ASCO Guidelines Research Articles

Faster ways of pursuing quality control using EHR (Electronic Health Record).

169 Background: In this era of electronic health records (EHR), quality monitoring can be a fast repetitive process. Having access to the relational database of the EHR permits rapid case identification and quality indicator determination. We hereby describe evaluation of hepatitis B testing prior to rituximab administration, a quality measure as per ASCO guidelines. Methods: We connected SQL Query Manager with EPIC Clarity database. Using the object model for medication orders, location and department, we used SQL language to build a temporary dataset of all patients who have a completed order for a Rituximab infusion at a specific department location within the past 6 months. Using the dataset obtained in step 2, we created a smaller dataset with one row for each patient. We updated each unique patient row by updating columns for the count of completed Rituximab infusions, the first infusion date and the last infusion date. We then updated each row from a query of the order procedure and results object model. The unique patient id and component id are the key fields for this query. The Hepatitis B surface antigen and core antibody results were queried from up to 6 months prior to the initial rituximab dose. We looped through the dataset and compared the first Rituximab start date with the Hepatitis B testing date. If the testing date is before the drug administration date, a Boolean column was updated to indicate a 1 for passing the quality measure and a 0 for not passing. Finally, we reviewed that chart of any patients who fail the electronic quality measure check as some Hepatitis B testing may be represented in scanned results and these scanned results cannot be queried. Results: When the final SQL query runs, it takes less than a minute to see the result set. The query can be run at any interval or date range. Once the SQL procedure is created, there is essentially no labor and very low costs to run procedure at specific time intervals. Conclusions: Quality control is integral for improvement in patient care. Doing quality monitoring can be labor intensive, expensive, repetitive and time consuming. By using the relational database created and maintained by the EHR we can accomplish the quality control in faster way that is time and cost effective.

Cancer care decision support for WBC growth-factors (GF): Geographic differences in utilization and provider malleability.

128 Background: Growth factor use is the largest single category of drug expenditure for US cancer patients. Oncology Analytics is a decision support company that assists physicians in determining the appropriate use of GF based on the NCCN, ASCO, and ASH guidelines and the level one data that underlies these guidelines. We hypothesized that there would be geographic variation among GF preference and in the malleability of those practice patterns after OA entered a market. We determined the proportion of initial pegfilgrastim requests for preauthorization over other types of GF as well as the review outcomes and final drug of choice after OA intervention of inappropriate GF requests across three specific jurisdictions: Florida, Puerto Rico, Georgia and Texas. Methods: We analyzed data from drug preauthorization requests for febrile neutropenia prophylaxis submitted by providers in these four states from 10/01/2013 through 09/30/2015. We tested geographic differences in the preference for pegfilgrastim over other GFs; and in review outcomes and final GF of choice after OA intervention for inappropriate pegfilgrastim requests. Chi-square test and linear regression was employed at 95% CL. Results: Oncologists in PR are among the most evidence-based of all GF users, preferring to order the more cost-effective filgrastim. Our research indicates that, on average, 2-3 doses of filgrastim are given at a total cost of $600 to $900 per cycle, compared to pegfilgrastim at $3,800 per cycle. GA and TX oncologists, on the other hand, chose pegfilgrastim over other GFs more than their colleagues (70% GA vs. 72% TX vs 60% FL vs 33% PR) but reduced their pegfilgrastim preference substantially in the last two years by 11% and 36% respectively (linear trend, p < 0.05). Filgrastim was the most common replacement of pegfilgrastim across all states. Conclusions: There are significant geographic variations in the management of febrile neutropenia. These variations contribute to differences in financial toxicity without clinical benefit. Optimizing growth factor utilization management needs to be focused upon certain locales to be most effective. The impact of GF biosimilars has not yet been evaluated.

Abstract P6-12-01: Attitudes and practice of breast surgeons towards referring young women with breast cancer (YWBC) for fertility preservation (FP)

Abstract Background: Despite ASCO guidelines (2006, 2013) recommending that young cancer patients be offered referral for FP as soon as possible after diagnosis, the literature consistently shows suboptimal referral rates for YWBC. Surgeons are in a unique position to initiate early FP referral. Surgeon & Patient Oncofertility Knowledge Enhancement (SPOKE) is one of 5 components of the pan-Canadian RUBY research program for YWBC. SPOKE aims to improve breast surgeon FP knowledge and referral rates. The lead surgeon from each of the RUBY sites was previously interviewed about FP. The goal of the current survey was to assess the baseline oncofertility attitudes and practice of the non-lead breast surgeons at those sites. Methods: An online survey taking approximately 10 minutes to complete was developed specifically for this study. In February 2015, an email invitation with a hyperlink to the anonymous survey was sent to all 86 surgeons identified by the 23 lead surgeons. Repeated reminders were sent by the research assistant over 3 months and a final request was sent by the PI. Participants received a $25 gift certificate. Results: A total of 55/86 (64%) surgeons with an average of 15 years' surgical practice completed the survey. 53% were male, 56% were under age 50, and 93% worked at a cancer centre or university-affiliated hospital. Thirty respondents (55%) indicated that more than half of their practice was breast cancer. Twenty (36%) never or rarely initiated a fertility discussion, and 23 (42%) never or rarely discussed FP options with their YWBC. Twenty-two respondents (40%) stated it was the duty of the medical oncology rather than the surgical team to initiate fertility discussions. Only a minority were quite or very familiar with egg freezing (n=10, 19%) and embryo freezing (n=11, 20%), while only 7 (13%) felt comfortable discussing egg or embryo freezing with their patients. Twenty-four (44%) did not know a FP centre in their area to which they could refer. Compared to surgeons who assumed responsibility for fertility discussion, surgeons who did not think FP referral was their clinical responsibility were less familiar with egg freezing (21% vs. 63%, p<.001) and embryo freezing (32% vs. 73%, p<.01), and were less likely to know where to send FP referrals (31% vs. 85%, p<.05). The most common patient factors that surgeons stated would deter them from FP referral were: poor prognosis, need to start chemotherapy urgently, and already having children. A quarter of surgeons said they would be less likely to refer a highly anxious YWBC for FP. Conclusions: Many Canadian breast surgeons are unaware of the importance of early FP referral and nearly half surveyed did not consider FP referral to be their mandate. A majority of these surgeons lack sufficient oncofertility knowledge to feel comfortable mentioning FP options to their patients, and have not created a protocol for FP referral by the surgical team. In the next phases of the SPOKE study, a knowledge translation intervention will be developed and its effectiveness tested. Support: Canadian Breast Cancer Foundation & Canadian Institute of Health Research (OBW139590). Citation Format: Warner E, Yee S, Glass K, Kennedy E, Foong S, Seminsky M. Attitudes and practice of breast surgeons towards referring young women with breast cancer (YWBC) for fertility preservation (FP). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-12-01.

