Perspectives on shorter durations of anti-HER2 therapy in early-stage HER2-positive breast cancer: a patient survey.

PURPOSE: Despite previous studies proposing shorter durations of anti-HER2 therapy for selected patients with HER2-positive early breast cancer (EBC), 12-months remains standard of care. A survey was performed to assess patient perspectives and willingness to participate in studies evaluating shorter durations of anti-HER2 therapy. METHODS: Patients with HER2-positive EBC completing or having previously completed anti-HER2 therapy, were recruited by healthcare professionals at The Ottawa Hospital Cancer Centre to participate in an anonymous online survey. The primary objective was to learn about patients' perspectives on shorter durations (less than 12-months) of anti-HER2 therapy. Secondary objectives were to explore patients' interest in clinical trials of shorter durations of anti-HER2 therapy and the degree of increased breast cancer risk they would accept with a shorter treatment duration. RESULTS: Responses were received from 94 eligible patients. Most patients received Trastuzumab alone (78%, 73/94), while 13% (12/94) received trastuzumab and pertuzumab. Side effects were experienced by 52% (46/89), the most common being; fatigue (61%, 28/46), myalgia (37%, 17/46), and diarrhea (24%, 11/46). Most patients (88%, 78/89) did not find treatment bothersome. Regarding perspectives on shorter durations of anti-HER2 therapy, most (79%, 74/94) respondents stated they would agree to less treatment if it were possible to receive fewer treatments with the same cancer benefits. 56% of patients were interested in clinical trials, however, about half stated they would not be accepting of any increase in breast cancer recurrence risk. CONCLUSION: Trials to investigate who can safely and effectively be treated with shorter durations of anti-HER2 therapy are needed. This study provides important insights to patients' perspectives on shorter durations of anti-HER2 treatment, and their concerns regarding potential increased cancer risk with less treatment.

Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients.

BACKGROUND: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm "Bordier" core needle. We examined the feasibility of using a 2 mm "Jamshidi™" core needle as a more practical and less invasive technique. METHODS: Patients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry. RESULTS: Twelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size. DISCUSSION: Our results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.

Canada follows the US in the rise of bilateral mastectomies for unilateral breast cancer: a 23-year population cohort study.

INTRODUCTION: The use of contralateral prophylactic mastectomy (CPM) continues to grow despite the absence of evidence supporting a survival benefit. This study's objectives were to (1) describe the trends in the rates of unilateral and bilateral mastectomy (BM) in women diagnosed with unilateral breast cancer (UBC) in Ontario, Canada from 1991 to 2013, and (2) identify factors associated with BM to treat UBC. METHODS: This retrospective cohort analysis included all women aged 18 and older diagnosed with UBC between January 1991 and December 2013. Health administrative data from the Institute for Clinical Evaluative Sciences, the Ontario Cancer Registry, and the Discharge Abstract Database were used to identify all breast cancer and mastectomy cases. Age-adjusted mastectomy rates were plotted over time. Univariable and multivariable analyses included clinically significant covariates. RESULTS: From 1991 to 2013 there were 172,165 cases of UBC and 64,886 mastectomies (37.7%) performed in Ontario. 13.6% of the mastectomies were bilateral. BM rates increased over sixfold (from 4 to 25%) across all age groups under age 70 over a 23-year period. On multivariable analysis, younger age, higher income, rural community, earlier breast cancer stage, lobular histology, availability of reconstruction and teaching hospitals were associated with increased odds of BM. CONCLUSIONS: This is the largest population study of breast cancer patients in Canada and shows an increasing rate of BM for UBC. The results are similar to those already described in the US and highlight the importance of continued efforts to promote efficient communication and evidence-based decision-making prior to breast surgery.

A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting.

PURPOSE: Despite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV). METHODS: This multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1-4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events. RESULTS: 218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0-5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1-46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2-32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001). CONCLUSION: In patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

Practical update for the use of bone-targeted agents in patients with bone metastases from metastatic breast cancer or castration-resistant prostate cancer.

