Rationale for the utilization of biological targeted agents (bTAs) in the treatment of metastatic colorectal cancer (mCRC), single tertiary cancer center experience.

e15589 Background: Worldwide treatment for 1st line (1LTx) mCRC included doublet or triple chemotherapy with or without bTAs. In Quebec, the anti-EGFR therapy (panitumumab or cetuximab) was only recently approved in this setting for patients RAS WT, Bevacizumab (B) not eligible. In this study we evaluated the rational and outcomes using bTAs. Methods: Retrospective study assessing mCRC pts treated with or without bTAs at any time throughout the course of therapy at the Jewish General Hospital between 2010-2018. Pts were divided in 3 groups according to their 1LTx for analysis: Chemotherapy alone (1LChA), Chemotherapy plus B (1LChB), and anti-EGFR with or without chemotherapy (1LaEGFR). The primary objective was to assess the rational of bTAs prescription based in 1LTx selection. Secondary objectives included safety, PFS and OS. Results: Among a total of 463 pts with mCRC; 196 pts (42.3%) received 1LChA, 246 pts (53.2%) 1LChB, and 21 pts (4.5%) 1LaEGFR respectively. 1LChA group, 51% omitted bTAs for physician-patient preferences, 96 pts (49%) had contraindications for B, and 79 pts (40.3%) were potentially candidates for aEGFR, but did not receive it. 152/196 (77.5%) pts continued to 2LTx and 34.8% received bTAs. As for the 3LTx, 78/196 (40%) received a treatment, 48.7% received bTAs. The most common grade 3-4 adverse events (AEs) were hypertension and bowel perforation in B, gastrointestinal (GI) symptoms and skin reaction (SR) in aEGFR. 1LChB group, 31 pts (12.6%) presented AEs related to B. 191/246 pts (77.6%) continued to 2LTx with 48 pts (25%) receiving ChB despite progression in 1LTx on this bTA and 19 pts (10%) receiving aEGFR. The most common AEs reported in 2LTx were GI symptoms and neuropathy. In 3LTx, 54/91pts (59.3%) received aEGFR therapy and 8 pts (14.8%) had SR AEs. 46 pts (18.6%) continued to 4LTx, 13/46 pts (28.2%) received aEGFR. 1LaEGFR group, the most common AEs were SR and GI symptoms. 11/21 pts (52.3%) continued to 2LTx; 5 pts (45.4%) switching bTA class and receiving ChB. 81% pts started treatment between 2017-2018 and had at least two contraindication criteria for. The median PFS for the 1LChA and 1LChB groups were 10 and 11.5 months, respectively, and were not statistically significant (p=0.22). The OS with 1LChA and 1LChB was 33.26 vs. 27.80 months (p=0.27). The PFS and OS between 1LChA and 1LaEGFR were 10 vs 11 months (p= 0.27) and 33.26 vs. 35.07 months (p=0.13). Conclusions: The outcome and tolerability of bTAs in mCRC appear similar in our institution and randomised trials. We were not able to detect any significant difference among the three groups of comparison. The 1LaEGFR available data in this subset of patients are limited. Our data highlights the importance of optimal therapeutic sequencing to prolong OS. Dedicated studies are needed in order to determine the best bTAs therapeutic strategy in mCRC.

Women in Medicine: Dr. Lysanne Campeau

Dr. Lysanne Campeau (M.D., C.M., Ph.D., F.R.C.S.C.) is an Assistant Professor of Urology at McGill University’s Jewish General Hospital. Through her flamboyant career in medicine, her research accomplishments and her advocacy work for gender equality in medicine, she is a model of ambition, dedication and passion. Dr. Campeau completed medical school as well as her urology residency at McGill University. She is the first woman to complete her entire residency at McGill University in this specific field. Dr. Campeau then went on to complete a clinical fellowship in Female Pelvic Medicine and Reconstructive Surgery at New York University, as well as a Ph.D. in Physiology and Pharmacology at Wake Forest Institute for Regenerative Medicine. She then came back to work as a urologist at the Jewish General Hospital and a clinical researcher at the Lady Davis Institute. Her research interests lie in female pelvic medicine, voiding dysfunction and urogenital reconstruction. In addition to her clinical and academic duties, Dr. Campeau is involved in teaching urology residents as well as in some volunteer endeavours in the community. A resilient person, Dr. Campeau builds on her experience of gender discrimination in medicine to advocate for equality in her field. She also aims to raise awareness on the topic of incontinence, which is often taboo among the public. Through awareness campaigns as well as her innovative research in the field, Dr. Campeau works to develop new treatments and improve outcomes for patients who suffer from this condition. Dr. Campeau is a positive leader and role model for aspiring female physicians, to whom she advises to cultivate adaptiveness, integrity and honesty in order to navigate the challenging journey that is medicine.

