Oncologists' Perspectives on Individualizing Dose Selection for Patients With Metastatic Cancer.

PURPOSE: Treatment goals for patients with metastatic cancer include prolongation and maintenance of quality of life. Patients and oncologists have questioned the current paradigm of initial dose selection for systemic therapy; however, data on oncologists' dose selection strategies and beliefs are lacking. METHODS: We conducted an electronic international survey of medical oncologists who treat patients with breast and/or gastrointestinal cancers. Survey questions addressed experiences with, and attitudes toward, dose reduction at initiation (DRI) of a new systemic therapy for patients with metastatic cancer. RESULTS: Among 3,099 eligible oncologists, 367 responded (response rate 12%). Most (52%) reported using DRI at least 10% of the time to minimize toxicities. Gastrointestinal specialists were more likely to report DRI ≥ 10% of the time (72% v 50% of generalists and 51% of breast specialists, P < .005). Of those who dose reduced ≥ 10% of the time, 89% reported discussing potential tradeoffs between efficacy and toxicity with patients. Overall, 65% agreed it is acceptable to lower starting doses to reduce side effects even if it compromises efficacy; younger clinicians were more likely to agree (P < .005). There was strong support (89%) for future trials to determine optimal effective, rather than maximum tolerated, dose. CONCLUSION: Oncology practice varies with regard to discussion and individualized selection of starting doses in the metastatic setting. This study demonstrates a need for consideration of shared decision making regarding initial dose selection and strong support among oncologists for clinical studies to define optimal dosing and best practices for individualizing care.

Geriatric assessment in older adults with non-Hodgkin lymphoma: A Young International Society of Geriatric Oncology (YSIOG) review paper.

Non-Hodgkin lymphoma (NHL) is a disease of older adults, with a median age at diagnosis of 67 years. Treatment in older adults with NHL is challenging. The aging process is associated with a decline in functional reserve that varies among individuals, and results in an increasing risk of treatment-related toxicity and mortality. Chronological age and performance status fail to capture the multidimensional and heterogeneous nature of the aging process. A geriatric assessment (GA) screens multiple geriatric domains and provides a more accurate assessment of functional reserve. Several abbreviated GA tools have been developed for use in oncology clinics and help identify patients at high risk for chemotherapy-related toxicity and mortality. In this review, we explore GA tools validated for use in patients with NHL. We discuss the evidence behind GA-guided treatment in NHL and present a suggested approach to assessing frailty in this patient population.

Use of prophylactic pegfilgrastim for chemotherapy-induced neutropenia in the US: A review of adherence to present guidelines for usage.

Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving chemotherapy. Pegfilgrastim is recommended for FN prophylaxis in patients with non-myeloid malignancies receiving a high-risk chemotherapy regimen, or an intermediate-risk regimen if one or more risk factors are present. The guidelines highlight the patient characteristics and chemotherapy regimens for solid tumors and hematologic malignancies that may influence a patient's overall risk of FN and may benefit from pegfilgrastim support. This review aimed to evaluate how pegfilgrastim use in patients with cancer receiving myelosuppressive chemotherapy in routine clinical practice aligns with evidence-based US guidelines. Examination of the literature revealed widespread deviation in relation to under- and over-prescribing, and timing of administration in US clinical practice. Pegfilgrastim is often over-prescribed in patients receiving palliative chemotherapy and those at low risk of FN. Potential under-prescribing of pegfilgrastim was also observed. In this literature search, data that appear to support same-day administration of pegfilgrastim were from uncontrolled studies that were limited in size. Analyses of healthcare claims data clearly favored next-day use, with statistically significant increases in FN incidence among patients receiving same-day pegfilgrastim versus those treated 1-4 days post-chemotherapy. Earlier-than-recommended administration typically occurs at the physician's discretion where next-day administration might present barriers to the patient receiving supportive therapy.There is a need to ensure appropriate prescribing to optimize patient outcomes, as deviation from the guideline recommendations was associated with increased incidence of FN and hospitalization.

Appropriate Systemic Therapy Dosing for Obese Adult Patients With Cancer: ASCO Guideline Update.