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphosphonates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of metastatic bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: ■ What are btas, and what is their efficacy?■ What are their common toxicities?■ When should they be initiated?■ How do we choose the appropriate bta?■ What is the appropriate dose, schedule, and duration of btas?

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer.

BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS: Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.

Exploring reasons for overuse of contralateral prophylactic mastectomy in Canada.

Background: Contralateral prophylactic mastectomy (cpm) in women with known unilateral breast cancer (bca) has been increasing despite the lack of supportive evidence. The purpose of the present study was to identify the determinants of cpm in women with unilateral bca. Methods: This qualitative descriptive study used semi-structured interviews informed by the Theoretical Domains Framework. We interviewed 74 key informants (surgical oncologists, plastic surgeons, medical oncologists, radiation oncologists, nurses, women with bca) across Canada. Interviews were analyzed using thematic analysis and an analysis for shared and discipline-specific beliefs. Results: In total, 58 factors influencing the use of cpm were identified: 26 factors shared by various health care professional groups, 15 discipline-specific factors (identified by a single health care professional group), and 17 factors shared by women with unilateral bca. Health care professionals identified more factors discouraging the use of cpm (n = 26) than encouraging its use (n = 15); women with bca identified more factors encouraging use of cpm (n = 12) than discouraging its use (n = 5). The factor most commonly identified by health care professionals that encouraged cpm was lack of awareness of existing evidence or guidelines for the appropriate use of cpm (n = 44, 75%). For women with bca, the factor most likely influencing their decision for cpm was wanting a better esthetic outcome (n = 14, 93%). Conclusions: Multiple factors discouraging and encouraging the use of cpm in unilateral bca were identified. Those factors identify potential individual, team, organization, and system targets for behaviour change interventions to reduce cpm.

Patient decision aid for contralateral prophylactic mastectomy for use in the consultation: a feasibility study.

Background: Rates of contralateral prophylactic mastectomy (cpm) continue to rise internationally despite evidence-based guidance strongly discouraging its use in most women with unilateral breast cancer. The purpose of the present study was to develop and assess the feasibility of a knowledge translation tool [a patient decision aid (da)] designed to enhance evidence-informed shared decision-making about cpm. Methods: A consultation da was developed using the Ottawa Patient Decision Aid Development eTraining in consultation with clinicians and knowledge translation experts. The final da was then assessed for feasibility with health care professionals and patients across Canada. The assessment involved a survey completed online (health care professionals) or by telephone (patients). Survey data were analyzed using descriptive statistics for closed-ended questions and qualitative content analysis for open-ended questions. Results: The 51 participants who completed the survey included 39 health care professionals and 12 patients. The da was acceptable; 88% of participants viewed it as having the right amount of information or slightly more or less information than they would like. Almost all participants (98%) felt that the da would prepare patients to make better decisions. The aid was perceived to be usable, with 73% of participants stating that they would be willing to use or share the da. Conclusions: The cpm patient da developed for the present study was viewed by health care professionals and patients across Canada to be acceptable and usable during the clinical consultation. It holds promise as a knowledge translation tool to be used by clinicians in consultation with women who have unilateral breast cancer to enhance evidence-informed and shared decision-making with respect to undergoing cpm.

Epidermal growth factor receptor inhibitor-induced hypomagnesemia: a survey of practice patterns among Canadian gastrointestinal medical oncologists.