P.032 What do elective students learn about the specialty of Neurology (and what can that teach us)?

Background: “Neurophobia” describes a fear of Neurology on the part of medical students. This contrasts with the “neurophilia” that exists in society with increasing awareness of disorders such as stroke and multiple sclerosis. Ideally, we should take advantage of “neurophilia” to promote our specialty’s strengths. One step would be to better understand what students learn from a Neurology elective. Methods: This was a qualitative study. Students completing an elective between September 2011 and March 2015 at the Jewish General Hospital (JGH) in Montreal completed written pre- and post-elective questionnaires. Results: 36 students participated; 15 from McGill, 11 from other Canadian medical schools, and 10 from International medical schools. Many students changed their opinion about Neurology, with fewer citing lack of treatments or poor patient prognoses as negatives after completing their elective. They valued knowledge acquired about the neurological exam and problem-solving, while the range of cases and subspecialties surprised them. Many would diversify the setting of their elective to better experience this variety. Conclusions: More diversified elective experiences could showcase the strengths of our specialty and the scope of neurological practice. Presenting Neurology as a challenging, intellectually stimulating specialty that emphasizes problem solving could increase student interest.

Treatment sequencing in MPC, insights from a 3˚ care center.

400 Background: Since 2011, options for treatment of metastatic pancreatic cancer (mPC) have improved with the use of nab-paclitaxel plus gemcitabine (n-PGEM) or FOLFIRINOX (FFX) as first line treatments (1LTx). In 2016, Nanoliposomal irinotecan plus 5FU (nal-IRI-5FU) demonstrated efficacy in 2LTx. Yet, optimal sequential Tx has not been established. Methods: We evaluated oncologist-selected Tx algorithms and resultant progression free & overall survival (PFS, OS) for pts with mPC from 2010 and 2018 at the Jewish General Hospital, Montreal, QC. This retrospective study included 203 pts with mPC (33 to 89 years, 54% male). Results: 1LTx included 66 pts on FFX, 60 pts on n-PGEM, and 66 pts on single-agent GEM. The remaining pts received Capecitabine (CAP) or another Tx (N = 11). Mean PFS in FFX, n-PGEM, and GEM groups was 5.07, 5.52, and 4.10 months, respectively (progression was 1˚ or 2˚ disease progression or a change of Tx due to adverse events or intolerance). Only the FFX and GEM groups were significant when compared (p = 0.049). Only 43.8% of pts (N = 89/203) advanced to 2LTx most receiving GEM (N = 27), n-PGEM (N = 21), or FFX (N = 11), PFS 3.87, 7.04, and 2.30 months, respectively. FFX and n-PGEM groups were significant when compared (p=0.011). CAP and nal-IRI-5FU were 2LTx options for 25.8% (N=23/89) and 7.9% (N = 7/89) of pts, respectively. For 30 pts in 3LTx, Txs included: nal-IRI-5FU (N = 8), clinical trials (CT) (N = 7), GEM (N = 5), FFX (N = 4), n-PGEM (N = 2), CAP (N = 2) and Irinotecan (IRI) (N = 2). Only 7 pts received 4LTx: GEM (N = 3), CAP (N = 2), CT (N = 1), and IRI (N = 1). Median OS from start of 1LTx for pts in FFX (N = 60), n-PGEM (N = 41), and GEM (N = 60) groups was 11.42, 9.50, and 6.23 months, respectively. (Excluding pts on ongoing tx and other censored data points). GEM tx was a significant prognostic factor for shorter OS, GEM verus FFX, HR 1.673 (1.165 to 2.402, p = 0.0053), GEM versus n-PGEM, HR 1.511 (1.012 to 2.258, p = 0.0437). No difference in survival was seen between FFX and n-PGEM groups, HR 0.903 (95% CI 0.605-1.349, p = 0.6196). Conclusions: Though FFX and n-PGEM are considered mainstays of 1LTx, GEM was chosen by physicians in ~1/3 of cases despite reduced PFS. Pts on FFX or n-PGEM had better OS compared to GEM alone, as expected. Further investigation into Tx sequencing in this and larger cohorts, is needed.

