David Cox

Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study.

Background1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions.MethodsPatients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables.ResultsEligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p < 0.05).ConclusionsPatients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.

Comparative Effectiveness Analysis of Monotherapy With Cytotoxic Agents in Triple-negative Metastatic Breast Cancer in a Community Setting

PURPOSE There has been considerable progress in the treatment of metastatic breast cancer. However, the identification of optimal cytotoxic agents in patients with triple-negative breast cancer (TNBC) (negative for hormone receptors and human epidermal growth factor receptor 2) remains a therapeutic challenge. We conducted a comparative effectiveness analysis of 4 cytotoxic agents in patients with TNBC. METHODS We retrospectively identified patients who received single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine from 19 community oncology clinics across the United States. Data collection included baseline patient and disease characteristics, prior therapies, performance status, duration of current therapy, growth-factor use and other supportive care, and dose-limiting toxicities and associated dose reductions or delays or skipped doses. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was estimated using the Kaplan-Meier method and Cox proportional hazards modeling adjusted for clustering on the practice site. To control for selection bias, which is inherent in observational studies, a propensity score-weighted TTF analysis was also conducted. FINDINGS Data from 225 patients were included in the analysis (eribulin, 47 patients; capecitabine, 69; gemcitabine, 56; and vinorelbine, 53). The median age of each group was <60 years, with the exception of the gemcitabine group (63 years). The 4 groups were comparable with respect to age, performance status, duration of disease-free survival, presence of comorbidities, and hemoglobin level before the start of chemotherapy. Median lines of therapy of eribulin, capecitabine, gemcitabine, and vinorelbine and were 4th, 2nd, 3rd, and 3rd, respectively. The median durations of treatment were ~2 months with eribulin, capecitabine, and gemcitabine compared with 1.6 months with vinorelbine. Using eribulin as the reference drug, and with adjustment for line of therapy and associated prognostic factors, the propensity score-weighted Cox regression analysis did not identify significant between-treatment differences in TTF (hazard ratios [95% CI] vs eribulin: capecitabine, 1.15 [0.75-1.76]; gemcitabine, 0.62 [0.34-1.13]; and vinorelbine, 1.0 [0.67-1.67]). IMPLICATIONS In this assessment of patients with TNBC treated in a community oncology setting, eribulin was utilized in later lines compared with the other agents. However, comparable drug activity was reported among the 4 agents.

Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data

Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)—a new NK1 RA—and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug–drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates.

A comparison of toxicity and health care resource use between eribulin, capecitabine, gemcitabine, and vinorelbine in patients with metastatic breast cancer treated in a community oncology setting

Background Capecitabine (C), gemcitabine (G), and vinorelbine (V) are commonly used as single agents in patients with metastatic breast cancer. Eribulin (E) is one of the most recent cytotoxic agents to gain regulatory approval for metastatic breast cancer in the United States as a single agent. EMBRACE – a large randomized trial demonstrated the safety and overall survival benefit of eribulin in heavily pretreated metastatic breast cancer patients compared to treatment of physicians choice. In this analysis, toxicity and the associated health care resource use were compared between the four agents in a sample of metastatic breast cancer patients treated in a US community oncology setting. Methods This study identified 411 patients (C=144, G=81, V=96, and E=90) who were treated in 19 community oncology clinics over the preceding two-year period. Data collection included baseline patient and disease characteristics, duration of therapy, use of supportive care drugs, type of dose limiting toxicities, and their impact on overall health care resource use. Results The median lines of therapy for C, G, V, and E were second, third, third, and fourth, respectively. Patients were comparable with respect to baseline comorbidities, performance status, serum creatinine, hemoglobin, neutrophil, and platelet counts. The proportion reporting at least one adverse event (any grade) with C, G, V, and E was 45%, 65%, 75%, and 63%. The most commonly reported toxicities (regardless of grade) for C, G, and V were diarrhea (19.4%), anemia (34.6%), and neutropenia (50.0%), respectively. The most common toxicity for E was neutropenia (32.2%). Overall, 5.6%, 19.8%, 22.9%, and 22.2% of patients receiving C, G, V, and E required at least one medical intervention to manage a toxic event. Toxicity was the cause of treatment discontinuation in 25.7%, 8.6%, 11.5%, and 8.9% of C, G, V, and E patients, respectively. The primary cause for treatment discontinuation in all four cohorts was disease progression. Conclusions Eribulin demonstrated a comparable patient safety profile to gemcitabine and vinorelbine, even when administered after three lines of prior therapies. Capecitabine was generally used in earlier lines, had less neutropenia and anemia, but more treatment discontinuations due to toxicity.