Background: The optimal management of hypomagnesemia (hMg) induced by epidermal growth factor receptor inhibitors (egfris) for advanced colorectal cancer is unclear. We surveyed gastrointestinal medical oncologists in Canada to determine practice patterns for the management of egfri-induced hMg. Methods: Based on distribution lists from the Eastern Canadian Colorectal Cancer Consensus Conference and the Western Canadian Gastrointestinal Cancer Consensus Conference, medical oncologists were invited to participate in an online questionnaire between November 2013 and February 2014. Results: From the 104 eligible physicians, 40 responses were obtained (38.5%). Panitumumab was more commonly prescribed than cetuximab by 70% of respondents, with 25% prescribing cetuximab and panitumumab equally. Most respondents obtain a serum magnesium level before initiating a patient on an egfri (92.5%) and before every treatment (90%). Most use a reactive strategy for magnesium supplementation (90%) and, when using supplementation, favour intravenous (iv) alone (40%) or iv and oral (45%) dosing. Magnesium sulfate was used for iv replacement, and the most common oral strategies were magnesium oxide (36.4%) and magnesium rougier (18.2%). Under the reactive strategy, intervention occurred at hMg grade 1 (70.3%) or grade 2 (27%). Of the survey respondents, 45% felt that 1-5 of their patients have ever developed symptoms attributable to hMg, and 35% have had to interrupt egfri therapy because of this toxicity, most commonly at grade 3 (30%) or grade 4 (45%) hMg. The most important question about egfri-induced hMg was its relevance to clinical outcomes (45%) and its symptoms (37.5%). Conclusions: In Canada, various strategies are used in the management of egfri-induced hMg, including prophylactic and reactive approaches that incorporate iv, oral, or a combination of iv and oral supplementation. Clinicians are concerned about the effect of hMg on clinical outcomes and about the symptoms that patients experience as a result of this toxicity.

Optimizing vascular access for patients receiving intravenous systemic therapy for early-stage breast cancer-a survey of oncology nurses and physicians.

Background: Despite advances in systemic therapy choices for patients with early-stage breast cancer, optimal practices for intravenous (IV) access remain unknown. That lack of knowledge holds particularly true for the use of central venous access devices (cvads) such as peripherally inserted central catheters (piccs) and implanted vascular access devices (ports). Methods: Using a survey of Canadian oncologists and oncology nurses responsible for the care of breast cancer patients, we evaluated current access practices, perceptions of complications, and perceptions of risk, and we estimated complication rates and evaluated perceived risk factors for lymphedema. Results: Survey responses were received from 25 physicians and 57 oncology nurses. Administration of trastuzumab or an anthracycline was associated with a higher likelihood of a cvad being recommended. Other factors associated with recommendation of a cvad included prior difficult IV access and a recommendation from the chemotherapy nurse. Although the complication rates perceived to be associated with the use of piccs and ports remained high, respondents felt that cvads might improve patient quality of life. Risk factors perceived to be associated with the risk of lymphedema were axillary lymph node dissection, radiation to the axilla, and line-associated infection. Factors known to be unrelated to lymphedema risk (specifically, blood draws and blood pressure measurement) continue to be perceived as posing a higher risk. Conclusions: Despite widespread use of chemotherapy for patients with breast cancer, the type of venous access used for treatment varies significantly, as do perceptions about the risks of cvad use and the risk for lymphedema development. Further prospective studies are needed to identify best-practice strategies.

Perceptions of vascular access for intravenous systemic therapy and risk factors for lymphedema in early-stage breast cancer-a patient survey.

Background: The choice of vascular access for systemic therapy administration in breast cancer remains an area of clinical equipoise, and patient preference is not consistently acknowledged. Using a patient survey, we evaluated the patient experience with vascular access during treatment for early-stage breast cancer and explored perceived risk factors for lymphedema. Methods: Patients who had received systemic therapy for early-stage breast cancer were surveyed at 2 Canadian cancer centres. Results: Responses were received from 187 patients (94%). The route of vascular access was peripheral intravenous line (IV) in 24%, a peripherally inserted central catheter (picc) in 42%, and a surgically inserted central catheter (port) in 34%. Anthracycline-based regimens were associated with a greater use of central vascular access devices (cvads- that is, a picc or port; 86/97, 89%). Trastuzumab use was associated with greater use of ports (49/64, 77%). Although few patients (7%) reported being involved in the decisions about vascular access, most were satisfied or very satisfied (88%) with their access type. Patient preference centred mainly on avoiding delays in the initiation of chemotherapy. Self-reported rates of complications (183 evaluable responses) were infiltration with peripheral IVs (9/44, 20%), local skin infections with piccs (7/77, 9%), and thrombosis with ports (4/62, 6%). Perceived risk factors for lymphedema included use of the surgical arm for blood draws (117/156, 75%) and blood pressure measurement (115/156, 74%). Conclusions: Most patients reported being satisfied with the vascular access used for their treatment. Improved education and understanding about the evidence-based requirements for vascular access are needed. Perceived risk factors for lymphedema remain variable and are not evidence-based.

