Dueck, Amylou C.

6587 Background: Recently the Patient-Reported Outcomes version of the CTCAE was developed to augment clinically graded adverse events with information reported directly by patients on clinical trials (Basch, 2009). The validation and potential application of PRO-CTCAE in phase I clinical trials are of great interest as toxicity is the primary endpoint. Methods: Selected PRO-CTCAE items (21 items measuring 12 symptomatic adverse events) corresponding to the major adverse events required to be graded clinically were collected in an ongoing phase I clinical trial of weekly cilengitide and paclitaxel in patients with advanced solid malignancies (NCT01276496). PRO-CTCAE was administered in a paper booklet by a clinical research associate prior to treatment on days 1, 8 and 15 of their regular visits. These PRO-CTCAE items were summarized descriptively in comparison to clinician-assessed CTCAE ver 4.0 (NCI, 2009) during the first cycle. As a pilot study to assess feasibility of PRO-CTCAE in phase I trials, PRO-CTCAE was not intended for determination of dose-limiting toxicity. Results: Twelve patients were accrued to two separate doses of cilengitide and paclitaxel. The median age was 56 (range 36—67) and half of patients were female. All patients had an ECOG performance score <= 1. Over 90% of patients had received prior surgery and chemotherapy. All but one patient completed weekly PRO-CTCAE during the first cycle, the only patient refused to complete weeks 2 and 3 did not give a reason. PRO-CTCAE captured most of the symptomatic adverse events reflected in clinician-assessed CTCAE. Some symptomatic adverse events were not reported clinically by CTCAE but were reported by patients by PRO-CTCAE. Overall, PRO-CTCAE items indicated slightly more severe degree of symptoms experienced by patients than those reported in CTCAE. Conclusions: This is the first study that PRO-CTCAE items were integrated within regular study visits in a phase I trial. The administration of PRO-CTCAE has been proved feasible and fruitful, providing consistent and enhanced symptomatic toxicity from the patient point of view. The addition of PRO-CTCAE did not significantly increase patient burden. Clinical trial information: NCT01276496.

e16065 Background: Estrogens, in addition to androgen may contribute to the progression of prostate cancer.The combination of bicalutamide, a non-steroidal anti-androgen, and raloxifene, a selective estrogen receptor modulator, has a synergistic effect on cell death of prostate cancer cell lines such as DU145 and PC3. We investigated the safety of combined treatment of bicalutamide and raloxifene on quality of life in patients affected by hormone-resistant prostate cancer. Methods: Eligibility requirements included metastatic hormone-resistant prostate cancer, Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received the combination of bicalutamide, 50 mg, and raloxifene, 60 mg, daily in 28 day cycles for a maximum of 6 cycles. The primary endpoint was to describe the adverse event profile of combined treatment with bicalutamide and raloxifene. The secondary endpoint was to describe the quality of life of patients receiving the combination. Adverse events were graded by the investigator using the NCI Common Terminology Criteria for Adverse Events version 4.0 and the quality of life was assessed by the patient using aLinear Analog Scale Assessment (scale of 0-100). Serum levels of estradiol and testosterone were monitored during treatment. Results: Eighteen evaluable patients were included in the statistical analysis after an initial run-in safety cohort of six patients. Two patients completed 6 cycles per protocol, the remaining sixteen patients were taken off protocol after disease progression. Patients completed a median of 2 cycles. There were no grade 4 events and grade 3 adverse events consisted of hypertension (5.6%) and back pain (5.6%). Erectile dysfunction (grade 1) was the most common adverse event (77.8%). Patient assessment of quality of life (mental, physical, social, emotional, spiritual) did not reveal any statistically different changes after 2 cycles of treatment. An analysis of testosterone and estradiol levels will be reported. Conclusions: We conclude that combination of bicalutamide and raloxifene is well-tolerated. The combination of androgen and estrogen receptor blockade warrants further study for efficacy in hormone-resistant prostate cancer. Clinical trial information: NCT01050842.

