2003 to October 2006 we treated 25 MCC pts. Main characteristics were: median age 71 years (range 46–79), 12 males, 13 females; PS 0–1; metastatic sites: liver 15 pts; lung 6; abdominal 10. 2 pts are early. A total of 128 courses were administered (5,4 median courses/pt, range 3–9). 5/23 pts (21.7% 90%CI: 9.0%-40.4%) had a PR and 2 achieved a secondary complete surgery. 15/23 pts (65.2%: 90%CI: 46.0%-81.4%) had a SD and 3 pts (13.0%: 90%CI: 3.7%- 30.4%) had a PD. At the moment of analysis 14 pts are still alive with a median follow up of 25 months; the median time to progression is 7.2 months. This combination was well tolerated with no grade 3–4 toxicities observed. G1-G2 peripheral neurotoxicity is reported in 15/25 pts (60%). Other common toxicities are: G1–2 haematological in 10 pts (40%); G1–2 gastrointestinal in 7 pts (28%); asthenia 5 pts (20%). Conclusions: We observed a low response rate, but high number of stable disease. Toxicity was acceptable. Although this is a not controlled study, this regimen seems to be less effective than infusional regimens but, due to the high control rate of disease (86.9%) we can consider it an alternative choice for patients that refuse or cannot receive continuous infusion. No significant financial relationships to disclose.

13562 Background: Until recently, 5-fluorouracil (5-FU) has been the mainstay of treatment for advanced CRC. In the last years, irinotecan and oxaliplatin have been shown to improve survival in combination with 5-FU. It is unclear if this improvement requires the use of these agents as first-line treatment or their sequential use during the course of disease. Methods: In order to assess the impact on prognosis of the first-line chemotherapy regimen, we retrospectively reviewed the outcome of all patients (pts) with advanced CRC treated at our insitution from May 1997 to December 2003. During this period our standard first-line chemotherapy moved from 5-FU and folinic acid (FA) to FOLFIRI to FOLFOX regimens. We analyzed changes in overall survival over time according to administered treatments. Results: From May 1997 to December 2003, 376 consecutive pts with advanced CRC were treated at our institution, 118 from 1997 to 1999, 135 from 2000 to 2001, 123 from 2002 to 2003. Patient characteristics did not vary over time for the 3 cohorts: median age was 62 years (range 26–83), 58% of pts were male, 72% had single metatastic site, liver was the main disease site (72%). In the first cohort (1997–99) the standard first-line treatment was 5-FU/FA, in the second (2000–01) FOLFIRI, and in the third (2002–03) FOLFOX. The number of pts who underwent 1, 2 o 3 lines of treatment for metastatic disease was similar for the 3 cohorts. The median overall survival was 21.4 months (95% CI 19.3–23.3). As shown below, no statistically significant differences were observed among the cohorts. Conclusions: Our retrospective analysis shows that the use of oxaliplatin and irinotecan has pushed the overall median survival to 21 months. The outcome of pts has been similar during the period 1997–2003 despite the shift in standard first-line treatment from 5-FU/FA to FOLFIRI to FOLFOX. These results are reasonably due to the sequential use of all the active regimens. [Table: see text] No significant financial relationships to disclose.

5068 Background: The role of systematic pelvic and para-aortic lymphadenectomy at SLS in ovarian cancer patients has not been addressed by randomized clinical trials (RCTs). We conducted a RCT to determine whether LY improves progression-free (PFS) and overall survival (OS) compared with SA. Methods: From January 1991 through December 1999, 303 eligible patients (i.e. patients with FIGO stage I-IV epithelial ovarian carcinoma at up front surgery and in complete remission after primary debulking surgery and first line chemotherapy) were randomly assigned to undergo LY (N = 156) or SA (N = 147) at the end of SLS. Survival was analyzed using a Cox multivariable regression analysis. All statistical tests were two-sided. Results: Median operating time was longer and the percentage of patients requiring blood transfusions was higher in the LY arm than the SA (240 vs 135 min., P < .001, and 30% vs 10%, P < .001, respectively). In the LY arm and SA arm the median number of removed nodes and the percentages of patients with nodal involvement was statistically different (44 vs 8, P < .0001, and 24% vs 13%, P = 0.018, respectively). At a median follow-up of 59 months, 156 events (i.e., recurrences or deaths) were observed, and 98 patients had died. The 5-year progression-free and overall survival was 41% and 65% for LY, 49% and 61% for SA, respectively. The risk for first event (hazard ratio [HR] = 1.11, 95% CI = 0.81 to 1.53; P = .50) and death (HR = 0.79, 95% CI = 0.53 to 1.18; P = .24) after adjustment for residual tumor at first surgery was not significantly different between the two arms. Conclusions: Although LY at SLS seemed to improve overall survival, this survival gain (21% decrease in the hazard of death) was not statistically significant and therefore the routine use of LY at SLS for ovarian cancer is not supported by this RCT. No significant financial relationships to disclose.

774 MOON study aimed at investigating presentation, treatment and evolution of BM in BC pts and comparing them to metastases (MTS) at different sites. Four-hundred and fifty-nine BC pts have been e...

Limburgs Univ Ctr, Diepenbeek, Belgium. Stanford Univ, Med Ctr, Palo Alto, CA USA. Hop Henri Mondor, F-94010 Creteil, France.Buyse, M, Limburgs Univ Ctr, Diepenbeek, Belgium.