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Ami M. Vyas, Hilary Aroke and Stephen J. Kogut

Background: We examined guideline-concordant care among women with HER2+ MBC and determined the magnitude of differences in guideline-concordant care between those with positive and negative hormone receptor (HR) status by utilizing a non-linear decomposition technique. Methods: We conducted a retrospective observational cohort study using the Surveillance, Epidemiology, End Results-Medicare linked database. The study cohort consisted of women age >66 years diagnosed with HER2+ MBC in 2010–2013 (N=241). Guideline-concordant initial care within 6 months of cancer diagnosis was defined as per NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). A multivariate logistic regression was performed to identify the significant predictors of guideline-concordant care. A post-regression non-linear decomposition was conducted to examine the magnitude of disparities in guideline concordant care by women’s HR status. Results: 76.8% of the study cohort received guideline-concordant care, while 23.2% did not. As compared to those who did not receive guideline-concordant care, women who received guideline-concordant care were significantly more likely to have positive HR status (adjusted odds ratio (AOR)=2.11; P=.04), had good performance status (AOR=3.46; P=.0008), and had a higher number of oncology visits (AOR=8.05; P<.0001). With 1 year increase in age at cancer diagnosis, there was 5% lesser likelihood of receiving guideline-concordant care (AOR=0.95; P=.04). From the decomposition analysis, 19.0% of the disparity in guideline-concordant care between women with positive and negative HR status was explained by differences in their characteristics. Enabling characteristics (marital status, census-level income, and education) explained the highest (22.8%) proportion of the disparity, followed by external environmental factors (location of residence, SEER region, hospitals offering oncology services) at 5.3%, and need-related factors (tumor grade, comorbidity, performance status, number of metastases) at 3.2%. Conclusion: Almost one quarter of the study cohort did not receive guideline-concordant care. There are opportunities to improve cancer care for women with negative HR status who have lower socioeconomic status. The high unexplained portion of differences in guideline-concordant care (81.0%) can be due to patient preferences for treatment, propensity to seek care, and organizational and physician-level factors not captured in the database.

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Komal Jhaveri and Francisco J. Esteva

patients with metastatic breast cancer (MBC) still develop acquired resistance to trastuzumab, 9 - 12 thereby highlighting a need to develop other effective anti-HER2-directed therapies. 13 Pertuzumab is a humanized, recombinant monoclonal antibody that

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Bianca Lewis, Caitlin R. Meeker, Elizabeth Handorf, Kelly Filchner, Rino Seedor, Jennifer S. Winn, Lori J. Goldstein and Efrat Dotan

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Donna Trauth and Lori J. Goldstein

. 6 Nabholtz JM Gelmon K Bontenbal M . Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer . J Clin Oncol 1996 ; 14 : 1858 – 1867 . 7 Seidman A Hudis CA Albanel J . Dose

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Efrat Dotan, Elizabeth Handorf, Caitlin R. Meeker, Bianca Lewis, Kelly Filchner, Jennifer S. Winn and Lori J. Goldstein

Introduction: Geriatric assessment (GA) is recommended for evaluating an older cancer patient’s fitness for treatment; however, it is underutilized in the community. We sought to define the gaps that exist in community oncology practices in the assessment and management of older MBC patients through implementation and training on the use of GA for the care of older MBC patients. Methods: The first phase evaluated community oncology providers using questionnaires regarding their assessment and management of older MBC patients. The second phase included training through implementation of a patient self-administered GA among patients ≥65-years-old with MBC. The providers were blinded to the results of the GA and provided their assessment. Comparison of the 2 evaluations was conducted. The GA was ultimately shared with the providers, who were questioned about the effect of the results on care recommendations. Results: 43 providers from 10 practices were enrolled. Phase I revealed the majority (77%) of providers recognized the utility of GA, yet only 42% routinely conducted a GA pretreatment. Most providers (77%) reported evaluating various GA domains through patient interview rather than validated assessments. Validated scales were used in low rates to evaluate cognition (23%), psychosocial status (12%), and toxicity risk (9%). The limited use of validated assessment tools was not influenced by the provider’s demographics or their views of GA utility. Eighty patients took part in the training phase of the study to date, with average age 74 (range, 65–90) and 84% Caucasian. The majority of patients had subtype ER/PR+, HER2- (75%) and 46% were on first-line therapy. 277 recommended interventions were identified: 174 immediate interventions and 103 suggested interventions. Following review of these results, providers reported being surprised in 40% of the cases, mainly with lower than expected cognitive or social support scores. The providers reported plans for change in management in 44% of the patients as a result of the GA findings. Conclusion: Despite acknowledgement of the value associated with pretreatment GA, it is rarely used in the community. Furthermore, interview rather than validated assessment tools are used to identify age-related concerns. In our preliminary results, the GA identified a large number of deficient areas that had not been identified through the provider’s assessment, and resulted in management change. Additional updated results will be presented at the conference.