PURPOSE: To provide recommendations for appropriate dosing of systemic antineoplastic agents in obese adults with cancer. METHODS: A systematic review of the literature collected evidence regarding dosing of chemotherapy, immunotherapy, and targeted therapies in obese adults with cancer. PubMed and the Cochrane Library were searched for randomized controlled trials, meta-analyses, or cohort studies published from November 1, 2010, through March 27, 2020. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: Sixty studies, primarily retrospective, were included in the review. Overall, the evidence supported previous findings that obese adult patients tolerate full, body-size-based dosing of chemotherapy as well as nonobese patients. Fewer studies have addressed the dosing of targeted therapies and immunotherapies in relation to safety and efficacy in obese patients. RECOMMENDATIONS: The Panel continues to recommend that full, weight-based cytotoxic chemotherapy doses be used to treat obese adults with cancer. New to this version of the guideline, the Panel also recommends that full, approved doses of immunotherapy and targeted therapies be offered to obese adults with cancer. In the event of toxicity, the consensus of the Panel is that dose modifications of systemic antineoplastic therapies should be handled similarly for obese and nonobese patients. Important areas for future research include the impact of sarcopenia and other measures of body composition on optimal antineoplastic dosing, and more customized dosing based on pharmacokinetic or pharmacogenetic factors.Additional information is available at www.asco.org/supportive-care-guidelines.

A medicare database analysis of practice patterns in patients with mantle cell lymphoma.

INTRODUCTION: Although treatment approaches to younger fit patients with mantle cell lymphoma (MCL) are well-described, the optimal treatment of older or less fit patients with varying comorbidities is less clear. The objectives of this study were to examine first-line treatment patterns, and the impact of comorbidities and age on treatment choices and overall survival (OS) in a large, predominantly older, Medicare population. PATIENTS AND METHODS: In Medicare data from 1/1/2007-8/31/2015, 3,008 patients with MCL were identified. Data on age, gender, race, Charlson comorbidities, Charlson comorbidity index (CCI), timing of injectable MCL therapies, and OS were collected and analyzed. RESULTS: Median age of the study population was 75.5 (range, 33-107; 25th, 75th: 69.9, 81.5) years. Over half of the individuals had ≥two comorbidities. The CCI was 1-2 in 45%, and 3-4 in 26.6% of patients. Rituximab was the most commonly used agent, regardless of age or comorbidity, in the first 60 days following diagnosis, being administered to 40.2% of patients. In contrast, administration of cyclophosphamide, doxorubicin, vincristine, or bendamustine in the first 60 days after diagnosis was less common (17.9%, 13.1%, 17.2%, and 12%, respectively). Overall survival was 3.23 (range, 0.003-7.668) years, and decreased with increasing number of comorbidities. DISCUSSION: Our analysis of a real-world patient population with MCL found that older patients have a high rate of comorbidities which impact administered treatment and subsequent OS. Our findings can be used to prospectively guide treatment decisions in these older, frailer, non-transplant-eligible patients, considering the impact of age and comorbidities on such choices.

Frontline therapy with R-CHOP for diffuse large B-cell lymphoma: Where have we come (or not come)? A Perspective.

A major evolution in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) occurred almost two decades ago, with clinical trials demonstrating that the addition of rituximab (R) to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), which had been the "gold standard" of therapy since 1976, significantly improved outcome, including response rate and disease-free survival, of these patients. Since the adoption of R-CHOP, subsequent clinical trials have attempted to improve upon outcomes achieved with R-CHOP, with a variety of approaches examined. These have included dose intensification, which may be applicable in younger patients, but not in the many older or frailer patients with a disease with median age at diagnosis in the 60's. Newer anti-CD20 monoclonal antibodies have been substituted for rituximab in frontline regimens. A series of new agents, with unique mechanisms of action, have been added to the R-CHOP backbone. Rituximab-based, non-anthracycline regimens have been studied for older, more frail patients. The utility of maintenance therapy in responding patients has been re-examined, despite the lack of benefit found in the US Intergroup trial. Advances in molecular and genetic aspects of DLBCL have emerged since the seminal R-CHOP trials, demonstrating the DLBCL is not a single entity, but instead a spectrum of multiple disease subtypes. Attempts have been made to identify those patients at baseline who have poorer outcomes with standard approaches, utilizing laboratory and imaging findings. Moving forward, different risk-adapted treatment approaches will be studied to in an effort to improve overall outcome beyond R-CHOP.