Comparative clinical effectiveness of various 5-HT3 RA antiemetic regimens on chemotherapy-induced nausea and vomiting associated with hospital and emergency department visits in real world practice

PurposeThe aim of this study was to compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT3 RAs in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions.MethodsPharMetrics claims database was used to identify patients diagnosed with breast cancer (BC) who were initiated on cyclophosphamide-based adjuvant chemotherapy or with lung cancer (LC) initiated on carboplatin-based or cisplatin-based chemotherapy between 2005 and 2008. Patients were stratified in two groups: those initiated and maintained on palonosetron versus those treated with any other 5-HT3 RA regimens in the 6-month post first chemotherapy. Risk for CINV events, identified by ICD-9-CM for nausea, vomiting, and/or dehydration, were estimated using logistic regressions, controlling for age, gender, comorbidity, and total chemotherapy doses or days.ResultsOf the 4,868 cyclophosphamide-treated BC, 5,414 carboplatin-treated LC, and 1,692 cisplatin-treated LC identified, there were 1,864 BC (38.5%), 1,806 carboplatin-treated LC (33.4%), and 390 cisplatin-treated LC (23.0%) in the palonosetron-only group. Palonosetron-only group had significantly lower probability of CINV events associated with ED/hospital admissions in all three cohorts (3.5% vs. 6.3% in BC, 9.5% vs. 13.8% in carboplatin-treated LC, and 16.4% vs. 22.6% in cisplatin-treated LC, all at p < 0.05). Logistic regressions found palonosetron-only group had significantly lower risk of CINV events (odds ratios = 0.550, 0.653, and 0.689 in BC, carboplatin-treated LC and cisplatin-treated LC, respectively, p < 0.05).ConclusionPatients with lung or breast cancer receiving MEC or HEC had significantly lower risk of CINV events associated with hospital/ED admissions if initiated and maintained on palonosetron relative to patients receiving 5-HT3 RA regimens.

Chemotherapy-induced nausea and vomiting and antiemetic prophylaxis with palonosetron versus other 5-HT3 receptor antagonists in patients with cancer treated with low emetogenic chemotherapy in a hospital outpatient setting in the United States

Abstract Background: The incidence of overall (acute and delayed) chemotherapy-induced nausea and vomiting (CINV) events among patients treated with single- and multi-day low emetogenic chemotherapy (LEC) is not well established. We studied a cohort of patients receiving LEC and antiemetic prophylaxis with palonosetron (Group 1) versus other 5-HT3 receptor antagonists (5-HT3-RAs) (Group 2), to determine the overall rate of CINV and the proportion of patients experiencing delayed CINV (days 2–7 of a CT cycle) in a hospital outpatient setting. Methods: Patients aged ≥18 years with cancer diagnosis initiating single-day and multi-day LEC for the first time between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective database. CINV events (ICD-9-CM codes for nausea, vomiting, or volume depletion or CINV-related rescue medications) were assessed descriptively. A generalized linear multivariate regression model was developed, estimating the overall CINV event rate among Group 1 and 2 patients in the follow-up period (first of eight chemotherapy [CT] cycles or 6 months). Results: In the follow-up period, out of a total of 10,137 overall CINV events (single-day and multi-day LEC), 8783 events (86.6%) were identified in single-day LEC treated patients. Within single-day LEC treated events, in the first cycle, of 3184 events, 2996 (94.1%) events were delayed. Average number of delayed events per patient remained consistent throughout the eight cycles (3.1 [1st cycle] vs. 2.9 [8th cycle]; P = 0.842]). Among 2439 patients on antiemetic prophylaxis with a 5-HT3-RA, 10.1% (n = 247) initiated palonosetron. Regression analysis indicated that Group 1 patients (versus Group 2) had a 15.2% reduction in CINV event rate per CT cycle; P = 0.0403. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship. Conclusion: In this retrospective analysis, delayed CINV comprised a major proportion of overall CINV among cancer diagnosed patients on single-day LEC. Additionally, palonosetron prophylaxis was associated with a significantly lower overall CINV event rate versus other 5-HT3-RA prophylaxis in single- and multi-day LEC treatment.

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis.

BACKGROUND No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, 7particularly delayed nausea. OBJECTIVES To compare the effcacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea. METHODS Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively. RESULTS Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs. LIMITATIONS This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be infuenced by interindividual variability. CONCLUSION Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable tolerability. DISCLOSURES AND FUNDING Dr Schwartzberg is a consultant to and Dr Cox an employee at Esai. Mr Ballinari is a member of staff at and Dr Thorn consults for Helsinn Healthcare SA. Funding to support this study and the preparation of this manuscript was provided by Eisai Inc.

