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The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA-ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium-term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, ≥Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%-79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%-73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real-world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns.

BACKGROUND Adding pertuzumab to trastuzumab in patients (pts) with HER2+ breast cancer improves pathological complete response (pCR) rates. Pertuzumab + trastuzumab + chemotherapy is approved in Australia as neoadjuvant therapy in early stage (>2 cm or node positive), locally advanced and inflammatory HER2+ breast cancer. This study captured real-world data on the safety and effectiveness of pertuzumab in the neoadjuvant setting. METHODS PeRSIA (ML39622) is a secondary data use non-interventional study of pts initiating neoadjuvant pertuzumab treatment for non-metastatic HER2+ breast cancer. The primary objective is to assess the effectiveness and safety of neoadjuvant pertuzumab when added to trastuzumab in the real-world setting. Deidentified data obtained from the pts’ medical notes were captured using REDCaP, hosted at the Walter and Eliza Hall Institute of Medical Research. This analysis reports the co-primary endpoints of breast pCR (bpCR) with or without in situ disease (ypT0/is or ypT0), total pCR (tpCR) with or without in situ disease (ypT0/is ypN0 or ypT0 ypN0), and the incidence of adverse events (AEs) related to pertuzumab. Secondary objectives include describing rates of breast and nodal surgery, relapse free survival (RFS) and overall survival (OS). RESULTS Ninety five pts receiving neoadjuvant pertuzumab were enrolled between March 2018 and July 2019, with data available for all pts. HER2-targeted neoadjuvant treatment was completed in 91 pts (95.8%) with a median number of 4 cycles [range 1-6] of pertuzumab and 5 cycles [range 1-6] of trastuzumab. Four pts did not complete the planned neoadjuvant therapy due to early CR (n=1), and pertuzumab-related AEs (n=3). The most common neoadjuvant chemotherapy regimens were sequential anthracyclines + taxanes (n=59, 62.1%) and single agent taxane (n=29, 30.5%). Surgery was performed in 92 pts (96.8%). Three pts did not proceed to surgery due to patient decision (n=1), physician decision (n=1), and development of a new non-breast cancer which resulted in death (n=1). Of those pts that underwent surgery, 65/92 (70.7%) had a bpCR and 59/92 (64.1%) had a tpCR. All pts who did not achieve a pCR obtained a partial response (33/92, 35.9%). Total pCR was seen in 27/34 (79.4%) pts with hormone receptor-negative and 32/58 (55.2%) pts with hormone receptor-positive cancers. 27/95 (28.4%) pts experienced an AE related to pertuzumab; diarrhea (21.1%) and rash (4.2%) were the most common AEs. Three pts (3.2%) discontinued pertuzumab due to an AE: cardiac toxicity, diarrhea and rash (n=1), cardiac toxicity (n=1), and diarrhea and sepsis (n=1). Following surgery, 93/95 (97.9%) patients received adjuvant HER2-directed therapy, and 4/95 (4.2%) received adjuvant chemotherapy. After a median follow-up from diagnosis of 21.2 [14.0-83.9] months, the RFS and OS were 92.6% and 99.0% respectively. Disease recurrence occurred in 6 pts (distant n=4, contralateral n=2). CONCLUSIONS This is the first multicenter, observational study of neoadjuvant therapy based on dual blockade with pertuzumab and trastuzumab for HER2+ non-metastatic breast cancer in Australia. The pCR rates achieved were numerically higher than previously reported in clinical trials. There were no significant safety findings outside of the expected safety profile for pertuzumab. Acknowledgments: Study sponsored by Roche Products, Pty. Limited. Theresa Wade (WriteSource Medical) provided medical writing. Table: Baseline Characteristics (n=95)CharacteristicNumber (%)Age, median (range)50.3 (24.4 -82.1)Charlson Comorbidity Index- 077 (81.1)- 19 (9.5)- 2 +9 (9.5)Tumour Size12 (12.6)- T156 (59.0)- T225 (26.3)- T3- Unreported2 (2.1)Tumour Grade- 10 (0)- 231 (32.6)- 362 (65.3)- Unreported2 (2.1)Nodal status- Positive63 (66.3)- Negative32 (33.7)Hormone Receptor Status- HR+60 (63.2)- HR-35 (36.8)Median baseline left ventricular ejection fraction (range)65.0% (35-79)Cardiac risk factors- 053 (55.8)- 122 (23.2)- 2+20 (21.1) Citation Format: Sheau Wen Lok, Richard De Boer, Sallt Baron-Hay, Peter Button, Bianca Devitt, Benjamin Forster, Peter Fox, Michael Harold, Sahisha Ketheeswaran, Ganessan Kichenadasse, Belinda E Kiely, Gavin Marx, Louise Nott, Laura Pellegrini, Ali Tafreshi, Peter GIbbs. Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-38.

