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Purpose To provide evidence-based guidance on the optimum management of chronic pain in adult cancer survivors. Methods An ASCO-convened expert panel conducted a systematic literature search of studies investigating chronic pain management in cancer survivors. Outcomes of interest included symptom relief, pain intensity, quality of life, functional outcomes, adverse events, misuse or diversion, and risk assessment or mitigation. Results A total of 63 studies met eligibility criteria and compose the evidentiary basis for the recommendations. Studies tended to be heterogeneous in terms of quality, size, and populations. Primary outcomes also varied across the studies, and in most cases, were not directly comparable because of different outcomes, measurements, and instruments used at different time points. Because of a paucity of high-quality evidence, many recommendations are based on expert consensus. Recommendations Clinicians should screen for pain at each encounter. Recurrent disease, second malignancy, or late-onset treatment effects in any patient who reports new-onset pain should be evaluated, treated, and monitored. Clinicians should determine the need for other health professionals to provide comprehensive pain management care in patients with complex needs. Systemic nonopioid analgesics and adjuvant analgesics may be prescribed to relieve chronic pain and/or to improve function. Clinicians may prescribe a trial of opioids in carefully selected patients with cancer who do not respond to more conservative management and who continue to experience distress or functional impairment. Risks of adverse effects of opioids should be assessed. Clinicians should clearly understand terminology such as tolerance, dependence, abuse, and addiction as it relates to the use of opioids and should incorporate universal precautions to minimize abuse, addiction, and adverse consequences. Additional information is available at www.asco.org/chronic-pain-guideline and www.asco.org/guidelineswiki .

Purpose Trastuzumab emtansine (T-DM1), an antibody–drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) ≥ 55% received (neo)adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety. Results Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (≥ 10 percentage points from baseline to LVEF < 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received ≥ one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed ≥ 95% of the planned radiation dose with delay ≤ 5 days. Conclusion Use of T-DM1 for approximately 1 year after anthracycline-based chemotherapy was feasible and generally well tolerated by patients with HER2-positive EBC, providing support for phase III trials of T-DM1 in this setting.

10034Background: Breast cancer incidence increases with age, but older patients tend to be underrepresented in clinical trials. To address this underrepresentation, this study examined the role of ...

Purpose Older node-positive patients treated with newer adjuvant chemotherapy regimens have improvements in relapse-free and overall survival similar to younger patients. We compared toxicity of older and younger patients in three randomized trials of adjuvant chemotherapy. Patients and Methods Toxicity data were available for 93% of 6,642 patients enrolled. The three trials included: Cancer and Leukemia Group B (CALGB) 8541, a comparison of cyclophosphamide, doxorubicin, and fluorouracil in three dose schedules; CALGB 9344: cyclophosphamide and doxorubicin with or without paclitaxel; and CALGB 9741: cyclophosphamide, doxorubicin, and paclitaxel every 2 versus every 3 weeks. National Cancer Institute grade 3 to 5 toxicities were compared among age groups. Results Seven percent of patients (n = 458) were age 65 or older, 3% were 70 or older, 38% were 51 to 64, and 55% were 50 or younger. Twenty-four deaths (0.4%) were attributed to treatment; seven (1.5%) of 486 in patients 65 or older, 10 (0.40%) of 2,480 in patients who were 51 to 64 years, and seven (0.19%) of 3,676 occurred in patients younger than 50. In multivariate analysis, older patients were significantly more likely to have grade 4 hematologic toxicity, to have discontinued treatment for toxicity, or to have died of acute myeloid leukemia/myelodysplastic syndrome. There were no significant differences in grade 3 to 4 nonhematologic toxicity. Conclusion Healthy older patients who met the strict eligibility criteria for these trials had a higher rate of hematologic toxicity and treatment-related deaths than younger patients, but no increase in nonhematologic toxicity. Elderly patients treated with newer adjuvant chemotherapy regimens derive the same benefits from newer chemotherapy regimens as younger patients but should be cautioned about the increased risk of toxicity and treatment-related death.

Purpose: Using a 2 × 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node–positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. Patients and Methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A × 4 (doses) → T × 4 → C × 4 with doses every 3 weeks, (II) sequential A × 4 → T × 4 → C × 4 every 2 weeks with filgrastim, (III) concurrent AC × 4 → T × 4 every 3 weeks, or (IV) concurrent AC × 4 → T × 4 every 2 weeks with filgrastim. Results: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P = .010), and OS (RR = 0.69; P = .013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Conclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.