Abstract P5-12-10: Comparison of the efficacy of tamoxifen and aromatase inhibitors on survival in adjuvant menopausal breast cancer

Abstract Background Meta-analyses of postmenopausal endocrine therapy and recent studies in premenopausal women suggest that aromatase inhibitors (AI) may be superior to tamoxifen (T) in preventing recurrence in early hormone receptor positive (HR+) breast cancer (BC), although there are recent concerns about the impact on overall survival (OS). The BC Cancer Agency adopted ASCO guidelines of an AI as part of adjuvant therapy for menopausal HR+ BC in 2003. Using our population based data, we sought to compare the 10 year survival outcomes for patients starting either T or AI following surgery for HR+BC. Methods Histopathologic and demographic data were collected for all menopausal patients referred to the BC Cancer Agency with a T1-2, node negative, HR+, HER2 negative BC diagnosed between 01/2003 and 12/2009. Patients with prior or synchronous contralateral BC were excluded. Data was cross-referenced to the provincial pharmacy database, which tracks hormone therapy. Significant factors affecting survival were identified using Cox proportional hazard model for OS and Fine and Gray's (FG) model for BC specific and Cardiac Specific Survival (CSS) with causes other than event of interest defined as competing. Results We identified a cohort of 3421 cases with median follow up of 7.8 years (y) for T and 7.4 y for AI. Median age was 65y in both groups, and 8.5% received chemotherapy. 47.8% of tumors were T1c and 22.2% were T2; 15.8 % were grade 3. 10 year OS was 84.4% (95% Confidence Intervals [CI] 82.4%, 86.2%) and 82.7% (95% CI 79.4%, 85.6%) for T and AI cohorts, respectively, (p= 0.02). BCSS did not differ between the groups (p=0.54). We categorized causes of death in each cohort as from BC (20.4% T, 20.6% AI), other cancers (25.4% T, 22.1% AI), cardiovascular-related (CVS) (25.8% T, 34.6% AI), thromboembolic (0.3% T, 0.7% AI %) and other (25.4%T, 19.1 % AI). Table 1 shows Univariate (U), multivariable (M), hazard ratios (Hz) and 95% CI. Table 1 OSBCSSCSS UM (KM)UM ( FG)UM Hz Hz HzTumour Size, continuous<0.0001<0.0001<0.0001<0.0001<0.00010.0280 1.282 (1.142,1.438) 1.882 (0.631,2.090) 1.272 (1.026, 1.577)Age at dx,continuous<0.0001<0.00010.00190.2637<0.0001<0.0001 1.094 (1.080,1.108) 1.016 (0.988,1.044) 1.152 (1.122,1.183)Grade , 3 vs 1<0.00010.0557<0.00010.00180.29930.8719 1.341 (0.993,1.811) 2.973 (1.501,5.889) 1.051 (0.576,1.915)LVI, Yes vs No0.00040.0465<0.00010.00010.24870.0671 1.357 (1.005,1.833) 2.732 (1.637,4.558) 0.474, (0.213,1.054)Chemo use, Yes or No0.0990.21220.05350.50290.02050.8710 0.748 (0.474,1.180) 1.284 (0.618,2.670) 1.128 (0.264,4.824)AI vs T0.020.29270.59250.25540.00410.0123 1.124 (1.142,1.438) 0.742 (0.443,1.241) 1.658 (1.116,2.463) Conclusion While trials show that AIs improve relapse free survival after menopausal HR+BC, their impact on BCSS has been minimal. By contrast they may contribute to CVS deaths, as suggested by our data. We plan to explore this observation further by examining baseline cardiac risk factors within our T and AI cohorts, and by exploring OS, BCSS, and CSS among patients switching to AI after starting T, to identify the optimal adjuvant hormone therapy strategy for menopausal women with HR+ early BC. Citation Format: Chay WY, Speers C, Gondara L, Tyldesley S, Ellard SL, Lohrisch CA, Gelmon KA. Comparison of the efficacy of tamoxifen and aromatase inhibitors on survival in adjuvant menopausal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-10.

