Background:Quality of life (qol) is important for oncology patients, especially for those with late-stage disease. The present study was initiated to address the lack of published prospective data about the qol benefits of trifluridine/tipiracil (ftd/tpi) compared with best supportive care (bsc) in patients with refractory metastatic colorectal cancer (mcrc).Methods:This prospective, cross-sectional, non-interventional study used multidimensional validated scales to evaluate patient-reported qol in two study cohorts of patients and also to measure differences in mcrc-related symptoms and pain in a real-world clinical setting.Results:Our findings demonstrate that patients with refractory mcrc report better overall qol when treated with ftd/tpi than with bsc alone. In that population, statistically significant differences in mean qol measures favoured ftd/tpi over bsc for physical symptom distress, psychological distress, activity impairment, overall valuation of life, and symptomatology. The overall better qol for patients receiving ftd/tpi implies that treatment was well tolerated and was associated with a lower symptom burden. No significant differences for pain were observed between the groups.Conclusions:This study suggests that ftd/tpi is a well-tolerated option for the treatment of patients with refractory mcrc, showcasing the value of capturing real-world qol data in routine clinical practice.

Pembro, a PD-1 inhibitor, has limited efficacy in microsatellite stable (MSS)/mismatch repair-proficient (pMMR) mCRC. The phase Ib KEYNOTE-651 study (NCT03374254) evaluated pembro + mFOLFOX7 (cohort B) or FOLFIRI (cohort D) in pts with MSS/pMMR mCRC. Updated results with more pts and additional follow-up are presented. Pts were ≥18 y with MSS/pMMR mCRC and no prior systemic chemotherapy (cohort B) or 1 prior fluoropyrimidine + oxaliplatin–based regimen (cohort D). Pts received pembro 200 mg Q3W + mFOLFOX7 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-FU, 2400 mg/m2) Q2W (cohort B) or pembro 200 mg Q3W + FOLFIRI (irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; 5-FU, 2400 mg/m2) Q2W (cohort D). Each cohort comprised 2 phases: dose finding (part 1) and dose confirmation (part 2). Primary end points: safety/tolerability and recommended phase II dose (RP2D). Secondary end point: ORR by investigator assessment. Data are presented for parts 1 and 2 combined. 31 pts in cohort B and 32 pts in cohort D received treatment; median (range) follow-up was 41.9 mo (13.3-101.9) in cohort B and 43.0 mo (5.3-100.0) in cohort D. Treatment was discontinued in 19 pts (61%) in cohort B and 20 pts (63%) in cohort D, mostly due to PD (cohort B: n=11, 36%; cohort D: n=14, 44%). There was 1 dose-limiting toxicity (grade 3 small-intestine obstruction) in cohort D. RP2D was defined as the starting dose level for both cohorts. All pts had ≥1 treatment-related adverse event (TRAE). Grade ≥3 TRAEs occurred in 18 pts (58%) in cohort B and 17 pts (53%) in cohort D. Most common TRAEs: neutrophil count decreased (23%) in cohort B and neutropenia and diarrhea (13% each) in cohort D. There were no grade 5 TRAEs. Confirmed ORR was observed in 18 pts (58%; 1 CR, 17 PRs) and 5 pts (16%; 5 PRs) in cohorts B and D, respectively; disease control rate was 94% and 63%, respectively. Median (range) duration of response was 10.3 mo (3.5+ to 18.5+) in cohort B and 17.4 mo (1.6+ to 20.2) in cohort D. Pembro + mFOLFOX7 or FOLFIRI was safe and tolerable in pts with MSS/pMMR mCRC. Preliminary evidence of efficacy was seen in both cohorts.