Background: The addition of pertuzumab to trastuzumab for patients (pts) with HER2 +ve breast cancer results in higher rates of pathological complete response (pCR);although, it is not yet known if this translates into improved survival outcomes. In May 2016 pertuzumab was approved in Australia by the Therapeutic Goods Administration, in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of locally advanced and inflammatory HER2+ve breast cancer; and in September 2018, for early stage (>2cm diameter or node positive) disease. This study aims to capture real world data on the safety and effectiveness of pertuzumab in the neoadjuvant setting. Methods: PeRSIA (ML39622) is a secondary data use non-interventional study of pts initiating or considering pertuzumab treatment in the neoadjuvant setting for non-metastatic HER2+ breast cancer. The primary objective is to assess the incidence rates of all adverse events (AEs) related to pertuzumab and the effectiveness of neoadjuvant pertuzumab when added to trastuzumab, in the real world setting. De-identified data obtained from the pts’ medical notes by the treating physician, were deposited to a centralized data capture tool (REDCaP), hosted at the Walter and Eliza Hall Institute of Medical Research. This interim analysis reports the co-primary endpoints of breast pCR (bpCR) with or without in situ disease (ypT0/is or ypT0), total pCR with or without in situ disease (ypT0/is ypN0 or ypT0 ypN0), and the incidence of AEs related to pertuzumab. Secondary objectives include rates of breast or nodal surgery, relapse free survival (RFS) and overall survival (OS). Results: Ninety pts receiving neoadjuvant pertuzumab were enrolled for data capture between March 2018 and June 2019. Sixty-nine of these pts had data available for interim analysis by June 18th 2019 (Table). HER2-targeted neoadjuvant treatment was completed in 65/69 pts (94.2%) with a median [min-max] duration of 4 [1-6] cycles of pertuzumab and 5 [1-6] cycles of trastuzumab, and chemotherapy was administered in all 69 pts. The most common neoadjuvant chemotherapy regimens were taxanes + anthracyclines (n=30, 43.5%) and single agent taxane (n=26, 37.7%). Surgery was performed in 66/69 pts (95.7%). The bpCR was 71.2% and the total pCR rate was 66.7%. All pts who did not achieve a pCR obtained a partial response (28.8%). Total pCR was achieved by 20/26 (76.9%) hormone receptor-negative and 24/40 (60.0%) hormone receptor-positive pts. Three pts (4.3%) experienced at least one pertuzumab-related AE [cardiac toxicity (n=1, 1.4%), diarrhea (n=2, 2.9%), rash (n=1, 1.4%) and (sepsis n=1, 1.4%)] and all ceased pertuzumab. RFS and OS were 97.1% and 98.6% respectively, with a median follow up time from diagnosis of 16.1 [4-36.4] months. One patient did not undergo surgery due to a new non-breast cancer which resulted in death. Conclusion: This is the first multicenter, prospective, observational study to report pCR with pertuzumab in real world clinical practice in Australia. Neoadjuvant therapy based on dual blockade with pertuzumab and trastuzumab for HER2+ non metastatic breast cancer achieved a total pCR rate of 66.7% and bpCR rate of 71.2%, which was numerically higher than previously reported in clinical trials. There were no significant safety findings outside of the accepted safety profile for pertuzumab. Acknowledgment: Study sponsored by Roche Products, Pty. Limited Table: Patient and Tumor CharacteristicsCharacteristicNumber (%)Age51.8 (25.9-82.1)Charlson Comorbidity Index058 (84.1)18 (11.6)≥23 (4.4)Tumor Size (Clinical/Radiological staging)T1 (5 cm)14 (20.3)Unknown2 (2.9)Tumor Grade10 (0)220 (29.0)347 (68.1)Unknown2 (2.9)Nodal Status (Clinical/Radiological)Node positive46 (66.7)Node negative23 (33.3)Hormone Receptor StatusHR+42 (60.9)HR−27 (39.1)Median baseline left ventricular ejection fraction65%Patient cardiac risk factorsNo risk factor40 (58.0)1 risk factor14 (20.3)≥2 risk factors15 (21.7) Citation Format: Sheau Wen Lok, Richard De Boer, Sally Baron-Hay, Fran Boyle, Peter Button, Belinda Castles, Bianca Devitt, Peter Fox, Michael Harold, Ganessan Kichenadasse, Belinda E Kiely, Gavin Marx, Louise Nott, Laura Pellegrini, Ali Tafreshi, Peter Gibbs. Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia: Interim analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-15.

Background: HER2 targeted therapies, such as trastuzumab, pertuzumab and trastuzumab-emtansine (TDM-1), have improved survival of patients (pts) with HER2+ metastatic breast cancer (MBC). In the pivotal phase III study of pertuzumab/trastuzumab/docetaxel in MBC (NCT00567190), only 10% of pts received prior trastuzumab, whereas in modern practice the majority of recurrent HER2+ MBC pts have received neo(adjuvant) trastuzumab [NAT]. Survival outcomes in the real world setting have not been well described. Methods: Pts were part of a prospective national registry collecting clinicopathologic, treatment and outcome data for HER2+ MBC pts diagnosed between 10/2006 and 1/2019. Survival was estimated by the Kaplan-Meier method and compared among groups by log-rank test. A multivariable analysis was used to assess the impact of prior trastuzumab-use on survival. Analysis was stratified by estrogen receptor (ER) status to exclude the impact of concurrent endocrine therapy in the ER positive (ER+) subgroup. The TABITHA registry is sponsored by BioGrid Australia with financial support from Roche Products Pty Limited. Results: Of 254 HER2+ MBC pts in the registry, 225 received HER2 directed therapy in the first-line advanced disease setting and were included for analysis. Median age was 58 years, 100 (44%) had de novo metastatic disease, 131 (58%) had ER+ disease and 24 (11%) had brain metastases. Of the 125 (56%) pts with recurrent disease, 89 (71%) pts received NAT. First-line HER2 therapy was pertuzumab plus trastuzumab in 176 (78%), trastuzumab in 38 (17%), TDM-1 in 9 (4%), and lapatinib or pertuzumab alone in single pts ( The response rate to anti-HER2 therapy among all MBC pts evaluable for response was 42% in pts who received NAT, and 53% in pts who did not (p=0.20). Median progression free survival (PFS) was 16.4 months and 22.6 months, in pts who were trastuzumab-treated and trastuzumab-naïve, respectively (HR 1.44 [95%CI 0.99 - 2.10], p=0.05). The median overall survival (OS) from first-line HER2-directed therapy for MBC was 41.2 months in pts who had prior NAT, and 52.0 months in trastuzumab-naïve pts (HR 1.73 [95%CI 1.04 - 2.86], p=0.03). On multivariable analysis, prior trastuzumab-exposure was no longer significantly associated with survival. Factors significantly associated with PFS were ER status (HR 0.63, p=0.02) and age (HR 1.02, p=0.04), while only age was significantly associated with OS (see table). Among the subset of 93 ER negative (ER-) pts, prior NAT was significantly associated with inferior PFS (HR 1.97 [95%CI 1.11 - 3.52], p=0.02) and OS (HR 2.13 [95% CI 1.00 - 4.57], p=0.046). Multivariable analysis found only age and presence of brain metastases to be significantly associated with OS in the ER- subgroup. NAT exposure did not impact on PFS (HR 1.15, [95% CI 0.70 - 1.90], p=0.58) or OS (HR 1.37, [95% CI 0.68 - 2.73], p=0.37) in ER+ pts. Conclusions: In pts with HER2+ MBC, receipt