An audit of frontline (F)ISH testing outside the Australian setting on HER2 positivity rates in breast cancer and the impact of the 2013 ASCO guidelines

Aim: To determine our HER2 positivity rates for invasive breast carcinoma using frontline FISH testing rather than CISH or SISH in a laboratory outside Australia, and to understand the impact of the 2013 ASCO guidelines on overall HER2 positivity rates.Data: The HER2 status in patients diagnosed with invasive breast carcinoma between 2009–2014 was determined on core or excision specimens sent to Canterbury Health Laboratories (n=797).Results: HER2 positivity rates varied from 12–21%, with an average of 15.5%. With the introduction of frontline FISH testing, the overall HER2 positivity rate was 13%, below the average for the preceding 4 years of 16%, achieving similar rates for positivity as Bilous et al.1 The 2013 ASCO guidelines resulted in an increase in overall Her2 positivity rates to 20.93%.Discussion: Discussion points will include:•Should New Zealand laboratories adopt the frontline ISH testing model as per College guidelines?•Does frontline ISH testing save money from a whole of systems perspective?•The impact of ASCO guidelines on HER2 positivity rates in breast cancer.•Is it time to change the testing algorithm to an ISH only model?•Suggested guidelines for dealing with equivocal FISH results.•Treatment implications for ISH negative, IHC positive results.•Interesting cases of IHC and FISH discordance.Reference1.Bilous M, Morey AL, Armes JE, et al. Assessing HER2 amplification in breast cancer: findings from the Australian In Situ Hybridisation Program. Breast Cancer Res Treat 2012; 134: 617–24. Aim: To determine our HER2 positivity rates for invasive breast carcinoma using frontline FISH testing rather than CISH or SISH in a laboratory outside Australia, and to understand the impact of the 2013 ASCO guidelines on overall HER2 positivity rates. Data: The HER2 status in patients diagnosed with invasive breast carcinoma between 2009–2014 was determined on core or excision specimens sent to Canterbury Health Laboratories (n=797). Results: HER2 positivity rates varied from 12–21%, with an average of 15.5%. With the introduction of frontline FISH testing, the overall HER2 positivity rate was 13%, below the average for the preceding 4 years of 16%, achieving similar rates for positivity as Bilous et al.1 The 2013 ASCO guidelines resulted in an increase in overall Her2 positivity rates to 20.93%. Discussion: Discussion points will include:•Should New Zealand laboratories adopt the frontline ISH testing model as per College guidelines?•Does frontline ISH testing save money from a whole of systems perspective?•The impact of ASCO guidelines on HER2 positivity rates in breast cancer.•Is it time to change the testing algorithm to an ISH only model?•Suggested guidelines for dealing with equivocal FISH results.•Treatment implications for ISH negative, IHC positive results.•Interesting cases of IHC and FISH discordance. Reference1.Bilous M, Morey AL, Armes JE, et al. Assessing HER2 amplification in breast cancer: findings from the Australian In Situ Hybridisation Program. Breast Cancer Res Treat 2012; 134: 617–24.

Thromboembolism incidence in patients with gastrointestinal tract cancer receiving chemotherapy: A single-institutional retrospective cohort analysis.

541 Background: Although cancer and its treatments are well-recognized risk factors for thromboembolism (TE), such as venous and pulmonary TE, there are very few data of the incidence of cancer associated TE in the Asian population. So we conducted a retrospective cohort study to investigate the TE incidence of gastrointestinal tract cancer (GTC) patients (pts) receiving chemotherapy in a Japanese community hospital’s daily practice setting. Methods: All the patients received chemotherapy for GTC in our hospital from January 2008 to May 2015 were identified through medical records review extracted by our hospital data warehouse. We analyzed the incidences of TE by reviewing all the reports of contrast-enhanced computed tomography performed on each patient during chemotherapy and identified the association between several clinicopathological factors and TE incidence using chi-square tests and logistic regression. Results: Five hundred fourteen Japanese GTC pts were analyzed on this study. Patient characteristics were as follows; male/female 317/197, median age 69.1 (range 21.1 - 89.1), Gastric (GC)/Colorectal cancer (CRC) pts 213/301, non-adjuvant (non-Adj)/adjuvant (Adj) setting 314/200, tumor-bearing (TB)/non-TB pts 344/170, multiple primary (MP)/single primary (SP) pts 29/485. The incident rate with TE in GC and CRC pts was 10.3 % (n = 22) and 16.6 % (n = 50), respectively. In relation to the status of malignancy, the incidence of TE was 16.6 % (n = 52) and 10.0 % (n = 20) in non-Adj and Adj setting (p = 0.0367), 16.9 % (n = 59) and 7.9 % (n = 13) in TB and non-TB pts (p = 0.007), 31.0 % (n = 9) and 13.0 % (n = 63) in MP and SP pts (p = 0.007), respectively. Conclusions: We found that there were significantly higher incidences of TE in non-Adj, TB, and MP compared with Adj, non-TB, and SP pts, respectively. Although the ethnic differences of the TE incidence rate between Caucasian and Asian population were reported, the incidence of Asian population received cancer chemotherapy remains unclear yet. So further accumulation of data are necessary to establish a Guideline for Asian to prevent and manage TE occurred during cancer chemotherapy such as ESMO or ASCO guidelines. Clinical trial information: UMIN000018912.

KRAS testing disparities in the state of New Mexico.

551 Background: ASCO guidelines published in 2009 recommend all patients with metastatic colorectal cancer (CRC) receive KRAS testing to guide anti-EGFR monoclonal antibody treatment. Recent literature examining nation-wide trends via the Surveillance, Epidemiology, and End Results (SEER) database showed New Mexico to exhibit the highest KRAS rates of testing out of 18 registries. We aim to explore disparities in KRAS testing in the state of New Mexico. Methods: The New Mexico Tumor Registry (NMTR), a population-based cancer registry participating in the SEER Program, was queried to identify all incident cases of CRC among New Mexico residents from 2010 to 2013. Chi-square tests were used to identify disparity in KRAS testing with a p-value ≤ 0.05 considered significant. Results: A total of 637 patients were diagnosed with metastatic CRC from 2010-2013. As expected, KRAS testing in Stage 4 patients presented the highest frequency (38.4%), though testing in stage 3 (8.5%), stage 2 (3.4%) and stage 1 (1.2%) was also seen. In those with metastatic disease, younger patients (ages 22-39 and 40-64 years) were more likely to receive testing than patients 65 years and older (p < 0.0001). Patients living in or near a metropolitan center received KRAS testing more often than patients living in non-metro and rural areas (p = 0.016). There were no disparities in testing between male and female patients (39.1 v. 37.7%; p = 0.71) or amongst the predominant ethnic groups (p = 0.66). A small increase in the occurrence of KRAS testing was noted from 2010 to 2013 (34.2 to 42.2%); this trend approached though did not obtain significance (p = 0.07). In stage 4 patients, there were no significant differences in rates of wild-type versus mutant status when examined by age (p = 0.95), sex (p = 0.41), ethnicity (p = 0.41), by progressive years (p = 0.42) or geography (p = 0.35). Conclusions: New Mexico exhibits high rates of KRAS biomarker testing in patients with metastatic CRC. Age and geographic disparities exist in the rates of testing, while sex, ethnicity and the year tested showed no differences. Further study is required to explore the reasons for this disparity in KRAS testing, as well as to determine the motivation for testing in stage 1 through 3 CRC which is contrary to current treatment guidelines.