Immunogenicity of Inactivated Varicella Zoster Vaccine in Autologous Hematopoietic Stem Cell Transplant Recipients and Patients With Solid or Hematologic Cancer.

BACKGROUND: In phase 3 trials, inactivated varicella zoster virus (VZV) vaccine (ZVIN) was well tolerated and efficacious against herpes zoster (HZ) in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and patients with solid tumor malignancies receiving chemotherapy (STMc) but did not reduce HZ incidence in patients with hematologic malignancies (HMs). Here, we describe ZVIN immunogenicity from these studies. METHODS: Patients were randomized to ZVIN or placebo (4 doses). Immunogenicity was assessed by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and VZV interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in patients receiving all 4 doses without developing HZ at the time of blood sampling. RESULTS: Estimated geometric mean fold rise ratios (ZVIN/placebo) by gpELISA and IFN-y ELISPOT ~28 days post-dose 4 were 2.02 (95% confidence interval [CI], 1.53-2.67) and 5.41 (95% CI, 3.60-8.12) in auto-HSCT recipients; 1.88 (95% CI, 1.79-1.98) and 2.10 (95% CI, 1.69-2.62) in patients with STMc; and not assessed and 2.35 (95% CI, 1.81-3.05) in patients with HM. CONCLUSIONS: ZVIN immunogenicity was directionally consistent with clinical efficacy in auto-HSCT recipients and patients with STMc even though HZ protection and VZV immunity were not statistically correlated. Despite a lack of clinical efficacy in patients with HM, ZVIN immunogenicity was observed in this population. Immunological results did not predict vaccine efficacy in these 3 populations. CLINICAL TRIAL REGISTRATION: NCT01229267, NCT01254630.

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma - Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007-2015.

INTRODUCTION: We characterized real-world treatment patterns in older (65-74 years) and oldest (75-85 years) patients with diffuse large B-cell lymphoma (DLBCL) receiving initial therapy (R-CHOP, non-R-CHOP regimens). Impact of comorbidities on treatment choice, and overall and progression-free survival (OS, PFS) were assessed by age. PATIENTS AND METHODS: Using the Humedica database, we identified 1436 newly diagnosed patients with DLBCL who received frontline therapy from 1/07-9/15. The 885 patients ≥65 years of age were further evaluated for baseline demographics, comorbidities, initial therapy, and PFS/OS. RESULTS: Of 885 patients, 406 (45.9%) were age 65-74, and 479 (54.1%) age 75-85, years. First line therapy was R-CHOP (61.8%) or non-R-CHOP (38.2%). Although Charlson Comorbidity Index (CCI) scores were similar at baseline, congestive heart failure and myocardial infarction were more common in those receiving non-R-CHOP regimens. Survival outcomes were superior for those receiving initial R-CHOP, versus non-R-CHOP, therapy (median PFS 53.9 versus 27.8 months; two-year PFS 71.2% versus 51.6%, p < .0001; median OS not reached versus 45 months; two-year OS 81.3% versus 62.9%, p < .0001, respectively). Only 10.4% (R-CHOP) and 12.1% (non-R-CHOP) of patients received second line therapies. Two-year OS by age (65-74, 75-85 years) was 66.4% and 39.1%, respectively with R-CHOP (p = .0045), and 74.3% and 54.5%, respectively with non-R-CHOP (p = .004), therapy. Age ≥ 75 years and CCI of 2+ were associated with shorter OS and PFS. CONCLUSIONS: This study identified real-world first line treatment patterns for older patients with DLBCL. Our findings support the feasibility of administering standard R-CHOP therapy, even to oldest patients with DLBCL.

Safety and efficacy of inactivated varicella zoster virus vaccine in immunocompromised patients with malignancies: a two-arm, randomised, double-blind, phase 3 trial.