of NAT was associated with inferior survival when HER2 targeted therapy was used in the metastatic setting on univariate analysis, but this finding was not seen in a multivariable analysis. Furthermore, the impact of NAT was only observed in the subset of pts with ER- tumors, raising the possibility that the disease-course in ER+ subgroup is not entirely HER2 driven. Survival rates of these HER2+ MBC pts treated in the community are comparable to that reported in clinical trials. Cox proportional hazard models for OS in MBC on HER2-targeted therapyUnivariableMultivariableHR95% CIPHR95% CIPAdjuvant trastuzumab Y vs N1.731.04 – 2.850.031.370.64 – 2.940.42De novo metastatic disease Y vs N0.610.37 – 1.020.060.810.38 – 1.730.59Estrogen receptor positive vs negative0.880.53 – 1.440.600.690.41 – 1.180.18Brain metastases Y vs N1.800.88 – 3.670.111.960.90 – 4.260.09Age (years)1.021.00 – 1.040.051.031.01 – 1.060.003 Citation Format: Yada Kanjanapan, Dan Tran, Sheau Wen Lok, Peter Gibbs, Richard De Boer, Belinda Yeo, Sally Greenberg, Frances Barnett, Louise Knott, Gary Richardson, Rachel Wong, Michelle Nottage, Ian Collins, Javier Torres, Janine Lombard, Julie Johns, Michael Harold, Laeeq Malik. Impact of prior (neo)adjuvant trastuzumab exposure on the efficacy of HER2 targeted therapy for metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-13.

750 Background: Optimal sequencing of therapies in synchronous metastatic rectal cancer (SMRC) remains unknown. Aim: To compare sequencing of treatment modality and outcomes in SMRC. Methods: Retrospective audit of patients with SMRC registered on the multi-centre Treatment of Recurrent and Advanced Colorectal Cancer database between 1/1/2009 and 30/6/2015. Patients were grouped according to initial treatment mode: chemotherapy (C), chemoradiation (CRT), surgery (S) and best supportive care (BSC). Results: 247 patients were identified: median age was 62yrs, ECOG 0-1 87%, male 64%, 1-2 metastatic sites 86% (liver 56%) and treatment intent was curative in 14%. Median follow-up was 19m. Primary tumour resection occurred in 95 patients (38%). Compared to no resection, these patients had improved median OS (41 vs 16 months; p < 0.0001) and PFS (15 vs 10 months; p < 0.0001). There was no difference in outcome with varying treatment combinations and sequences of S with CRT/C (p > 0.05). For unresected patients, the most common initial treatment was C (30%). Any active treatment was associated with better OS compared to BSC (6.4m): C (16.1m, p < 0.0001), CRT (20.6m, p = 0.001) and C&CRT (21.8m, p < 0.0001). Most active treatments were associated with better PFS compared to BSC (6.4m): C (10.8m, p = 0.015) and C&CRT (10.6m, p = 0.012). There was no significant PFS difference comparing BSC to CRT (p = 0.25). There were no OS nor PFS differences between: comparisons of C, CRT and C&CRT (p > 0.05). Initial treatment strategies were compared for 129 patients receiving multimodal therapy, where 22 (17%) had initial treatment with C (60% subsequent resection) compared to 85 (66%) commencing with CRT (70% subsequent resection). Commencing with CRT was associated with a longer OS compared to C (31 vs 21 months; p = 0.014). Conclusions: For patients undergoing primary tumour resection, no difference in outcomes were demonstrated with the addition of C and/or CRT. For unresected patients, there was a survival benefit associated with active therapy, with no significant difference between C, CRT or C&CRT. This supports the current practice of using these modalities at clinicians’ discretion. Review of patient factors potentially influencing treatment choice is ongoing.