Systematic development of a a breast cancer survivorship program at a small independent oncology practice.

52 Background: It is widely accepted that providing survivorship care plans leads to improvements in outcomes for cancer survivors. Treatment summaries are now part of ASCO and NCCN survivorship guidelines. We faced a unique challenge of implementing the survivorship care plan at the Jones Clinic as a small independent practice. The Jones Clinic consists of three full time physicians and two full time nurse practitioners. We see approximately 850 new patients per year. Methods: As a part of ASCO’s quality training program, we focused on the stage I – III (early stage) breast cancer patients who completed their initial therapy. We formed a team, identified the barriers, created a flow diagram of the process, assigned roles for each individual member and finally implemented the process. Results: The major issues identified were lack of provision in the electronic medical record (EMR) system for survivorship and lack of standardized data entry process. We created a system in the EMR for survivorship data entry and extraction of such data in a document. Since July 2015, one hundred percent of breast cancer patients completing adjuvant therapy at the Jones Clinic have received a survivorship treatment summary and a plan of care. The care plan is also shared with their primary care provider. Importantly, creating a survivorship document required less than 10 minutes of the provider’s time. Conclusions: We are now able to provide our patients with a survivorship care plan and address survivorship issues within thirty days of completion of therapy. Creating the care plan requires minimal time from the providers. Our new process meets ASCO guidelines for survivorship care plans and no additional staffing was needed. We now plan to provide a survivorship care plan to all oncology patients treated with curative intent.

Antiemetics: American Society of Clinical Oncology Focused Guideline Update.

To update a key recommendation of the American Society of Clinical Oncology antiemetic guideline. This update addresses the use of the oral combination of netupitant (a neurokinin 1 [NK1] receptor antagonist) and palonosetron (a 5-hydroxytryptamine-3 [5-HT3] receptor antagonist) for the prevention of acute and delayed nausea and vomiting in patients receiving chemotherapy. An update committee conducted a targeted systematic literature review and identified two phase III clinical trials and a randomized phase II dose-ranging study. In one phase III trial, the oral combination of netupitant and palonosetron was associated with higher complete response rates (no emesis and no rescue medications) compared with palonosetron alone in patients treated with anthracycline plus cyclophosphamide chemotherapy (74% v 67% overall; P = .001). In another phase III trial, the oral combination of netupitant and palonosetron was safe and effective across multiple cycles of moderately or highly emetogenic chemotherapies. In the phase II dose-ranging study, each dose of netupitant (coadministered with palonosetron 0.50 mg) produced higher complete response rates than palonosetron alone among patients receiving cisplatin-based chemotherapy. The highest dose of netupitant (ie, 300 mg) was most effective. All patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus cyclophosphamide) should be offered a three-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone. The oral combination of netupitant and palonosetron plus dexamethasone is an additional treatment option in this setting. The remaining recommendations from the 2011 ASCO guideline are unchanged pending a full update. Additional information is available at www.asco.org/guidelines/antiemetics and www.asco.org/guidelineswiki.

Variable support for ASCO recommendations for the prevention and treatment of cancer-associated venous thromboembolism

SummaryObjectives: To determine the attitude of physicians towards the ASCO evidence-based clinical practice guidelines for venous thromboembolism (VTE) prophylaxis and treatment in patients with cancer.Methods: The ASCO guideline was published in Jan. 2015. Two specialists in in the field assembled a list of arguments for and against each of the ASCO recommendations. ASCO recommendations and pro & con arguments were presented to physicians attending 3 educational seminars on hemostasis in cancer patients. After the presentation each attendee was asked to fill out a questionnaire on how much he agreed with the recommendations and the pro & con arguments.Results: A total of 89 physicians attended the three meetings. 56 questionnaires were returned. The ASCO recommendation with the highest degree of support was that patients undergoing major cancer surgery should receive prophylaxis for 7–10 days and for four weeks after major abdominal or pelvic surgery with high-risk features (84 % Pro). The recommendation with the lowest degree of support was that anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications (56 % Pro = indifference). Arguments based on A) the scientific evidence underlying each recommendation, B) on clinical practicability and patients’ preferences/adherence, C) on the desire to avoid toxicity, malpractice litigation, and cost concerns, ranked equally.Conclusion: The degree of support for ASCO guideline recommendations on prophylaxis and treatment of VTE in cancer is variable. For some key recommendations it is close to indifference. Scientific evidence for a recommendation is just one decision factor among others. Our study underscores the need to further promote educational activities on VTE prophylaxis and treatment in cancer patients particularly among all physicians caring for cancer patients.

Phase III study of APF530 versus ondansetron with a neurokinin 1 antagonist + corticosteroid in preventing highly emetogenic chemotherapy-induced nausea and vomiting: MAGIC trial.