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Sriman Swarup, Anita Sultan, Somedeb Ball, Francis Mogollon-Duffo, Nimesh Adhikari, Yin M. Myat, Myo H. Zaw, Catherine Jones and Kyaw Z. Thein

Background: Breast cancer is the most common cancer in women, and the majority of breast cancers express the estrogen receptor or progesterone receptor. Inhibition of CDK4/6 signaling pathway has shown survival benefit in advanced breast cancer by overcoming endocrine therapy resistance. Yet, there are considerable hematologic toxicities associated with CDK 4/6 inhibitors and hence, we performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk. Methods: MEDLINE, EMBASE databases, and meeting abstracts from inception through September 2018 were queried. RCTs that mention anemia, thrombocytopenia, leukopenia, neutropenia, and neutropenic fever as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) and risk difference (RD) with 95% CI. Random effects model was applied. Results: 8 RCTs (7 phase III and 1 phase II studies) with a total of 4,557 patients were eligible. The study arms used palbociclib/ribociclib/abemaciclib with letrozole or anastrozole or fulvestrant or other hormonal agent while the control arms utilized placebo in combination with letrozole or anastrozole or fulvestrant or other hormonal agent. The RR of all-grade side effects were as follows: anemia, 3.494 (95% CI: 2.535–4.814; P<.0001); thrombocytopenia, 6.066 (95% CI: 3.055–12.046; P<.0001); leukopenia, 10.376(95% CI: 7.236–14.879; P<.0001); and neutropenia, 14.387 (95% CI: 10.877–19.031; P<.0001). The RR of high-grade adverse effects were as follows: anemia, 2.251 (95% CI: 1.393–3.637; P=.001); thrombocytopenia, 3.696 (95% CI: 1.417–9.642; P=.008); leukopenia, 22.083(95% CI: 12.126–40.217; P<.0001); neutropenia, 33.527(95% CI: 17.271–65.082; P<.001). Neutropenic fever was noted in 71 (3.73%) in CDK 4/6 inhibitors group vs 28 (2.18%) in control arm. The pooled RR was statistically significant at 12.056 (95% CI: 1. 352–3.127; P=.001) and RD was 0.014 (95% CI: −0.002–0.029; P=.078) Conclusion: CDK 4/6 inhibitors–based regimen significantly contributed to all hematologic toxicities as well as febrile neutropenia. The improved efficacy outcomes and manageable toxicities with CDK 4/6 inhibitors are observed with proper supportive care and close monitoring.

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Anita Sultan, Sriman Swarup, Somedeb Ball, Miguel Quirch, Meily Arevalo, Yin M. Myat, Ye Aung, Myo H. Zaw and Kyaw Z. Thein

Background: CDK4 and CDK6 are cyclin-dependent kinases that control transition between G1 and S phases of the cell cycle, hence controlling cell cycle progression by reversible combination with cyclin D1. In cancer cell, CDK4/6 activity is overexpressed, which can lead to amplification or overexpression of the genes encoding for CDK 4/6 or the cyclin D. Additionally, loss of endogenous INK4 inhibitors can also lead to over activity of CDK4 and CDK6. We undertook a meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities associated with CDK 4/6 inhibitors. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts from inception through September 2018. In our analysis, we incorporated RCTs that mention GI toxicities and elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) as adverse effects. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Random effects model was applied. Results: A total of 4,557 patients with advanced breast cancer from 7 phase III and 1 phase II RCTs were eligible. The study arms used were palbociclib/ribociclib/abemaciclib or placebo in combination with letrozole or anastrozole or fulvestrant or other hormonal agents. The RR of all-grade side effects were as follows: diarrhea, 1.691 (95% CI: 1.220–2.345; P=.002); nausea, 1.632 (95% CI: 1.447–1.840; P<.001); vomiting, 1.684 (95% CI: 1.256–2.259, P=.001); stomatitis, 2.160 (95% CI: 1.332–3.503; P=.002); elevated AST, 1.832 (95% CI: 1.312–2.558; P<.001); and elevated ALT, 2.150 (95% CI: 1.649–2.803; P<.001). The RR of high-grade side effects were as follows: diarrhea, 2.592 (95% CI: 0.853–7.877; P=.093); nausea, 1.326 (95% CI: 0.589–2.988; P=.496); vomiting, 1.089 (95% CI: 0.479–2.476; P=.839); stomatitis, 2.097 (95% CI: 0.502–0.753; P=.310); elevated AST, 2.274 (95% CI: 1.173–4.410; P=.015); and elevated ALT, 3.988 (95% CI: 2.387–6.663; P<.001). Conclusions: Our study demonstrated that the risk of developing all grade GI toxicities and all grades of hepatic side effects including grade 3 and 4, was high in CDK 4/6 inhibitors group, compared to control arm, and prompt intervention with good supportive care is required.