Optimal sequence of adjuvant endocrine and radiation therapy in early-stage breast cancer - A systematic review.

IMPORTANCE: Clinical equipoise exists around the optimal time to start adjuvant endocrine therapy in patients who will receive post-operative radiotherapy for breast cancer. Concerns continue to exist regarding potential reduced efficacy, or increased toxicity, when radiation, and endocrine therapy are administered concurrently. OBJECTIVE: To perform a systematic review of studies comparing outcomes between sequential and concurrent adjuvant radiation and endocrine therapy in early-stage breast cancer. All modalities of radiation therapy were considered, and endocrine therapy could be either tamoxifen or an aromatase inhibitor. Outcomes of interest included; local, regional or distant recurrence, overall survival and treatment-related toxicities. EVIDENCE REVIEWED: PubMed, Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1946 to December 2017. Two reviewers independently assessed each citation using the criteria outlined above. Study quality was assessed using the Cochrane Collaboration's tool for prospective studies, and the Newcastle-Ottawa scale for retrospective studies. FINDINGS: Of 2137 unique citations identified, 13 met eligibility criteria. Eleven were unique studies (7569 patients), while 2 of the studies were updated analyses of previous studies. Studies evaluated the timing of adjuvant radiation, and tamoxifen (5 studies, 1550 patients), or aromatase inhibitors (6 studies, 6019 patients). We identified 1 complete randomized clinical trial (150 patients), and 5 retrospective studies (1580 patients), in addition to conference abstracts (5 studies, 5839 patients). Overall, none of the studies showed a significant difference in efficacy, or toxicity, with concurrent versus sequential treatment. However, given the significant heterogeneity of the study populations, it was not possible to conduct a meta-analysis. CONCLUSIONS AND RELEVANCE: In the absence of high quality data, adequately powered randomized trials are required to answer this important clinical question.

Effects on bone resorption markers of continuing pamidronate or switching to zoledronic acid in patients with high risk bone metastases from breast cancer.

BACKGROUND: Switching patients who remain at high risk of skeletal related events (SREs) despite pamidronate to the more potent bisphosphonate zoledronate, may be an effective treatment strategy. As part of a previously reported clinic study in this setting, we evaluated whether biomarkers for bone resorption, such as Bone-Specific Alkaline Phosphatase (BSAP), bone sialoprotein (BSP), and N-terminal telopeptide (NTX) correlated with subsequent SRE risk. METHODS: Breast cancer patients who remained at high risk of SREs despite at least 3 months of q.3-4 weekly pamidronate were randomized to either continue on pamidronate or to switch to zoledronate (4 mg) once every 4 weeks for 12-weeks. High risk bone metastases were defined by either: occurrence of a prior SRE, bone pain, radiologic progression of bone metastases and/or serum C-terminal telopeptide (CTx) levels > 400 ng/L despite pamidronate use. Serum samples were collected at baseline and weeks 1, 4, 8 and 12 (CTx and BSAP) and baseline and week 12 (NTx and BSP), and all putative biomarkers were measured by ELISA. Follow up was extended to 2 years post trial entry for risk of subsequent SREs. The Kaplan-Meier method was used to estimate time-to-event outcomes. Generalized estimating equations (GEE) were used to evaluate if laboratory values over time or the change in laboratory values from baseline were associated with having a SRE within the time frame of this study. RESULTS: From March 2012 to May 2014, 76 patients were screened, with 73 eligible for enrolment. All 73 patients were available for biochemical analysis, with 35 patients receiving pamidronate and 38 patients receiving zoledronate. The GEE analysis found that no laboratory value was associated with having a subsequent SRE. Interaction between visit and laboratory values was also investigated, but no interaction effect was statistically significant. Only increased number of lines of prior hormonal treatment was associated with subsequent SRE risk. CONCLUSION: Our analysis failed to find any association between serum BSAP, BSP, CTx or NTx levels and subsequent SRE risk in this cohort of patients. This lack of correlation between serum biomarkers and clinical outcomes could be due to influences of prior bisphosphonate treatment or presence of extra-osseous metastases in a significant proportion of enrolled patients. As such, caution should be used in biomarker interpretation and use to direct decision making regarding SRE risk for high risk patients in this setting.