68 Background: Managing chemotherapy-induced nausea and vomiting (CINV) associated with delayed ( > 24-120 h) highly emetogenic chemotherapy (HEC) is an unmet need. APF530, extended-release granisetron, provides sustained release over ≥ 5 days to prevent acute (0-24 h) and delayed CINV. This trial compared the efficacy and safety of APF530 in preventing CINV after HEC in a 3-drug regimen vs a standard 3-drug regimen with ondansetron (Ond). Methods: In this double-blind, multicenter study (NCT02106494), patients (pts) receiving single-day HEC (2011 ASCO guidelines) were randomized 1:1 to APF530 500 mg SC (10 mg granisetron) or Ond 0.15 mg/kg IV and stratified by cisplatin ( ≥ 50 mg/m2, yes/no). Pts were scheduled to receive concomitant dexamethasone (Dex) 12 mg IV + fosaprepitant (Fos) 150 mg IV on day 1 + PO Dex on days 2-4. The primary end point was delayed-phase complete response (CR) (no emesis, no rescue medication). Secondary end points included CR in acute and overall phases and complete control (CC; CR and no more than mild nausea) in acute, delayed, and overall phases. Treatment (tx) comparisons used chi-square test controlling for cisplatin. Adverse events (AEs) and injection-site reactions (ISRs) were assessed. Results: Modified intent-to-treat analysis included 902 pts (APF530, n = 450; Ond, n = 452) with baseline demographics balanced between tx groups. A significantly higher % of APF530 (65%) vs Ond (57%) pts had delayed-phase CR (P= .014). A significantly higher % of APF530 (61%) vs Ond (53%) pts had delayed-phase CC (P= .022, Table). CR and CC rates in acute and overall phases were numerically higher with APF530 vs Ond, but not statistically significant. APF530 was well tolerated. Most common AEs were ISRs, mostly mild or moderate. Conclusions: APF530 with Fos+Dex led to statistically higher CR and CC rates in delayed-phase CINV with HEC vs a standard 3-drug regimen of Ond with Fos+Dex. Clinical trial information: NCT02106494. [Table: see text]

Will breast cancer survivors receive the same content and assessment in survivorship care plans at non-COC sites?

e20634 Background: The Commission on Cancer (COC) standard 3.3 requires survivorship care plans (SCP) in pilot for 10% of patients completing curative intent treatment, with a tiered requirement for implementation to 100% of survivorship by 01/01/2019. In preparation for a workshop on breast cancer (BC) survivorship care, we analyzed the content and assessments in existing and planned survivorship care plans and programs. Funded by Susan G. Komen. Methods: Web survey conducted with 30 hospitals that provide BC treatment and have registered for a BC survivorship care workshop. Using guidelines / recommendations for survivorship care (ASCO, COC, NCCN, NAPBC), we developed a pre-workshop survey on current and planned content and assessments. Results analyzed by simple frequencies and Fisher's exact test. Results: Response rate: 97% (29/30 sites). All sites plan to provide survivorship care for indicated BC patients. Currently, 22% (5/22) of COC sites and 0% of non-COC sites provide BC survivorship plans. Treatment plan summaries are provided to patients by 27% (6/22) of COC sites and 0% of non-COC sites. The table indicates inclusion or plan for specific survivor care plan content and assessments. Conclusions: While all sites have or plan to have SCPs, not all sites plan to include the content and assessments indicated in ASCO and NCCN survivorship guidelines. We found significant difference between COC accredited sites and non-accredited sites in four areas (see table*). Findings indicate the need for technical support and education on how to incorporate guideline suggested content and assessments for SCPs into practice. SCP Content / Assessment COC sites % Non-COC sites % p-value *BC treatment summary 100 43 0.002 *Current disease status, late- and long-term effects 91 43 0.02 *Surveillance and monitoring activities 91 29 0.003 Anxiety / distress / depression 86 57 ns (not significant) *Summary of current medications 82 29 0.02 Cognitive function 77 57 ns Fatigue 77 43 ns Functional / performance status, areas of patient concern 73 29 ns Pain 73 43 ns Patient lifestyle and behaviors 68 57 ns Description of co-morbidities 68 29 ns Immunization and infections 64 43 ns Sexual function 64 43 ns Sleep disorder 64 43 ns

Pharmacist collaborative practice agreement for the management of anemia in malignant disease with erythropoiesis-stimulating agents.

Erythropoiesis-stimulating agents (ESAs) reduce transfusions and increase hemoglobin levels in patients with anemia of malignant disease. A medication guideline and pharmacist collaborative practice agreement (CPA) were developed and implemented to standardize ESA prescribing workflow. The use of ESAs in malignant diseases, in accordance with institutional guidelines, was evaluated to ensure safe and effacious use. An observational study was conducted on all ESA doses given throughout a health system's cancer clinics prior to and after implementation of an ESA guideline and pharmacist CPA. The primary outcome measured was ESA therapy initiated in accordance with guidelines before and after the intervention. Secondary outcomes evaluated were nurse and pharmacist satisfaction, vitals recorded prior to dose, and transfusion rates in patients receiving ESA therapy before and after the intervention. In the pre-implementation group, criteria for initiation were not met by any of the 39 patients; prior to therapy, 5.1 % of patients had not had hemoglobin drawn, 23 % of patients had no iron studies completed, and 29.4 % of myelodysplastic syndrome (MDS) patients had no erythropoietin levels drawn. In the post-implementation group, prior to therapy, all patients had hemoglobin levels drawn, 16.67 % did not have iron studies completed, and all MDS patients had erythropoietin levels drawn appropriately. Chemotherapy-induced anemia (CIA) patients in the pre-implementation group had 71.4 % compliance with receiving chemotherapy within 8 weeks of ESA dose, and the post-implementation group had 100 % compliance. An ESA guideline and pharmacist CPA aligned prescribing practices with the NCCN and ASCO guidelines and improved staff satisfaction.