GEM and Nab-P is a standard first line therapy for mPDAC based on the MPACT Trial. D is a human monoclonal antibody (mAb) that inhibits binding PD-L1 to its receptor. T is a mAb directed against CTLA-4. PA.7 is designed to evaluate whether combining PD-L1 and CTLA-4 inhibition with GEM and Nab-P increases treatment efficacy. This randomized phase II study (NCT02879318) assessed the efficacy and safety of GEM, Nab-P, D, and T (arm A) vs GEM and Nab-P (arm B) in patients (pts) with mPDAC (n=191). Pts with untreated mPDAC and good performance status (ECOG PS 0-1) were eligible. A safety run in was conducted for 11 pts receiving GEM, Nab-P, D and T. The study then randomized 180 pts in a 2:1 ratio to receive GEM (1000mg/m2 D1, 8, 15); Nab-P (125mg/m2 D1, 8, 15); D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles vs. GEM and Nab-P alone. The primary endpoint is overall survival (OS); secondary endpoints include progression free survival (PFS), safety, overall response rate (ORR) and quality of life. 180 pts were randomized (119 to arm A and 61 to arm B) between April 2017 and July 2018. Baseline characteristics were well balanced. With a median (med) follow-up of 28.5 months (mo) there was no significant difference in OS (med 9.8 mo in arm A vs. 8.8 mo in arm B, Hazard Ratio (HR)=0.94, 90% confidence interval (CI) 0.71-1.25, p=0.72). There was no significant difference in PFS (med 5.5 mo vs 5.4 mo respectively, HR=0.98, 90% CI 0.75-1.29, p=0.91). ORR was not significantly different, 30.3% vs. 23.0% respectively (Odds Ratio=1.49, 90% CI 0.81-2.72, p=0.28). Disease control rate (DCR) was 70.6% vs 57.4% respectively (difference=13.2%, 90% CI 0.7-25.7%, p=0.096). The only significant difference in grade 3 or greater adverse events was lymphopenia (38% vs 20% respectively, p=0.02). The addition of dual immune checkpoint inhibitors to Gem and Nab-P did not result in a significant improvement in OS, PFS, or ORR. There is a trend to improved DCR. Correlative analyses to assess biomarkers that may predict immune sensitivity in this setting are underway.

Background FOLFIRINOX (FFX) and Gemcitabine with nab-Paclitaxel (GN) are both proven to be superior to Gemcitabine in first line treatment for advanced pancreatic cancer (APC). However, there has been no phase 3 randomized controlled trials to prove FFX is superior to GN in APC. This population-based cohort study was conducted to compare efficacy and safety profiles of the two standard regimens in APC. Methods In this retrospective cohort study, we evaluated all newly diagnosed patients (pts) with APC who received either FFX or GN as first line therapy during 2010-2018 at three Canadian institutions. The primary objective was to assess survival. Secondary objective was to compare safety profile of the two regimens. Kaplan Meier method and log-rank test were used for survival curves. Results There were 231 eligible pts identified: 143 received FFX and 88 received GN. FFX pts were slightly younger than GN (median age: 62 (IQR: 56-67) vs 66 (IQR: 58-73) respectively). There were predominantly more males: FFX 89 (62.2%) vs GN 46 (52.3%). WHO performance status (PS) of 0 were 38 (28.4%) vs 14 (16.5%) and 1 were 90 (67.2%) vs 65 (76.5%) respectively. The median progression-free survival (PFS) of FFX was 5.5 months (mts) (95% CI: 5.0-6.7) vs 5.1 mts (95% CI: 3.8-7.1) with GN (p = 0.37). The median overall survival (OS) with FFX was 9.3 mts (95% CI: 7.5 – 11.1) vs. 10.2 mts (95% CI: 6.8-11.3) with GN (p = 0.81). On multivariate analysis chemotherapy regimen was not correlated with PFS or OS. There were more grade 3-4 toxicity in FFX vs GN group: diarrhea – 22 (15.4%) vs 3 (3.4%) (p = 0.004), nausea – 20 (14%) vs 6 (6.8%), vomiting – 13 (9.1%) vs 6 (6.8%), peripheral sensory neuropathy (PSN) – 8 (5.6%) vs 3 (3.4%), thrombocytopenia – 28 (19.6%) vs 5 (5.7%) (p = 0.003) respectively. Gr 3-4 neutropenia rates were similar in both regimens: 23 (16%) in FFX vs 15 (17%) in GN. Conclusions Our results revealed that FFX or GN had comparable survival and safety profiles. Given lower Gr 3-4 toxicity profile of GN regimen, GN is likely preferable choice for majority of pts. FFX could be reserved for young high performance pts. Legal entity responsible for the study Segal Cancer Centre Jewish General Hospital. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Assessment of the clinical benefit of cancer treatments can be highly subjective, influenced by both perspective and context. Such assessments are required in regulatory and policy decision-making, but consistency between jurisdictions is often lacking. Clear and consistent standards for determining when a treatment offers a meaningful benefit, relative to the current standard of care, can help to address issues of equity and transparency in health technology assessment. For metastatic colorectal cancer (MCRC), no standardized Canadian definition of clinically meaningful benefit has yet been proposed. Colorectal Cancer Canada therefore convened a group of medical oncologists expert in colorectal cancer to review the literature about clinical significance. The resulting consensus is intended to apply to any therapeutic agent being considered in the setting of chemotherapy-refractory MCRC. It was agreed that overall survival is the appropriate measure of clinical efficacy in chemorefractory MCRC. As quantitative targets for efficacy, an improvement of 2 months or more in median overall survival or a hazard ratio for survival of 0.75 or lower (or both) are proposed as the threshold for clinically meaningful benefit. That threshold could be influenced by a treatment’s effect on quality of life. Treatment toxicity is also relevant to the assessment of clinical benefit in this setting, specifically when significant differences in treatment tolerability are evident.

Abstract Background Pembro, a PD-1 inhibitor, confers durable benefit in many tumor types but has limited efficacy in non–microsatellite instability–high (MSI-high)/pMMR mCRC. Chemotherapies that include 5-fluorouracil (5-FU), oxaliplatin and irinotecan, which are commonly used to treat mCRC, may modulate intrinsic tumor immunogenicity and sensitize tumors to immunotherapy agents. In the phase 1b KEYNOTE-651 study (NCT03374254), pembro + mFOLFOX7 (cohort B) or pembro + FOLFIRI (cohort D) was evaluated in patients with non–MSI-high/pMMR mCRC. Methods Patients were ≥18 years with non–MSI-high/pMMR mCRC, Eastern Cooperative Oncology Group performance status 0/1, and no prior systemic chemotherapy for stage IV mCRC (cohort B) or 1 prior therapy including a fluoropyrimidine + oxaliplatin-based regimen (cohort D). Patients received pembro 200 mg every 3 weeks (Q3W) + mFOLFOX7 (oxaliplatin [85 mg/m2]; leucovorin [400 mg/m2]; 5-FU [2400 mg/m2]) Q2W (cohort B) or pembro 200 mg Q3W + FOLFIRI (irinotecan [180 mg/m2]; leucovorin [400 mg/m2]; 5-FU [2400 mg/m2]) Q2W (cohort D). Primary objectives were safety/tolerability and establishment of the recommended phase 2 dose (RP2D); the secondary objective was objective response rate. Results At data cutoff (Feb 18, 2019), 15 patients in cohort B and 16 in cohort D started treatment; median follow-up was 6.8 months (cohort B) and 5.7 months (cohort D). Treatment was discontinued in 4 patients (27%) in cohort B (adverse event [AE], n = 1 [7%]; PD, n = 3 [20%]) and 9 patients (56%) in cohort D (AEs, PD, patient withdrawal; n = 3 [19%] each). There was 1 dose-limiting toxicity in cohort D: grade 3 small-intestinal obstruction. See RP2Ds for cohorts B and D in the Methods section. All patients had ≥1 treatment-related AE (TRAE). Grade 3 TRAEs occurred in 8 patients each in cohort B (53%) and cohort D (50%), most commonly anemia and neutropenia (13% each) in cohort B and neutropenia, diarrhea, fatigue, and leukopenia (13% each) in cohort D. There were no grade 4-5 TRAEs. Efficacy results will be presented. Conclusions Pembro in combination with mFOLFOX7 or FOLFIRI was safe and tolerable in patients with mCRC. Clinical trial identification NCT03374254; Release date: December 15, 2017. Editorial acknowledgement Jacqueline Kolston, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA); Funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Legal entity responsible for the study Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Array BioPharma. Funding Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Array BioPharma. Disclosure R. Kim: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Research grant / Funding (institution): Eisai. J. Kortmansky: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Roche. L. Wong: Research grant / Funding (institution): Astellas Pharma Global Development, Inc./Astellas US, Inc.; Research grant / Funding (institution): BeiGene, Ltd; Research grant / Funding (institution): Exelixis, Inc.; Research grant / Funding (institution): Merck; Research grant / Funding (institution): NovoCure, Inc.; Research grant / Funding (institution): Pierre Fabre Medicament; Research grant / Funding (institution): PledPharma AB; Research grant / Funding (institution): SynCore Biotechnology Co., Ltd.; Research grant / Funding (institution): Halozyme, Inc.; Research grant / Funding (institution): Pharmacyclics, Inc.; Research grant / Funding (institution): TESARO; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Array. M. Tehfe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self): Ipsen; Advisory / Consultancy: BMS; Advisory / Consultancy: Takeda; Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Taisho. J.J. Li: Full / Part-time employment: Merck & Co., Inc. M. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. C. Mayo: Full / Part-time employment: Merck & Co., Inc. P. Marinello: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. E. Chiorean: Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Halozyme; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Array; Advisory / Consultancy: Five Prime; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Halozyme; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Ignyta/Roche; Research grant / Funding (institution): Stemline; Research grant / Funding (institution): Macrogenetics. All other authors have declared no conflicts of interest.

Introduction: We have previously defined ‘next generation specimens’ as longitudinal biopsy samples collected at different time points during the disease trajectory, in a specific treatment context, either for discovery research or to guide clinical decisions (Basik, M. et al. Nat Rev Clin Oncol. 2013). The objective of the present study was to track tumor evolution at the copy number (CN) level and capture emerging resistance mechanisms in metastatic colorectal cancer (mCRC) using a standardized collection of high-quality metastasis samples, at baseline and at the time of clinical resistance, in the context of a phase IV multicenter clinical trial (NCT00984048). Methods: One hundred and forty fresh frozen liver metastasis (LM) specimens collected at baseline (pre, n = 97) and at the time of clinical resistance (post, n = 43) from 119 mCRC patients undergoing standard first-line therapy were profiled using whole exome sequencing and characterized for CN variation using Nexus Copy Number software. RNA sequencing data available for the same sample set allowed filtering the CN aberration (CNA) candidates for mRNA correlation in each analysis performed. Objective response was attributed based on the RECIST v1.0 criteria. Genomic Identification of Significant Target in Cancer (GISTIC) test was used to identify focal CNA. CNA frequency reported as being significantly different between 2 groups met a minimum p-value of 0.005 on a two-tailed Fisher’s exact test. The log-rank test was used to identify CNA associated with progression-free survival (PFS). The threshold used for significance was permutated p-value < .005. Results: The CN variation landscape of 97 pre LM samples confirmed the most common chromosome (chr) arm amplifications being on chr 7p, 7q, 8q, 13q, and 20q and the most frequent deletions on chr 1p, 1q, 4p, 4q, 8p, 17p, 18p, 18q, and 22q. Twenty-nine focal aberrations were also identified by GISTIC. Comparative analyses identified 22 focal CNA with significantly different frequencies between pre- and post- samples. The comparison between partial responder (PR, n = 47) and intrinsically resistant (IRES, n = 5) lesions revealed 34 CNA with different frequencies at baseline. Acquired resistant (ARES) and IRES post-samples (n = 8) showed significant enrichment in 36 CNA compared to pre-sample (n = 97), and these CNA were not captured when PR (n = 10) post-samples are compared to pre-samples. One hundred thirty-seven CNA regions were found to be significantly associated with PFS. Interrogation of primary tumors and LM data available in public databases validated the predictive potential of 18 regions and also revealed the metastasis specificity of 15 of them. Candidate genes in these regions with concordant genomic/transcriptomic aberrations were identified. Conclusion: Our effort to collect and profile next-generation biospecimens provided global genomic and transcriptomic data of the largest LM cohort to date. By analyzing the association between molecular aberrations and patient outcomes, we identified novel biomarker candidates predictive of drug response in LM samples, supporting the utility of collecting metastatic samples in clinical settings.