Abstract P3-09-09: Eribulin mesylate plus capecitabine for adjuvant treatment in post-menopausal ER+ early-stage breast cancer: A phase 2, multicenter, open-label study using 2 different dosage regimens

Introduction: Eribulin mesylate is a novel non-taxane microtubule inhibitor. The primary objective of this study was to explore feasibility of administering eribulin plus capecitabine as adjuvant therapy in subjects with early-stage, estrogen receptor-positive (ER+) breast cancer. Methods: In this phase 2, open-label, multicenter study, 67 postmenopausal women with early HER2-normal/HER2-negative, ER+ breast cancer received four 21-day cycles of treatment with eribulin mesylate (1.4 mg/m 2 IV on day 1 and day 8 of each cycle) in combination with capecitabine (900 mg/m 2 orally twice daily on days 1 through 14 of each cycle). A second dosage regimen for capecitabine was initiated after dose reductions and treatment discontinuations were noted and attributed to capecitabine-related toxicities, such as grade 3/4 GI events and hand-foot syndrome. As a consequence, capecitabine was administered to an additional cohort of 10 subjects at a fixed dose of 1500 mg given orally twice daily on a 7 days on/7 days off schedule for the 4 cycles; eribulin mesylate was administered on the same dosage schedule as the original regimen (1.4 mg/m 2 IV on day 1 and day 8 of each cycle). The 7 days on/7 days off regimen for capecitabine was based on mathematical modeling and has been shown to have an acceptable toxicity profile, including minimal gastrointestinal toxicity, when given in combination with bevacizumab to patients with metastatic breast cancer. Feasibility was assessed based on relative dose intensity (RDI) of the combination using prespecified criteria of 80% of subjects achieving an RDI of at least 85% of the regimen with lower 95% confidence boundary >70%; safety and tolerability were also assessed. Results: Among subjects on the original eribulin plus capecitabine dosing schedule (n=64), the average (SD) RDI was 90.6% (11.94%) and the feasibility rate was 81.3% (95% lower CI: 71.4%), indicating that this dosage regimen is feasible. Dose reductions, missed doses, and withdrawals due to adverse events were ascribed more to capecitabine (36%, 85%, and 18%, respectively) than to eribulin (21%, 8%, and 12%, respectively), which led to higher RDI and feasibility rates for eribulin (93.5% and 82.8%, respectively) than for capecitabine (87.8% and 71.9%). Grade 3/4 hand-foot syndrome ascribed to capecitabine only, led to dose reductions in 11.9% of subjects under the original dosing schedule. The most common adverse events under the original dosing schedule were alopecia (77.6%), fatigue (58.2%), and nausea (52.2%). With the new dosing schedule (n=9), higher RDI and feasibility rates were achieved, the average RDI was 96% and the feasibility rate was 100%, indicating that this alternative regimen is also feasible, and probably better. (Detailed feasibility and safety data with new dosing regimen will be available at the time of the presentation.) Conclusions: Adjuvant use of the combination of eribulin plus capecitabine is feasible in patients with early, HER2-normal/HER2-negative, ER+ breast cancer. The combination had an acceptable safety profile under the original dosing schedule and has the potential to be improved by use of a 7 day on/7 day off regimen of capecitabine. Citation Format: John W Smith II, Svetislava Vukelja, Anthony Hoffman, Vicky Jones, Kristi McIntyre, Erhan Berrak, Angela Teng, David Cox, Joyce O9Shaughnessy. Eribulin mesylate plus capecitabine for adjuvant treatment in post-menopausal ER+ early-stage breast cancer: A phase 2, multicenter, open-label study using 2 different dosage regimens [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 P3-09-09.