A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213.

BACKGROUND: Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and early clinical activity in breast cancer and synergistic cytotoxic activity with microtubule targeting agents. This multicentre, randomized, phase II trial was undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel for patients with metastatic breast cancer (mBC). METHODS: Following a safety run-in of 7 patients, 74 women with previously treated mBC were randomized either to paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 4 weeks plus pelareorep 3 × 1010 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4 weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate, overall survival (OS), circulating tumour cell counts, safety, and exploratory correlative analyses. All comparisons used a two-sided test at an alpha level of 20%. Survival analyses were adjusted for prior paclitaxel. RESULTS: Final analysis was performed after a median follow-up of 29.5 months. Pelareorep was well tolerated. Patients in Arm A had more favourable baseline prognostic variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80% CI 0.76-1.43, P = 0.87). There was no difference in response rate between arms (P = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46-0.91, P = 0.1). CONCLUSIONS: This first, phase II, randomized study of pelareorep and paclitaxel in previously treated mBC did not show a difference in PFS (the primary endpoint) or RR. However, there was a significantly longer OS for the combination. Further exploration of this regimen in mBC may be of interest.

The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting.

BACKGROUND: Despite the availability of effective antiemetics and evidence-based guidelines, up to 40% of cancer patients receiving chemotherapy fail to achieve complete nausea and vomiting control. In addition to type of chemotherapy, several patient-related risk factors for chemotherapy-induced nausea and vomiting (CINV) have been identified. To incorporate these factors into the optimal selection of prophylactic antiemetics, a repeated measures cycle-based model to predict the risk of ≥ grade 2 CINV (≥2 vomiting episodes or a decrease in oral intake due to nausea) from days 0 to 5 post-chemotherapy was developed. PATIENTS AND METHODS: Data from 1198 patients enrolled in one of the five non-interventional CINV prospective studies were pooled. Generalized estimating equations were used in a backwards elimination process with the P-value set at <0.05 to identify the relevant predictive factors. A risk scoring algorithm (range 0-32) was then derived from the final model coefficients. Finally, a receiver-operating characteristic curve (ROCC) analysis was done to measure the predictive accuracy of the scoring algorithm. RESULTS: Over 4197 chemotherapy cycles, 42.2% of patients experienced ≥grade 2 CINV. Eight risk factors were identified: patient age <60 years, the first two cycles of chemotherapy, anticipatory nausea and vomiting, history of morning sickness, hours of sleep the night before chemotherapy, CINV in the prior cycle, patient self-medication with non-prescribed treatments, and the use of platinum or anthracycline-based regimens. The ROC analysis indicated good predictive accuracy with an area-under-the-curve of 0.69 (95% CI: 0.67-0.70). Before to each cycle of therapy, patients with risk scores ≥16 units would be considered at high risk for developing ≥grade 2 CINV. CONCLUSIONS: The clinical application of this prediction tool will be an important source of individual patient risk information for the oncology clinician and may enhance patient care by optimizing the use of the antiemetics in a proactive manner.