ResultsOverall 447 patients were included; 300 in the discovery cohort (median follow-up: 4.2 years) and 147 in the validation cohort (median follow-up: 3 years).Between the two cohorts, there were no significant difference in the 3-year DC (88% [95% CI: 84%-91%] vs. 84% [95% CI: 77%-89%], p=0.16) or OS (72% [95% CI: 67%-77%] vs. 69% [95% CI: 61%-77%], p=0.26).The Multivariable analysis identified pN2-3 and histological grade 2-3 (G2-3) as DM predictors.The high-risk group included patients who had both poor predictors (pN2-3 and G2-3), while low-risk group consisted of patients who had one or no poor predictors.In the discovery cohort, the 3-year DC rate was 78% (95% CI: 70%-84%) and 97% (95% CI: 92%-99%) in high-and low-risk groups respectively (p<0.001), with the concordance index (c-index) of 0.72.In the validation cohort, the risk group classification performed similarly (3-year DC: 69% [95% CI: 54%-79%] vs. 95% [95% CI: 87%-98%], p<0.001) with the c-index value of 0.73.The 3-year OS for the high-vs.low-risk group was 85% (95% CI: 79-91%) vs. 95% (95% CI: 91%-98%) in the discovery cohort (p<0.001), and 74% (95% CI: 63-86%) and 93% (95% CI: 87%-99%) in the validation cohort (p<0.001). ConclusionThe proposed classification allowed for the definition of a high risk group of DM with poor survival.This validated model (G2-3/pN2-3) could be used to identify OSCC patients who may benefit from: 1) more aggressive screening for DM (before initiating the treatment) in order to avoid unnecessary or inappropriate management, 2) experimental systemic treatment intensification to impact development of DM, and 3) a more aggressive post-treatment surveillance schedule for early detection of DM and consideration of experimental ablative treatments for oligometastatic or early systemic treatment for non-oligometastatic disease.

Introduction: Approval of pembrolizumab as treatment for adult and pediatric patients with unresectable or metastatic previously treated MSI-H or mismatch repair–deficient cancer, regardless of tumor type or site, was partly based on data from cohort A of the phase 2 KEYNOTE-164 (NCT02460198) study of patients with MSI-H colorectal cancer (CRC) after ≥2 prior lines of standard therapy. Data are presented herein from cohort B of KEYNOTE-164, which was conducted to evaluate pembrolizumab in patients with metastatic MSI-H CRC previously treated with ≥1 line of therapy. Methods: Cohort B of the KEYNOTE-164 study enrolled patients with metastatic CRC who had locally confirmed MSI-H status per immunohistochemistry or polymerase chain reaction and had received ≥1 prior line of therapy (irinotecan, oxaliplatin, fluoropyrimidine, or anti-vascular endothelial growth factor/endothelial growth factor receptor). Patients received pembrolizumab 200 mg every 3 weeks (Q3W) for 2 years or until progression, unacceptable toxicity, or withdrawal of consent. Tumor response was assessed per RECIST v1.1 by independent review Q9W. End points included objective response rate (ORR) (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary). Results: Sixty-three patients were enrolled; median age was 59 years (range: 23-83); 52% were male. Most patients (94%) had ≥1 prior therapy for advanced disease; median number of prior therapies was 2. As of September 12, 2017, median follow-up was 12.6 months (range: 0.1-15.4). ORR was 32% (95% CI, 21-45), with 2 complete responses and 18 partial responses. Median DOR was not reached (NR); 95% of responses were ongoing; and DOR for 75% of responders was ≥6 months. Median PFS was 4.1 months (95% CI, 2.1-NR) and median OS was NR. The 12-month PFS rate was 41% and the 12-month OS rate was 76%. Forty (64%) patients experienced treatment-related adverse events (AEs) of any grade, most commonly (≥10%) fatigue (18%), hypothyroidism (16%), and hyperthyroidism (11%). Seven (11%) patients had grade ≥3 treatment-related AEs of anemia, thrombocytopenia, diarrhea, pneumatosis intestinalis, pneumonitis, syncope, arthritis, and vasculitis (n = 1 each). There were no treatment-related deaths. Twenty (32%) patients had immune-mediated AEs of any grade. Two (3%) patients had grade ≥3 immune-mediated AEs of pneumonitis and colitis (n = 1 each). Conclusion: Pembrolizumab demonstrated durable antitumor activity with a safety profile that was manageable in cohort B of KEYNOTE-164, which was conducted to evaluate patients with MSI-H CRC whose disease progressed after ≥1 line of prior therapy.