BACKGROUND: Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies. METHODS: This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries. The trial included adult patients with solid tumour malignancies receiving chemotherapy and those with haematological malignancies, either receiving or not receiving chemotherapy. Patients were randomly assigned (1:1) to receive four doses of VZV vaccine inactivated by γ irradiation or placebo approximately 30 days apart. The patients, investigators, trial site staff, clinical adjudication committee, and sponsor's clinical and laboratory personnel were masked to the group assignment. The primary efficacy endpoint was herpes zoster incidence in patients with solid tumour malignancies receiving chemotherapy, which was assessed in the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of inactivated VZV vaccine or placebo). The primary safety endpoint was serious adverse events up to 28 days after the fourth dose in patients with solid tumour malignancies receiving chemotherapy. Safety endpoints were assessed in all patients who received at least one dose of inactivated VZV vaccine or placebo and had follow-up data. This trial is registered (NCT01254630 and EudraCT 2010-023156-89). FINDINGS: Between June 27, 2011, and April 11, 2017, 5286 patients were randomly assigned to receive VZV vaccine inactivated by γ irradiation (n=2637) or placebo (n=2649). The haematological malignancy arm was terminated early because of evidence of futility at a planned interim analysis; therefore, all prespecified haematological malignancy endpoints were deemed exploratory. In patients with solid tumour malignancies in the modified intention-to-treat population, confirmed herpes zoster occurred in 22 of 1328 (6·7 per 1000 person-years) VZV vaccine recipients and in 61 of 1350 (18·5 per 1000 person-years) placebo recipients. Estimated vaccine efficacy against herpes zoster in patients with solid tumour malignancies was 63·6% (97·5% CI 36·4 to 79·1), meeting the prespecified success criterion. In patients with solid tumour malignancies, serious adverse events were similar in frequency across treatment groups, occurring in 298 (22·5%) of 1322 patients who received the vaccine and in 283 (21·0%) of 1346 patients who received placebo (risk difference 1·5%, 95% CI -1·7 to 4·6). Vaccine-related serious adverse events were less than 1% in each treatment group. Vaccine-related injection-site reactions were more common in the vaccine group than in the placebo group. In the haematological malignancy group, VZV vaccine was well tolerated and estimated vaccine efficacy against herpes zoster was 16·8% (95% CI -17·8 to 41·3). INTERPRETATION: The inactivated VZV vaccine was well tolerated and efficacious for herpes zoster prevention in patients with solid tumour malignancies receiving chemotherapy, but was not efficacious for herpes zoster prevention in patients with haematological malignancies. FUNDING: Merck & Co, Inc.

Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA.

AIM: To evaluate treatment patterns of diffuse large B-cell lymphoma (DLBCL). PATIENTS & METHODS: First-line and relapsed/refractory treatment patterns and survival outcomes following first-line therapy in adult patients newly diagnosed with DLBCL were evaluated. RESULTS: A total of 1436 DLBCL patients initiated treatment and mainly received a combination regimen versus monotherapy (92.1 vs 7.9%). Patients who received monotherapy were older with more comorbidities and had shorter progression-free survival than patients receiving combination therapy (median: 31.3 vs 55.8 months). In the second-line setting (n = 164), rituximab-based combination regimens were most common; 25% underwent stem cell transplantation, and were younger with fewer comorbidities. CONCLUSION: These results illustrate the need for new treatment options for patients unable to tolerate initial combination therapy and transplant-ineligible patients who require salvage therapy.

Mortality by a proxy performance status as defined by a claims-based measure for disability status in older patients with newly diagnosed multiple myeloma in the United States.

OBJECTIVES: We applied a claims-based definition of disability status as a proxy for performance status (PS) and examined associations between PS and mortality in a population-based cohort of older US adults with multiple myeloma (MM). MATERIALS AND METHODS: We identified older (≥66 years) Medicare beneficiaries diagnosed with MM January 1, 2008-December 31, 2011, who began first-line therapy in the study period (through December 31, 2012). We estimated predicted probability of poor PS for each patient at initiation of each line up to fourth-line therapy, classified as poor (predicted probability ≥0.11) or good (<0.11) PS, and examined mortality. Crude overall survival was estimated using the Kaplan-Meier method with log-rank test for survival comparison between PS groups. Cox proportional hazards models evaluated the association between poor PS and mortality risk, adjusted for baseline characteristics by lines of therapy. RESULTS: Of 12,547 patients, 5841, 2372, and 819 initiated second-, third-, and fourth-line in the study period. Poor PS proportions were 16.6%, 21.8%, 18.4%, and 18.2% at each line. Crude overall survival was worse for poor PS patients across lines (P < 0.01 for each). Adjusted hazards ratios (95% CI) of mortality for patients with poor versus good PS were 1.28 (1.18-1.40), first-line; 1.55 (1.36-1.77), second-line; 1.35 (1.10-1.65), third-line; 1.22 (0.84-1.76), fourth-line. CONCLUSION: The claims-based prediction model for disability status performed as expected as a proxy for PS in older Medicare patients with MM. PS was an independent risk factor for mortality. Further studies assessing the effect of PS on mortality by therapies are warranted.