PURPOSE This study compared the clinical efficacy of oxycodone hydrochloride controlled-release (CR) tablets administered every 12 hours with immediate-release (IR) oxycodone tablets administered four times daily in patients with cancer-related pain. PATIENTS AND METHODS Cancer patients who required therapy for moderate to severe pain were randomized to CR oxycodone every 12 hours (n=81) or IR oxycodone four times daily (n=83) for 5 days in a multicenter, double-blind study. Pain intensity was assessed four times daily (categorical scale of none, slight, moderate, and severe); acceptability of therapy was assessed twice daily (categorical scale of very poor, poor, fair, good, and excellent). RESULTS Pain intensity remained slight during the study, with mean oxycodone doses of 114 mg/d (range, 20 to 400 mg/d) for CR and 127 mg/d (range, 40 to 640 mg/d) for IR. Acceptability of therapy was fair to good with both treatments. While standard conversion ratios provided an acceptable dose for many patients, a protocol amendment that allowed initial titration and use of rescue medication reduced the discontinuation rate for lack of acceptable pain control (from 34% to 4% with CR and from 31% to 19% with IR before and after amendment, respectively) without increasing the discontinuation rate for adverse events (from 8% to 7% with CR and from 13% to 11% with IR). Fewer adverse events were reported with CR (109) than with IR (186) oxycodone (P=.006). CONCLUSION CR oxycodone every 12 hours was as effective as IR oxycodone four times daily in managing moderate to severe cancer-related pain and was associated with fewer reports of adverse events.

97 Background: Research on the psychological status of medical oncologists (MO) is limited. The Make Your Dialogue Count survey explored emotional experiences of licensed US MOs who treat ≥ 5 women with MBC/month as well as women ( ≥ 21 y) with MBC. Methods: A survey was conducted (June-Aug 2014) online, by paper and telephone; MOs responded online only. Patient (pt) data were unweighted. MO data were weighted by geographic region and years in practice by sex to match actual proportions in the population. Statistically significant differences between groups were determined by standard t-test of column proportions and means at the 95% confidence level (marked by *). Results: 359 pts (median age 53 y) and 252 MOs (median age 49 y; median 15 y in practice) completed surveys. At initial MBC diagnosis, more MOs than pts felt that showing care and compassion (81% vs 72%) and helping pts cope with the diagnosis (63% vs 51%) were very important, and fewer felt that referring pts to support services (24% vs 38%) was very important. More MOs practicing < 15 y vs ≥ 15 y said it was very important to refer pts to support services at first diagnosis (30% vs 19%*). Slightly more MOs with more experience perceived emotions like anxiety, commitment, hopefulness, and determination in their pts at initial diagnosis. Many MOs (42%) reported that treating women with MBC had a lot/a great deal of negative emotional impact; 81% strongly/somewhat agreed that it is unprofessional to let emotions impact treatment recommendations; and 23% reported that emotions kept them from providing some information to pts. Less experienced MOs said their emotions kept them from providing some information to their pts than their more experienced counterparts (29% vs 17%*). Most MOs (93%) did not want to give their pts false hope; yet 27% reported that in certain situations, they do not discuss with pts that MBC is incurable. Conclusions: MOs empathize with pts and feel responsible for providing them emotional/psychological support. MOs revealed the negative emotional weight of their work. MOs with less experience were more impacted by their emotions than MOs with more experience. Acknowledging MOs’ emotions is important and underscores their own need for psychological/emotional support.

e20575 Background: About 5% of newly diagnosed BC cases in the US are metastatic, and up to 30% of women diagnosed with early-stage BC later develop MBC. The Make Your Dialogue Count survey probed ...

124 Background: About 232,670 cases of breast cancer will be diagnosed in the US in 2014, of which 86,088 (37%) will be metastatic advanced breast cancer (ABC). The 2013 Global Count Us, Know Us, Join Us survey found that 53% of US women with ABC wanted more time to discuss their needs during clinic visits, and 60% believe their cancer treatment options are limited. To better understand unmet patient needs and potential communication gaps with physicians, surveys were developed for women with ABC, their caregivers, and oncologists. The oncologists’ survey results are presented. Methods: The Make Your Dialogue Count survey for oncologists has 32 items. Responses are single or multiple response numeric text or rated on a 4-point Likert scale. Harris Poll conducted this online survey from June through July 2014 among randomly selected, licensed US medical oncologists who treat ≥ 5 women with ABC per month. Responses for geographic region and number of years in practice by sex were weighted to match actual proportions in the population. Results: By July 15, 2014, 228 oncologists responded. At initial diagnosis, showing care and compassion was very important to 79% of oncologists; helping patients cope with diagnosis (62%) and manage cancer symptoms (56%) and discussing expected treatment response (57%) and side effects (51%) were also very important. Most oncologists (88%) revealed that treating women with ABC has a negative emotional toll. Although 81% of oncologists believe it to be unprofessional to let their emotion affect treatment recommendations, 26% reported that their emotions kept them from providing some information. Notably, 31% of oncologists reported that in certain situations, they have not discussed with patients that ABC is incurable. Conclusions: Caring for terminally ill patients has an emotional impact on oncologists. For some, their emotions have influenced what treatments they recommend and what information they impart. Our findings show that oncologists are compassionate and share disease- and treatment-related information and highlight the need to develop communication strategies that facilitate exchange between oncologists and their patients with ABC.