P097. Intra-operative assessment of excision margins in breast conserving surgery for breast cancer using ClearEdge imaging device

Background: Axillary management in breast cancer is evolving. Recent ACSO guidelines have suggested that axillary node clearances (ANC) are not necessary in the positive axilla in early breast cancers with small nodal burdens, undergoing breast conserving surgery (BCT). According to ASCO guidelines, G1-2, T1-2 tumours with 1 or 2 SLN macrometastases, undergoing BCT should not undergo ANC. We compare current practice in a screening population against these guidelines. Methods: We retrospectively analysed all patients with invasive breast cancer under the regional screening programme (2011e2014), looking specifically at management of patients who would not be offered ANC under ASCO guidelines. Results: 687 screening patients were diagnosed in the time frame. 516 had normal axillary USS and 143 e abnormal. Of the 516 normal USS, 79 (15.3%) had malignant sentinel lymph nodes (SLNB), (45 (57%) were macrometastases of which, 93% had 1e2 positive nodes. 34 (43%) were micrometastases). 86 abnormal USS had SLNB, 16 of which were malignant, 12 macrometastases (100% 1e2 positive nodes). 36 of the malignantmacrometastatic SLNBmet ASCO guidelines. 24 of those received ANC (67%), 7 (30%) of which were positive, 2 with heavy nodal burdens (10/14 and 5/20). The remainder had 1 positive node. Conclusion: Under updated ASCO guidance on SLNB in early breast cancer, we are over-treating the majority of screening patients. However, had these guidelines been followed, 19% of our patients would have had a missed diagnosis of further axillary disease, and in 5% a significant nodal burden would have remained undetected. As clinicians, there is a responsibility to balance and articulate that trade off when discussing axillary management with patients.

P096. Would application of ASCO guidelines on the axilla in early breast cancer result in under-detection in the UK? A retrospective review

P096. Would application of ASCO guidelines on the axilla in early breast cancer result in under-detection in the UK? A retrospective review

Abstract P2-01-14: Pre-operative axillary staging results in over-treatment in some breast cancer patients

Abstract Introduction Following a diagnosis of breast cancer, pre-operative ultrasound staging of the axilla is recommended. Patients found to have metastatic disease on biopsy or FNA can proceed directly to axillary clearance (ALNC) at the time of their breast tumour excision. However, although ultrasound staging is a sensitive test to detect axillary disease, it does not differentiate between low and high volume nodal metastasis. Recent evidence suggests that, in selected patients with low volume axillary disease following SLNB, completion ALNC may be safely omitted. This has been reflected in the recently updated ASCO guidelines. In light of this current trend towards axillary conservation, some patients undergoing ALNC after positive axillary staging may be over-treated. The aims of this study is to establish the nodal burden of patients undergoing ALNC following positive axillary staging and to compare the nodal burden of those patients with those undergoing completion ALNC after a positive SLNB. Methods Data was collected prospectively over 12 months from nine hospitals within the North of England Cancer Network. Age, tumour characteristics, breast operation, axillary staging results, axillary operation(s) and nodal results were recorded. Results A total of 1010 patients with breast cancer underwent pre-operative axillary staging. 215 patients (21%) had an ALNC. Of these, 115 (53%) cases underwent a primary ALNC after positive staging. The remaining 100 (47%) patients had a completion ALNC following a positive SLNB. The nodal burden for patients undergoing ALNC is shown in the table below: Total number of positive nodesALNC after positive stagingALNC after positive SLNB n patients% patientsn patients% patients087001322847472131124243121011114111044≥539341414Totals115 100 Analysis of the data revealed that tumour size was a significant predictor of low volume axillary disease (i.e. <3 nodes positive) [p=0.02, Mann-Whitney test]. Conclusion In this study, 46% of patients undergoing ALNC after positive staging had low volume disease (2 or less positive nodes). In the context of recent evidence if these patients had undergone a SLNB following the positive pre-operative staging they may have avoided a completion ALNC. This study demonstrates tumour size to be a significant predictor of low volume axillary disease and thus may be an important factor to consider alongside pre-operative staging when selecting patients who may be better managed by a SLNB rather than proceeding directly to ALNC. Citation Format: Andrew Pieri, Henry Cain, Sebastian Aspinall. Pre-operative axillary staging results in over-treatment in some breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-14.