Shifting Paradigm In Physician Practice Patterns In The Application Of Thromboprophylaxis Guidelines: An Updated Analysis Of Venous Thromboembolism Prevention At a University-Affiliated Tertiary Care Center

Background Venous thromboembolism (VTE) is an important cause of morbidity and mortality in hospitalized patients. Prophylactic antithrombotic therapy has been shown to be the most effective method to reduce the health and economic burden of an often silent disease. The American College of Chest Physicians (ACCP) has been instrumental in developing guidelines for the use of prophylactic antithrombotic therapy. However, several studies have consistently demonstrated underuse of these guidelines. One such study, conducted in 2001 at our university- affiliated hospital (Jewish General Hospital, Montreal, Canada), showed that 17.4% of all VTE cases in hospitalized patients were potentially avoidable (Arnold DM, Kahn SR, et al. Chest2001) and that this represented 2/3 of all VTE cases for which thromboprophylaxis had been indicated. Consequently, in 2005, we implemented an institution-wide thromboprophylaxis policy with the aim of improving VTE prevention. Five years after this change, we reassessed physician practice patterns at our institution with regards to application of thromboprophylaxis guidelines, and determined the avoidability of each case of VTE. Objective To identify and characterize cases of potentially avoidable VTE: cases for which thromboprophylaxis was indicated according to ACCP consensus guidelines for VTE prevention, yet was administered inadequately. Methods We conducted a retrospective cohort study, which included all patients with objectively diagnosed VTE who were admitted in 2010 to the Jewish General Hospital, a university-affiliated tertiary care institution. A standardized case-report form was used to obtain data from patient charts on patient characteristics, risk factors for VTE, risk factors for bleeding, presence of indications for thromboprophylaxis as per ACCP guidelines (e.g. surgery in last 3 months, hospitalization for pneumonia), and thromboprophylaxis regimen received. Each case was classified as avoidable (a case in which thromboprophylaxis was indicated but inadequately administered), non-avoidable (a case in which thromboprophylaxis was indicated and was correctly administered), spontaneous (a case in which a VTE occurred with no evident indications for thromboprophylaxis), and ineligible (a case in which there was either contraindication to thromboprophylaxis, or which occurred at another institution). The proportions with avoidable, non-avoidable and spontaneous VTE were compared to the results we obtained in our 2001 study. Results Of the 230 cases of VTE diagnosed in 219 patients, 55 cases were classified as avoidable (23.9%), 87 were non-avoidable (37.8%), and 74 were spontaneous (32.2%). Therefore, of the 142 (i.e. 55+87) cases for which thromboprophylaxis was indicated, 38.7% were potentially avoidable. Of the avoidable VTE cases, the majority (51.0%) were due to omission of thromboprophylaxis, with another 40.0% due to delay in initiation of thromboprophylaxis. The majority (75%) of avoidable cases occurred during general medical admissions, with a minority occurring in the context of orthopedic surgery. Common additional VTE risk factors in avoidable cases were cancer, obesity and prolonged immobility. Conclusions 1 in 4 cases of all VTE, and 1 in 2.5 cases of VTE for which thromboprophylaxis was indicated could potentially have been avoided had thromboprophylaxis been administered according to ACCP guidelines. The ratio of avoidable to non-avoidable cases (38.7%; 1 in 2.5) has significantly improved since 2001(67.7%; 2 in 3). Physician education and the adoption of an institution-wide protocolized approach to thromboprophylaxis may be largely responsible for this favorable shift. However, there has also been a significant decrease in the number of VTE cases deemed “spontaneous” from 2001 to 2010 (70.8% to 32.2%). During this time period, there were no major guideline changes in indications for VTE prophylaxis that might have led to fewer VTE being labeled spontaneous and more VTE being labeled provoked. The decrease in spontaneous cases of VTE might be ascribable to a change in patient population (e.g. increased numbers of hospitalizations for malignancy-related complications), as well as a shift towards having a lower threshold to identify patients as having risk factors for VTE (e.g. patients with pneumonia, non-fracture injuries). Disclosures: No relevant conflicts of interest to declare.