1032 Background: Obesity is a predictor of poor outcomes in women with early-stage breast cancer (BC). Some reports suggest that obesity is associated with aggressive tumor histology. We examined the relationship between BMI at diagnosis and PAM50 subtype, and explored the interaction between BMI and subtype on prognosis in early BC. Methods: CALGB 9741 evaluated dose-density and sequence in node-positive BC. All patients received doxorubicin, cyclophosphamide and paclitaxel dosed by actual body weight without cap or dose adjustment. The primary endpoint was RFS. Height and weight at diagnosis were abstracted from patient records; the PAM50 assay was performed using the Nanostring platform. Association between PAM50 and BMI was assessed by a chi-squared test. The prognostic value of BMI conditional on PAM50 was tested as a continuous variable using Cox models for RFS adjusted for number of involved nodes, tumor size, menopausal status, drug sequence, and dose density. Results: Baseline height and weight were available for 1909 of 2005 enrolled patients; 1272 also had subtype determination by PAM50. Distribution of subtypes differed significantly by BMI (p=0.03), with all weight groups having similar proportions of Basal and HER-2 Enriched subtypes and with obese patients having lower rates of Luminal A (30 vs 35%) and higher rates of Luminal B (39 vs 26%) tumors as compared to normal-weight individuals. In multivariate analyses, BMI and subtype were independent predictors of RFS (p=0.011 and p

532 Background: T-DM1 has demonstrated clinical activity as a single agent in patients (pts) with previously untreated MBC. In a previous phase II randomized trial of T-DM1 vs trastuzumab + docetaxel, T-DM1 had no clinically significant cardiac events, no cases of post-baseline left ventricular ejection fraction (LVEF) ≤40%, and fewer grade ≥3 adverse events (AEs; Hurvitz, ESMO 2011). This phase II study assessed the clinical safety and feasibility of T-DM1 following anthracycline-based chemotherapy in the adjuvant or neoadjuvant setting for early-stage HER2-positive breast cancer. Methods: TDM4874g (NCT01196052) is a phase II single-arm, open-label study of T-DM1 (3.6 mg/kg q3w IV; up to 17 cycles) following completion of doxorubicin/cyclophosphamide (AC; q2w or q3w for 4 cycles), or 5-fluorouracil/epirubicin (100 mg/m2)/cyclophosphamide (FEC; q3w for 3-4 cycles) chemotherapy in pts with early-stage HER2-positive breast cancer. Pre-chemotherapy LVEF by MUGA/ECHO ≥55% was required for enrollment. Co-primary endpoints are safety and rate of pre-specified cardiac events following initiation of T-DM1 treatment. An interim analysis was planned for the first 60 pts evaluable for cardiac safety (received ≥1 T-DM1 dose). Results: For pts in the interim analysis (20 received AC, 40 FEC), the most common all-grade T-DM1-related AEs were nausea (n=20), asthenia (n=17), and headache (n=17); 8 pts had grade 3/4 T-DM1-related AEs (including 3 with grade 3 increased aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]). No deaths occurred. Two pts had AEs leading to T-DM1 discontinuation (grade 3 AST and grade 2 ALT increase; grade 3 thrombocytopenia). No pre-specified cardiac events occurred; no pts delayed or discontinued T-DM1 due to cardiac AEs; there were no reports of grade ≥2 left ventricular systolic dysfunction, heart failure, or LVEF

559 Background: Recent data show older pts derive the same relapse-free and survival benefits as younger pts when treated with newer more intense adjuvant ADJ Cx regimens (Jama 293:1073, 2005). We now compare toxicity of older and younger pts treated in 3 CALGB ADJ trials that used recently developed, intensive Cx regimens including anthracyclines and paclitaxel (T). Methods: Toxicity data were available for 6174 of 6642 pts (93%) enrolled in 3 CALGB/CTSU randomized clinical trials for N+ BC [8541: comparison of CAF in 3 dose schedules; 9344: AC ± T; 9741: ATC dose-dense vs q3 weeks]. Grade (G) 3–5 (NCI criteria) toxicities were compared by age at enrollment ( [Table: see text] [Table: see text]

620 Background: C9741 demonstrated superior DFS and OS for q14 day A, T, and C compared to q21 day treatment and no difference in outcomes with concurrent vs. sequential A and C. (J Clin Oncol 21:1431–39. 2003) Study design: Arm S3: Ax4 ->Tx4->Cx4 q3 weeks; Arm S2 (DD): Ax4->Tx4->Cx4 q2 weeks with filgrastim; Arm C3: ACx4->Tx4 q3 weeks; Arm C2 (DD): ACx4->Tx4 q2 weeks with filgrastim; A=doxorubicin 60mg/m2, T=paclitaxel 175 mg/m2 over 3 hours, and C=cyclophosphamide 600mg/m2. Red cell transfusion was observed in 13% of the first 412 patients (3,973 treatment cycles) with C2, compared to less than 4% in S2 and C3, and zero in S3. This observation prompted a more detailed review of the toxicity data. Methods: We performed a retrospective review of hemoglobin per course, use of epoetin alpha and transfusions. Use of epoetin alpha and transfusions were at discretion of physician. Time-to-event distributions were estimated by the Kaplan-Meier technique; two or more such distributions were compared with the log...