A Phase 2 Trial of AZD1152 in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) and has an aggressive natural history. R-CHOP has improved patient (pt) survival and established a standard of first line care. In the rituximab era the prognosis for relapsed DLBCL is poor, with salvage chemotherapy and autologous stem cell transplantation (ASCT) only curing a small proportion (<25% of all relapses) of those with adequate performance status. Relapsed DLBCL in those unfit for ASCT or post-ASCT is rarely curable, and remains an unmet clinical need.AZD1152 (barasertib) is a highly selective and potent Aurora B kinase inhibitor. Aurora B kinase has an important function at the spindle assembly check-point in mitosis. The kinase is overexpressed in 48% of DLBCL. Exposure of high grade lymphoma B cells to AZD1152-HQPA in vitropotently induced growth arrest and apoptosis via caspase-dependent and independent mechanisms.AZD1152 was well tolerated in a phase I study in relapsed/refractory acute myeloid leukaemia. We performed a phase II single arm open-label trial to determine the efficacy and tolerability of AZD1152 in relapsed/refractory DLBCL pts who had failed or were ineligible for salvage/high dose chemotherapy and had received at least one line of potentially curative immunochemotherapy.MethodsPts with relapsed/refractory (de novoor transformed indolent NHL) DLBCL with measurable disease (at least a non-irradiated single lesion (>1.5cm)) were treated with up to six cycles of 96-hour continuous intravenous (iv) infusions of AZD1152 as an inpt every 3 weeks.Due to concerns over possible precipitation of drug in the line, regular 4 hourly saline flushes were required via each lumen to maintain patency. Prophylactic G-CSF was permissible per ASCO guidelines. Ongoing cycles were commenced when neutrophils recovered to ≥1.0x109/L and platelets to ≥50x109/L.The primary endpoint was overall response rate (ORR). Secondary end-points were progression-free survival (PFS) at one year, % change in tumour size, and safety measured by the incidence and severity of adverse events (AEs). Response assessment using FDG-PET was completed at day 15 of cycle 2. Pts with stable disease (SD), minimal, partial (PR) or complete response (CR) according to Cheson criteria remained on protocol, but those with progressive disease (PD) were taken off study.As data that suggests MYC overexpression may enhance responses to aurora B kinase inhibition, MYC by IHC and FISH for c-MYC translocation was performed. All diagnostic specimens were reviewed by specialist haemato-pathologists.ResultsFifteen pts were enrolled in 20 months, and received 1-6 cycles. Overall, 42 cycles were administered (41 at full dose). One pt completed all six planned cycles. The cohort included 8 males and 7 females, with a median age of 65 (35-74 years). 13% had a low International Prognostic Index (IPI) (0-1), 53% an intermediate IPI (2-3) and 33% a high IPI (4-5). The best ORR was 20% (see Fig 1 for tumour percentage reduction) with no cases of CR and 3 PR. 33% obtained SD for between 2-6 cycles. The median PFS was 60 days (95% CI 36-84 days) (see Fig 2). IPI (p=0.584) (See Fig 3), gender (p=0.113), disease bulk at diagnosis (p= 0.654) or c-MYC dysregulation (p=0.331) did not predict PFS. Early discontinuation occurred in 14 pts from PD.SafetyMost AEs were grade 1-2. 18 episodes of neutropenic fever occurred, including one grade 4 bacteraemia. There were no fatal SAEs and each episode resolved with iv antibiotics and G-CSF. All other toxicities were transient, manageable and expected. 13% of pts developed a total of 2 episodes of mucositis following 42 total doses. Neutropenia (grade 3-4), diarrhoea and nausea were common but manageable and expected. No Suspected Unexpected Serious Adverse Reactions occurred.ConclusionsThree-weekly AZD1152 was safely administered to pts with relapsed DLBCL. Responses were seen, providing a proof of concept that Aurora B kinase is a valid target in DLBCL. However, efficacy was modest. The infusate delivery was cumbersome. Dose intensity was maintained during treatment. Important but manageable AEs included neutropenic fever and mucositis. Aurora B kinase is a rational target for further investigation. NCT01354392. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Lenalidomide and Rituximab in Combination As Initial Treatment of Chronic Lymphocytic Leukemia: Initial Results of a Phase II Study

Background.Lenalidomide (Len) is an immunomodulatory drug with single agent activity in patients (pts) with treatment-naïve (TN) CLL, (overall response rate (ORR) 56-65%, Chen JCO 2011, Ferrajoli Blood 2011). Given the encouraging results of the combination of Len and rituximab (R) in relapsed CLL, we explored this combination as initial therapy. TN pts could derive greater benefit than relapsed pts from Len + R given their less compromised immune function.Methods.Fifty-eight pts were enrolled between 01/2012 and the present time. All patients had treatment indications per IWCLL 2008 criteria, WHO performance status ≤2 and adequate hepatic and renal function. Patients with HIV, hepatitis B or C infection were excluded.Treatment consisted of R 375 mg/m2 IV given weekly for 4 weeks then monthly during months (mo) 3-12 and Len 10 mg PO/day from day 9 for 24 mo. Allopurinol 300 mg PO daily was given for the first 2 weeks. No pts received antibiotic or DVT prophylaxis. Use of growth factors was allowed according to ASCO guidelines. Responses were assessed (2008 IWG criteria) at mo 3, 6 and every 6mo thereafter.Results.Forty-eight patients are evaluable for response and toxicity (8 too early, 1 lost to follow-up and 1 diagnosed with metastatic colonic adenocarcinoma within 1 week of study entry). Median age was 66 yrs (42-79). 29 (59%) pts were ≥age 65. 22 pts (46%) had Rai stage III-IV disease. Median β2M level was 3.8 mg/dL (1.4-10.5). 24/37 pts (65%) had unmutated IGHV gene and 31 pts (65%) expressed ZAP-70. 4 pts (8%) had del(17p) and 15 pts (32%) del(11q).Forty pts responded (ORR 83%). 7 pts (14.6%) achieved CR (1 MRD negative) and 33 (68.8%) achieved PR (including 7 nodular PRs). Median time to CR was 11mo (range 5-27). 5 pts discontinued therapy before the 3mo evaluation (4 due to toxicity and 1 due to unrelated co-morbidities). Six pts discontinued between 3 and 6mo (4 for refractory disease and 2 for toxicity after achieving PR). ORR was similar for patients with mutated and unmutated IGHV gene (85 vs 83%, p=0.96), age ≥65 and <65 (85 v 82%, p=0.8) and those with β2M <4.0 vs ≥4.0 (89 vs 75%, p=0.19). No difference in ORR was observed according to FISH; 3 of 4 pts (75%) with del(17p),11/15 (73%) with del(11q) and 25/28 (89%) of pts with other FISH characteristcs responded, p=0.38. There was a trend toward inferior ORR for patients with complex metaphase cytogenetics (≥3 distinct abnormalities) compared to pts without (2/6 = 33% v 88%, p=0.052). Given the small number of events, subgroup analysis could not be performed for time to treatment failure (TTF) and survival endpoints.47 pts are alive; one died from pneumonia 3mo after treatment discontinuation. Median TTF and survival have not been reached in evaluable pts at a median follow up of 11mo (range 3-30). (figure) [Display omitted] The most common treatment-related hematological adverse event was neutropenia [grade (G) 3 in 11 pts (23%) and G4 in 13 (27%)]. G3 thrombocytopenia occurred in 6 pts (13%) and G3 anemia in 4 pts (8%). G3-4 infectious episodes occurred in 5 pts (10%) and other G3 non-hematologic toxicities were uncommon (tumor lysis syndrome, pulmonary embolism (PE), rash and rituximab infusion reaction were each experienced by 1 pt). Ten pts discontinued therapy due to toxicities: persistent G2 rash in 4 pts, G2 DVT in 2 pts, G3 neutropenia in 2 pts and G3 PE, G2 recurrent infections and G2 fatigue in 1 pt, respectively). Pts ceasing therapy due to toxicity received a median of 4 courses of treatment (range 2-18). Median time to progression or next treatment after cessation of Len+R was 2.8mo (0-14).Median baseline IgG was 654mg/dL (range 216-1510). There was no significant change in IgG from baseline to 6 or 12mo and a trend toward an increased IgG at 24mo, median %change 13.5%, p=0.062.Conclusions.Len + R achieves high ORR, comparing favorably with our historical Len monotherapy cohort. Similar efficacy was seen in older pts and in pts with unfavorable baseline characteristics, with the potential exception of patients with complex cytogenetics. Treatment was equally well tolerated in younger and older pts. Myelosuppression was frequently observed, but serious infections were uncommon. An increase in IgG levels was observed in pts undergoing Len monotherapy following completion of rituximab infusions. DisclosuresOff Label Use: Use of lenalidomide in CLL. Keating:Celgene: Consultancy; Roche: Consultancy. Wierda:Celgene: Consultancy; Roche: Consultancy. Ferrajoli:Celgene: Research Funding.