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William J. Gradishar, Benjamin O. Anderson, Jame Abraham, Rebecca Aft, Doreen Agnese, Kimberly H. Allison, Sarah L. Blair, Harold J. Burstein, Chau Dang, Anthony D. Elias, Sharon H. Giordano, Matthew P. Goetz, Lori J. Goldstein, Steven J. Isakoff, Jairam Krishnamurthy, Janice Lyons, P. Kelly Marcom, Jennifer Matro, Ingrid A. Mayer, Meena S. Moran, Joanne Mortimer, Ruth M. O'Regan, Sameer A. Patel, Lori J. Pierce, Hope S. Rugo, Amy Sitapati, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, Erica M. Stringer-Reasor, Melinda L. Telli, John H. Ward, Jessica S. Young, Jennifer L. Burns and Rashmi Kumar

women with metastatic breast cancer and an intact primary tumor is systemic therapy, with consideration of surgery after initial systemic treatment of those women requiring palliation of symptoms or with impending complications, such as skin ulceration

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the recommendation regarding the use of bevacizumab (Avastin, Genentech/Roche) in the treatment of metastatic breast cancer. The NCCN Guidelines Panel for Breast Cancer affirmed its existing recommendation of bevacizumab in combination with

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Kyaw Z. Thein, Somedeb Ball, Sriman Swarup, Anita Sultan, Myo H. Zaw, Lukman Tijani, Sanjay Awasthi, Fred Hardwicke and Catherine Jones

Introduction: Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, has improved survival in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER 2)-negative advanced breast cancer. Despite remarkable efficacy, potential cardiac toxicities remain a concern. We undertook a combined analysis of randomized controlled trials (RCT) to estimate the incidence of prolongation of corrected QT interval (QTcF) associated with ribociclib. Methods: We performed systematic search of Embase, MEDLINE, and meeting abstracts till September 30, 2018, to find all phase 3 RCTs comparing ribociclib with other agents or placebo in patients with advanced breast cancer and reporting QTc prolongation as adverse event. Mantel-Haenszel method was used to calculate the pooled risk ratio (RR) and absolute risk difference (RD) with 95% CI. Fixed effects model was applied. Heterogeneity was assessed using I2 statistic. Results: Three phase III studies with 2,062 participants were included. Randomization ratio was 1 to 1 in MONALEESA-2 and 7 studies and 2 to 1 in MONALEESA-3 study. I2 statistic was 0, suggesting homogeneity across studies. Prolongation of QTcF >60 msec from baseline was observed in 72 patients (61 had post-baseline QTcF >480 msec) in ribociclib arm, compared to 7 in control arm. Pooled RR for prolongation of QTcF was 7.956 (95%CI: 3.683–17.187; P<.001) and RD was 0.055 (95%CI: 0.040–0.070; P<.001). The risk of having a post-baseline QTcF >480 msec was significantly higher with ribociclib vs control (pooled RR, 4.002; 95%CI: 2.161–7.412; P<.001; and RD, 0.039; 95%CI: 0.024–0.055; P<.001). A total of 16 (1.38%) patients in the ribociclib arm had dose reduction, interruption, or discontinuation due to QTcF prolongation, as opposed to 3 (0.33%) in control arm. Pooled RR and RD were statistically significant at 4.204 (95%CI: 1.333–3.260; P=.014) and 0.012 (95%CI: 0.004–0.021; P=.006), respectively. Conclusion: Advanced breast cancer patients may have cardiac dysfunction due to prior cardiotoxic chemotherapies. In our meta-analysis, ribociclib was associated with significantly higher risk of QTc prolongation and the resultant dosing inconsistencies and discontinuation. Early detection of this potential adverse event and timely intervention are critical.