e14518 Background: Variation in outcomes for rectal (RC) and colon (CC) cancer have been reported, particularly in the advanced disease setting. Established differences in patterns of metastatic sp...

572 Background: At initial diagnosis of mCRC, accurate assessment of patient prognosis is critical to defining the optimal initial treatment strategy. While performance status (PS) and number of metastatic sites are presumed surrogates of TB, to date TB assessment has not been formally examined as a potential prognostic marker in mCRC, despite supportive evidence in other malignancies. Methods: We developed a CT-based scoring system for TB on mCRC patients from the TRACC (Treatment of Recurrent and Advanced Colon Cancer) database. Objective (size and number of metastases) and subjective (clinical judgment) scoring systems were used to separate patients into high, moderate, or low TB subsets. Subjective scoring was repeated by a blinded second assessor on a subset of cases. Clinicopathologic correlates with TB were then assessed, along with survival outcomes for each subset. Results: 151 patients were assessed, median age was 68 years and 51% were male. Using subjective scoring, 55 (36%), 33 (22%), and 63 (42%) were categorized to high, moderate, and low TB subsets. Concordance between assessors using subjective scoring for 30 selected cases was 80% (high), 60% (moderate), and 90% (low). Factors correlating with increasing TB (high vs. low) on objective scoring were PS (31 vs 5% ≥ 2, p = 0.0002), number of disease sites (57 vs 9% ≥2, p < 0.0001) and for patients with mCRC at presentation, reduced likelihood of primary CRC resection. Median overall survival was superior in low compared to high TB subsets for subjective (not reached vs. 15.9mths, p < 0.0001) and objective (not reached vs. 14.7mths, p < 0.0001) scores. Survival difference for low vs high TB were maintained on objective scoring even when patients with resectable metastases were excluded (22.7 vs. 11.9mths, p = 0.0017). Conclusions: TB measured subjectively or objectively is associated with overall survival in mCRC, and is a potential novel prognostic marker. Multi-variate analyses will be performed, and an independent validation cohort is being examined. As TB inversely correlated with primary resection for patients with mCRC at presentation, including TB assessment in further analyses of the survival impact of primary CRC resection is one potential application of this measure.

e16516 Background: Cure is potentially achievable in select patients with mCRC with limited metastatic disease to liver and/or lung. To date the peri-operative strategies undertaken by oncologists in routine practice for such pts have not been well documented. Methods: A clinical database recording information on all pts diagnosed with mCRC since July 2009 from 5 hospitals was analysed. Management strategies where a curative-intent resection had occurred; was planned; or was a potential option were compared with those managed with palliative intent. Results: Status at the time of first review regarding systemic chemotherapy (CT) was documented for 354 pts. 15 (4.2%) had undergone curative-intent resection; 37 (10.5%) had a resection planned; 36 (10.2%) were considered potentially resectable if response to treatment was good; and 266 (75.1%) were treated with palliative intent. Only one patient (1.9%) already resected or planned for resection was >ECOG1, compared with 8% (3/36) potentially resectable and 20% (53/266) palliative pts. CT was delivered in 12 (80%) already-resected, 29 (78%) planned for resection, 33 (92%) potentially-resectable and 202 (76%) palliative-intent pts. Combination CT was the dominant strategy, although 5 of 12 (42%) resected pts received single agent treatment. 17% (n=2) resected pts received bevacizumab with CT, compared with 29% (n=18) of planned or potentially-curative pts and 55% (n=112) of those treated with palliative intent. At the time of analysis 17 pts (46%) with a planned resection and 7 (20%) considered potentially curative have had surgery, while 6 (2.3%) where treatment was initially considered palliative have had curative-intent surgery. Conclusions: Treatment strategies for pts with mCRC differ significantly based on the treatment intent, and may be affected by surgical preference and referral pattern. Bevacizumab was less likely to be used for already-resected pts and the use of single agent therapy in this group was also not uncommon. Many pts initially considered resectable do not ultimately undergo resection, whereas occasional ‘palliative’ pts may become resectable, confirming the importance of continued consideration of this option.