Introduction: Patients with cancer are at an increased risk of developing venous thromboembolism (VTE), an important cause of morbidity and mortality in this population. In response to the need for better management of cancer-associated thrombosis (CAT), national and international practice guidelines have been developed, such as those published by ASCO, ESMO, and the NCCN. However, it is unclear how adherent clinicians are to these guidelines.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

The Ph 3 VELOUR study demonstrated that addition of aflibercept (ziv-aflibercept [USA]) to fixed-dose FOLFIRI improved survival outcomes & response rates in mCRC pts treated with prior oxaliplatin-based chemotherapy. The global ASQoP study (NCT01571284) is a single-arm, open-label trial in a population similar to VELOUR, evaluating QoL and safety in a closer to real-life setting. Here, we report safety data from the 5th interim analysis of ASQoP. ASQoP enrolled mCRC pts (ECOG PS 0–1) with prior oxaliplatin-based therapy, regardless of prior bevacizumab (Bev) therapy. Pts received 4 mg/kg aflibercept & FOLFIRI on d1 of a 2-wk cycle, until disease progression (PD), unacceptable toxicity, death or investigator/pt decision. Initial FOLFIRI dose & subsequent modifications were at physician's discretion. Adverse events (AEs) were evaluated using CTCv4.03. At data cut-off (7 Mar 2016), the safety population (≥1 full treatment cycle) comprised 779 pts: male 59.7%; ECOG PS = 0 62.0% (VELOUR 57.0%); median age 61.0 y (VELOUR 61.0 y); age ≥65 y 39.0%; median time from diagnosis 13.4 mo; prior Bev 46.2%; prior thrombovascular events/presence of CV risk factors 54.4%. In total, 774 pts discontinued treatment, mostly due to PD (52.3%) or AEs (26.7%). Among pts who discontinued treatment, the median no. of cycles was 7 (VELOUR 9 cycles); median duration of exposure was 16.6 wks (VELOUR 21.4 wks). A summary of the AEs in ASQoP and VELOUR are in the table. ASQoP is an ongoing study; these results are not final. Aflibercept-related toxicity was similar in ASQoP and VELOUR. The frequency of some AEs appears lower in ASQoP, which may reflect more flexible FOLFIRI dosing, or more routine in AE management. Overall, the safety profile in ASQoP was consistent with the known safety profile of aflibercept/FOLFIRI, with no new safety signals identified.Tabled 1ASQoP – 5th interim analysis Aflibercept + FOLFIRI (n = 779)VELOUR flibercept + FOLFIRI (n = 611)Patients (%)All gradesGrade 3–4Grade 4All gradesGrade 3–4Grade 4Any TEAE98.778.218.099.283.521.4Selected TEAEs of any grade in ≥20% of patientsDiarrhoea (PT)61.215.30.369.219.30.3Asthenic conditions (HLT)57.813.6060.416.90.8Hypertension (grouped term)48.424.1041.419.30.2Stomatitis and ulcerations (HLT)43.510.70.154.813.70.2Infections and infestations (SOC)31.311.72.146.212.31.3VEGF-associated eventsVenous thromboembolic events (grouped term)6.24.10.99.37.94.7Arterial thromboembolic events (grouped term)2.30.80.32.61.81.0Gastrointestinal perforation (grouped term)1.41.40.60.50.50.3Fistula (gastrointestinal origin) (grouped term)1.80.801.10.30Laboratory abnormalitiesNeutropenia60.5*30.5*9.7*67.8**36.7**13.6**Proteinuria60.17.30.662.27.90.3*n = 744; **n = 603 HLT, high-level term; PT, preferred term; SOC, system organ class; TEAE, treatment-emergent adverse event Open table in a new tab