Treatment Patterns and Survival Outcomes in Patients With Follicular Lymphoma: A 2007 to 2015 Humedica Database Study.

BACKGROUND: Few studies have evaluated real-world treatment patterns and survival in follicular lymphoma (FL). This study evaluated these outcomes among newly diagnosed patients with FL in routine clinical care. PATIENTS AND METHODS: A retrospective study was conducted in newly diagnosed patients with FL from Humedica, a large United States electronic medical record database, from January 1, 2008 to July 31, 2015. Patients were followed from treatment initiation until death, loss to follow-up, or end of study (September 30, 2015). Treatment patterns were assessed in the follow-up period. Progression-free survival (PFS) and overall survival (OS) at 2 years were evaluated in the overall population using Kaplan-Meier analyses. OS was also compared between patients with and without evidence of disease progression within 2 years following first-line therapy (ie, early progressors vs. non-early progressors). RESULTS: A total of 1346 patients were included in the study, with most patients receiving rituximab-based regimens. Fewer early progressors received rituximab-based regimens. Across all lines, combination therapies predominated, particularly bendamustine + rituximab. Following first-line therapy, OS was 86.9% at 2 years, and median OS was not reached. Two-year PFS after first-line therapy was 64.6%, and median PFS was 48.1 months (95% confidence interval, 39.4-58.4 months). OS at 2 years was 76.8% among early progressors versus 90.4% among non-early progressors (P < .001); the median OS was not reached in both groups. CONCLUSION: In routine clinical practice, rituximab-based regimens predominated; however, utilization of these regimens differed among early and non-early progressors. The assessment of survival outcomes also highlights the negative impact of early progression on OS in the rituximab-era.

Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA.

AIM: Evaluate healthcare costs and utilization of treated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. MATERIALS & METHODS: Adults with newly diagnosed DLBCL and FL between 1 January 2008 and 31 October 2015 were identified in the Optum™ claims database. Healthcare costs and utilization were assessed from diagnosis date until end of follow-up. RESULTS: A total of 1267 DLBCL- and 1595 FL-treated patients were identified. Mean per-patient, per-month cost during follow-up was US$11,890 for DLBCL and US$10,460 for FL. Healthcare costs and utilization decreased from year 1 to 2 following diagnosis, due to a decrease in chemotherapy services, inpatient admissions and other outpatient services. CONCLUSION: The economic burden of treated DLBCL and FL is considerable, especially in the first year following diagnosis.

Treatment of mantle cell lymphoma in older adults.

Mantle cell lymphoma (MCL) predominantly affects older adults, with a median age at diagnosis of 70years. A frequently aggressive yet incurable lymphoma, the goal of therapy for MCL is to turn a potentially life-threatening illness into a chronic disease with prolonged periods of remission. Large randomized trial data supports the standard treatment in younger patients of cytarabine-based induction followed by autologous stem cell transplant. Most patients will not be eligible for this intensive approach based on older age, comorbidities, and functional status, making the geriatric assessment an essential step in choosing the appropriate strategy. For these older patients, an increasing number of chemotherapy and non-chemotherapy based therapies are available that allow oncologists to better tailor treatment to the fitness of the patient. We will review treatment options for older patients with MCL in the first line and relapsed/refractory settings, highlighting the available evidence for providing longer progression-free intervals while also minimizing the adverse effects of unduly aggressive treatment.

The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study.

Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001). This prolonged survival was in the subgroups of patients aged 60-69 years (p< .0001) and those with 11q deletion (p < .0001). Those exposed to AO were more likely to be treated with fludarabine, chlorambucil and rituximab (38 vs. 21%, p < .001) and bendamustine plus rituximab (25 vs. 18%, p = 0.039) as first line therapy. Exposure to AO was not associated with either poor prognostic factors or shortened overall survival in our large veteran population with CLL.

The impact of age and comorbidities on practice patterns and outcomes in patients with relapsed/refractory multiple myeloma in the era of novel therapies.

OBJECTIVES: One-third of patients with multiple myeloma (MM) are diagnosed at age≥75years. Older patients have increased incidence of cardiovascular disease (CVD) and renal insufficiency (RI), hallmark complications of MM. We examined cumulative incidence of CVD and RI in relapsed/refractory MM (RRMM) and outcomes by age and RI/CVD. MATERIALS AND METHODS: Retrospective cohort study using a large US electronic medical records database of adult patients with RRMM initiating first- and second-line therapy (2LT) between 1/2008-06/2015. RI and CVD comorbidities were based on diagnosis codes and/or lab values. RESULTS: Among 628 patients, 37.1% were ≥75years. Cumulative incidence of CVD and/or RI increased from 47.7% at MM diagnosis to 67.8% at first relapse. Age≥75years had a trend toward higher risk of relapse post 2LT, proxied by time to next treatment (TTNT), (adjusted HR: 1.28; 95% CI: 1.00, 1.65; P=0.05). TTNT was significantly higher with comorbid CVD+RI (adjusted HR: 1.50; 95% CI: 1.11, 2.02; P<0.01). Age≥75years, RI, CVD, and CVD+RI were associated with increased mortality risk from 2LT initiation; adjusted HR: 1.66 (95% CI: 1.19, 2.33; P<0.01), 1.51 (95% CI: 1.01, 2.26; P=0.04), 1.75 (95% CI: 1.03, 2.96; P=0.04), and 1.95 (95% CI: 1.29, 2.93; P<0.01), respectively. CONCLUSION: Despite treatment with novel agents for RRMM in 86% of patients, an outcome gap persists for older patients and those with RI and/or CVD. Personalized treatment approaches that account for age and comorbidities, and further evaluation of innovative regimens and dosing schedules, are needed to improve outcomes for these patients.

The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: Results from Cancer and Leukemia Group B (CALGB) trial 49907 (Alliance A151436).

OBJECTIVE: Actual weight-based (AWB) chemotherapy dosing is recommended for obese patients in the 2012 ASCO Clinical Practice Guideline. CALGB 49907, which utilized ABW-based adjuvant chemotherapy dosing, was a phase 3 trial in women age≥65years with early stage breast cancer, providing the opportunity to examine impact of such dosing on toxicities and outcome in older patients with breast cancer. MATERIALS AND METHODS: Adverse event data were available for 615 of 633 enrolled patients. Objectives were to assess grade≥3 hematologic/non-hematologic toxicities by treatment arm, age, study entry BSA/BMI, and relapse-free (RFS) and overall survival (OS) by BSA/BMI. RESULTS: The 615 patients were sub-grouped by BSA (quartiles) and standard BMI categories, with BMI underweight/normal weight categories combined. Overall, grade≥3 non-hematologic and hematologic toxicities occurred in 39.8% and 28.3% of patients, respectively. There were no significant differences in grade≥3 toxicities among BSA quartiles. However, more grade≥3 hematologic toxicities occurred in the underweight/normal weight BMI subgroup compared to overweight/obese subgroups (p=0.048). Type of chemotherapy and age had no impact on toxicity occurrence by BSA/BMI categories. RFS was superior in the 25th-50th BSA percentile patients in univariate analysis (p=0.042), as was OS in both univariate and multivariate analyses (p=0.007, p=0.009, respectively). No differences in RFS or OS were found by BMI categories. CONCLUSION: Obesity was not correlated with adverse relapse or survival outcome, and grade≥3 toxicities were not greater with ABW-based dosing. This supports safety and efficacy of ABW-based dosing as per the 2012 ASCO clinical practice guideline. ClinicalTrials.gov Identifier: NCT00024102 (49907).