Quality of febrile neutropenia management in a regional cancer center emergency department.

104 Background: ASCO's current guidelines for febrile neutropenia (FN) management support antibiotic administration within one hour of presentation to the emergency department (ED). Prompt initiation of antibiotic therapy is vital to decrease the likelihood of adverse outcomes. Many studies, however, have reported significant delays in antibiotic initiation with mean wait times far exceeding ASCO's guidelines. We aimed to assess the quality of FN management at a regional cancer centre ED. Methods: Patients undergoing chemotherapy who visited the ED at the Peel Regional Cancer Center in Ontario, Canada between 04/12 - 03/13 were identified using electronic medical records. Patients were excluded if there was no record of chemotherapy delivery within 30 days prior to ED visit. ICD-10 codes and chart data were used to identify patients who had presented for either fever or infection. The primary outcome measures were three major quality of health indicators; time to assessment by a physician, Canadian Triage and Acuity Scale (CTAS) score, and time to initiation of intravenous antibiotics. Results: In total 239 records were included in the analysis. CTAS score was concordant with recommendation for FN (level 1-2) in 85% of patients and did not vary based on primary cancer site (p = 0.17). The mean time to physician assessment was 97.2 min and the mean time to initiation of IV antibiotics was 194.7 min. Overall, 14.6% of patients received their first dose of antibiotic therapy within the recommended 1 hour window. Conclusions: Our audit identified a large margin for improvement in the time to initiation of antibiotic therapy for chemotherapy patients with suspected FN. Prompt recognition and initiation of standardized treatment pathways for FN in the ED may improve the time to initiation of antibiotic therapy. In an attempt to address this gap in quality we have developed and distributed a standardized wallet-sized fever card to all patients receiving cytotoxic chemotherapy within our regional cancer program. This card contains information pertaining to the current chemotherapy treatment and recommended ED treatment protocols for FN. An evaluation of the impact of these cards is ongoing.

Myeloid growth factor utilization in a commercial and Medicare population: Phase 1 of a quality improvement initiative.

242 Background: Some clinical practice guidelines encourage the judicial use of myeloid growth factors (MGFs) in the prevention of chemotherapy-induced febrile neutropenia (FN) because of efficacy and safety concerns. For example, the ASCO guidelines state that a dose reduction of myelosuppressive chemotherapy in patients with incurable disease rather than prescribing a MGF for secondary prophylaxis is a reasonable alternative. Because there is wide variation in MGF prescribing, New Century Health (NCH) conducted a quality improvement analysis of MGF requests in a commercial and Medicare population. The objectives are to: (1) describe the cohort demographics, (2) identify areas of improvement to promote cost-effective use, and (3) measure the economic impact from interventions. Methods: MGF authorization requests for oncology indications to NCH in 2013 were analyzed for cohort demographics: age, weight, tumor diagnosis, and treatment intention (e.g., metastatic/palliative, curative, etc.). Requests were analyzed for concurrent use with chemotherapy, approval status of the request (including reason for withdrawal), and cost saving associated with interventions. Results: There were 7,958 requests for a MGF; 81% were for pegfilgrastim and 19% for filgrastim. Average age of the cohort was 66 years, weight-based dosing (&gt;70 kg) was appropriate in 43% of patients receiving 300 mcg and 72% of patients receiving 480 mcg. MGFs were most commonly requested in: breast (18%), lung (17%), lymphoma (14%), and gynecologic (8%) tumors. 40% of requests were for metastatic/recurrent disease and 38% for curative intent. 6,724 (84%) of requests were authorized based on established-use criteria. The main reason for not authorizing was lack of compendia support for both primary and secondary prophylaxis; this resulted in approximately $3.5 million in cost savings. Conclusions: There is opportunity to improve efficiency of MGFs use in this population through a dose rounding protocol and by promoting chemotherapy dose reductions, as advocated by the ASCO guidelines. Further analysis will assess the concordance of MGF use with guidelines, specifically in regard to chemotherapy regimens and their risk of FN.