682 Background: Cure is potentially achievable in select patients (pts) with mCRC with limited metastatic disease to liver and/or lung. To date the peri-operative strategies undertaken by oncologists in routine practice for such pts have not been well documented. Methods: A clinical database recording information on all pts diagnosed with mCRC since July 2009 from 5 hospitals was analysed. Management strategies where a curative-intent resection had occurred; was planned; or was a potential option were compared with those managed with palliative intent. Results: Status at the time of first review regarding systemic chemotherapy (CT) was documented for 280 pts. 11 (4%) had already undergone curative-intent resection; 31 (11%) had a resection planned; 27 (10%) were considered potentially resectable if their response to treatment was good; and 207 (74%) were treated with palliative intent. No pts already resected or planned for resection were >ECOG 1, compared with 11% (3/27) potentially resectable and 17% (36/207) palliative pts. CT was delivered in 9 (82%) already-resected, 26 (84%) planned for resection, 26 (96%) potentially-resectable and 159 (77%) palliative-intent pts. Combination CT was the dominant strategy, although 7 of 11 (66%) already-resected pts received single agent treatment. No already-resected pts received bevacizumab with CT, compared with 27% (n=14) of planned or potentially-curative pts and 55% (n=88) of those treated with palliative intent. At the time of analysis 13 pts (42%) with a planned resection and 8 (30%) considered potentially curative have had surgery, while 3 (1.4%) where treatment was initially considered palliative have had curative-intent surgery. Conclusions: Treatment strategies for pts with mCRC differ significantly based on the treatment intent, and may be affected by surgical preference and referral pattern. Bevacizumab was less likely to be used for already-resected pts and the use of single agent therapy in this group was also not uncommon. Many pts initially considered resectable do not ultimately undergo resection, whereas occasional ‘palliative’ pts may become resectable, confirming the importance of continued consideration of this option.

665 Background: Clinical trials support the addition of bevacizumab (Bev) to first line chemotherapy for metastatic colorectal cancer (mCRC). However, given that there are alternate biological agents that can be used with chemotherapy; and rare but potentially serious toxicities with Bev, there has been variable use of the drug in routine care. The purpose of this study was to prospectively explore 1st line use of Bev in routine clinical care. Methods: A multi-site data collection was initiated in July 2009 when Bev became publicly available in Australia. A particular focus was capturing information regarding clinician decision-making that is not routinely recorded or is often poorly documented. Comprehensive comorbidity data was collected, along with specific factors, both patient (pt) and disease-related, that may impact on treatment decisions. Major adverse events that may be related to Bev were also recorded. Results: For the 2-year period from July 2009-June 2011, a database search identified 278 pts diagnosed with mCRC at five participating hospitals. 240 pts (86%) had received 1st line chemotherapy. 102 (43%) also received Bev, the majority in combination with oxaliplatin based chemotherapy (n = 81, 79%). Bev use increased significantly from 40.4% (34/84) of all pts receiving chemotherapy in July-December 2009, to 65.8% (25/38) in January-June 2011 (p=0.0114). Overall the most frequent reasons for clinicians advising against the use of Bev were a bleeding or asymptomatic primary in situ (n=28, 23%), known hypertension (n=14, 11%), clinical trial participation (n=14, 11%), poor performance status (n=9, 7%), and perceived risk of arterial ischemic event (n=8, 6.5%). There have been four episodes of gastro-intestinal perforation, 3 in pts receiving Bev (2.9% of Bev treated patients). Conclusions: Bev use in first line mCRC has significantly increased over time, presumably as further positive safety data emerges regarding safety in older and frailer pts, and clinician prescribing experience increases. The major grounds for not using Bev in the 1st line mCRC setting were specific clinical contexts where the risk of adverse events may be increased.