Abstract P5-17-02: Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC

Introduction: Eribulin mesylate is a nontaxane microtubule inhibitor approved to treat MBC in patients (pts) who previously received ≥2 chemotherapeutic regimens for MBC. A phase 2 study of first-line eribulin for HER2-negative (HER2-) MBC showed an overall response rate of 29%, median 6.8 m progression-free survival, and tolerability consistent with earlier studies. We present prespecified quality of life (QoL) results for this trial. Methods: Pts (N=56) received eribulin mesylate 1.4 mg/m 2 IV on days 1 and 8 of each 3-wk cycle (median: 7 cycles). QoL was assessed using the EORTC QoL assessment (QLQ-C30) and a breast-cancer specific questionnaire (QLQ-BR23) pretreatment (baseline) and on day 1 of every other cycle during treatment. Percentage of pts with at least ±10-point change from baseline was summarized descriptively. Linear mixed-effects models were used to evaluate changes over time and compare responders vs nonresponders controlling for baseline score and time effect. Time-to-event analysis was performed on time to deterioration, defined as time from 1st dose to 1st occurrence of worsening in QoL score that reached minimally clinically important difference (MID; eg, 10 points in global health status in QLQ-C30) from baseline without further improvement of at least MID. Results: For QLQ-C30 at cycle 6 (n=29), more pts had at least a 10-point improvement from baseline in role, emotional, and social functioning; fatigue, nausea/vomiting, pain, dyspnea, and insomnia item scores, than had worsening. More pts had worsening in global health status/QoL, cognitive functioning, and diarrhea (Table). Median time to deterioration in global health status/QoL was 5.06 m (responders, 8.54 m; nonresponders, 3.71 m; hazard ratio=0.60, P=0.22). In linear mixed models, responders (n=16) performed better than nonresponders (n=40) in role functioning (P=0.011), emotional functioning (P=0.031), fatigue (P=0.007), pain (P=0.047), insomnia (P=0.018), and appetite loss (P=0.032). Mean symptom scores were significantly correlated with corresponding adverse event rates for nausea and vomiting, dyspnea, appetite loss, constipation, and diarrhea; Spearman rank correlation coefficients ranged from 0.31 to 0.54. For QLQ-BR23 at cycle 6, symptom scores were mostly stable; more pts had worsening in body image and systemic therapy side effects than had improvement and more pts had improvement in breast and arm symptoms than had worsening. Responders also had longer time to symptom deterioration. Conclusions: In this study of first-line eribulin treatment for HER2- MBC, a majority of pts had stable or improvement in QoL scales. Responders to eribulin were more likely than nonresponders to have stable or improved QoL. Citation Format: Lee Schwartzberg, Kristi McIntyre, Joyce O9Shaughnessy, Stefan Gluck, Erhan Berrak, James Song, David Cox, Linda Vahdat. Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC [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 P5-17-02.

Abstract P5-17-03: Quality of life results from a phase 2, multicenter, single-arm study of eribulin mesylate plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer

Introduction: Eribulin mesylate is a nontaxane microtubule dynamics inhibitor that has showed an overall survival benefit relative to other commonly used agents in patients with ≥2 prior MBC therapies. Primary data from a phase 2 trial for first-line eribulin + trastuzumab [TRAS] in HER2+ patients with MBC showed an objective response rate of 71%, clinical benefit rate of 84.6%, disease control rate of 96.2%, PFS of 11.6 months, and tolerability similar to known profiles for these agents. Here, we present prespecified QoL, efficacy, and safety/tolerability results. Methods: Patients received eribulin mesylate 1.4 mg/m 2 IV on days 1 and 8 of each 21-day cycle and initial TRAS (8 mg/kg IV/day 1), followed by 6 mg/kg on day 1 of each subsequent cycle. Response, PFS, QoL as measured by EORTC QoL assessment tool (QLQ-C30) and QLQ-BR23, and tolerability were assessed. Percentage of patients with at least ±10-point change from baseline was calculated at each visit. Time to deterioration was defined as time from first dose to worsening in QoL score that reached minimally clinically important difference (MID) (ie, 10 points in global health status [GHS] in QLQ-C30) without further improvement of at least MID; this was estimated overall and by response status. Results: At cycle 6 (n=44; completion rate=84.6% of 52 patients enrolled), more patients fell in the stable category (within +/-10 points change from baseline), except for pain (47.7% with improvement), cognitive functioning (45.5% worsening), fatigue and systemic therapy side effects (50% worsening for each), and arm symptoms (47.7% improvement) (Table). Median times to deterioration for GHS/QoL were 7.6 months overall (n=51), and 7.6 and 7.0 months for responders (n=36) and nonresponders (n=15), respectively (HR 0.73; 95% CI 0.32, 1.68; P=0.446). Mean symptom scores in EORTC QLQ-C30 were significantly correlated with corresponding AE rates for fatigue (r=0.31), nausea/vomiting (r=0.50), pain (r=0.41), dyspnea (r=0.49), insomnia (r=0.35), constipation (r=0.30), and diarrhea (0.40; P≤0.03 for all comparisons). The most common treatment-related AEs (all grade incidence ≥25%) were alopecia (88.5%), fatigue (69.2%), peripheral neuropathy (69.2%), neutropenia (59.6%), nausea (46.2%), diarrhea (32.7%), anemia (25%), constipation (25%), and decreased appetite (25%). Conclusions: Given the improvements in pain and in arm and breast symptoms, long median time to deterioration in functioning/symptom scales in this analysis, and the tumor response rates and safety profile in the primary analysis, combination eribulin/TRAS may be an acceptable treatment option for locally recurrent or HER2+ MBC and merits further study in larger clinical trials. Citation Format: Lee Schwartzberg, Sharon Wilks, Shannon Puhalla, Joyce O9Shaughnessy, Erhan Berrak, James Song, David Cox, Linda Vahdat. Quality of life results from a phase 2, multicenter, single-arm study of eribulin mesylate plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer [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 P5-17-03.