520 Background: There is considerable interest in developing HER2 testing criteria for adjuvant H. We used the 21-gene assay to examine the relationship of HER2 mRNA to benefit from H. Methods: N9831 compared adjuvant chemotherapy AC-T to concurrent chemotherapy-trastuzumab AC-TH in stage I-III HER2+ breast cancer. Recurrence Score (RS) and HER2 mRNA expression were determined by Oncotype DX (neg<10.7, equiv 10.7 to <11.5, and pos ≥11.5 log2 expression units). Cox regression was used to assess the association of HER2 expression with H benefit for distant recurrence. Results: Median follow-up: 7.4 yrs. Of 1,940 total pts, 901 had consent and sufficient tissue. HER2 by RT-PCR was neg in 130 (14%), equiv in 85 (9%), and pos in 686 (76%) pts. Concordance between HER2 assessments was 95% for RT-PCR vs central IHC (>10% + cells = +), 91% for RT-PCR vs central FISH (≥2.0 = pos) and 94% for central IHC vs central FISH. In the primary analysis, the association of HER2 expression with H benefit was marginally non-significant (P=0.057). In hormone receptor pos pts (local IHC) the association was significant (P=0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 mRNA expression levels. The observed treatment benefit in low HER2 pts was not due to imbalance between arms in RS and individual gene expression values. Conclusions: Concordance among HER2 assessments by central IHC, FISH, and RT-PCR was high. Association of HER2 mRNA expression with H benefit was marginally non-significant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in the pts with either IHC+ or FISH+ tumors. Benefit was observed in pts with high HER2 by RT-PCR but also observed for the small groups of pts with negative results by quantitative RT-PCR or FISH (Table). Plausible mechanisms for this observation will be discussed. [Table: see text]

9047 Background: Symptomatic adverse events (AE) in cancer trials are reported by clinicians using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). To integrate the patient perspective into AE reporting, NCI contracted (HHSN261201000043C) to create a patient-reported outcomes companion tool (PRO-CTCAE). We report the validity and reliability of PRO-CTCAE’s 124 items reflecting 78 symptomatic AEs. Methods: English-speaking subjects (n=869; 44% male; median [mdn] age 59; 32% racial/ethnic minority; 34% high school or less; 17% ECOG Performance Status [PS] 2-4) receiving treatment for a range of cancers at 4 NCI-designated cancer centers and 5 sites in NCI's Community Cancer Centers Program completed a web-based survey in clinic including PRO-CTCAE and EORTC QLQ-C30. Pearson correlations were computed between PRO-CTCAE items and QLQ-C30 scales. Differences in PRO-CTCAE item scores between clinician-reported ECOG PS (0-1 vs 2-4) groups were computed. Test-retest reliability of 48 prespecified items was evaluated in a subset (n=79). Results: Correlations in the expected direction were observed for 116/124 PRO-CTCAE items with the QLQ-C30 global health scale (mdn r=-.21; range .08 to -.57). Stronger correlations were seen for PRO-CTCAE items with conceptually related QLQ-C30 domains: fatigue with physical, role and social functioning (-.54 to -.66); anxiety and depression with emotional functioning (-.54 to -.70); and concentration and memory problems with cognitive functioning (-.62 to -.72) [all p <0.001]. Fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea items strongly correlated with corresponding QLQ-C30 symptom scales (.69 to .79, all p <0.001). Scores for 98/124 PRO-CTCAE items were higher in the ECOG PS 2-4 vs 0-1 group (mdn effect size .3). Test-retest reliability was observed across all tested items (mdn intraclass correlation coeff .77; range .53 to .96). Conclusions: Results demonstrate favorable validity and reliability of PRO-CTCAE in a large, heterogeneous sample of patients undergoing cancer treatment. Further testing in multicenter treatment trials is underway.

8053 Background: Lenalidomide (LEN) is an immunomodulatory agent that has shown significant single-agent anti-lymphoma activity in patients with relapsed disease and in combination may enhance the efficacy of rituximab by various mechanisms. There is limited data on the role of LEN in combination regimens for treatment-naïve patients. This phase II single arm trial was designed to evaluate tumor response, toxicity (AE) and survival with a combination of LEN, rituximab, cyclophosphamide (CTX) and dexamethasone (DEX) (LR-CD) in symptomatic untreated patients with low grade B-cell non-Hodgkin lymphoma. Methods: Eligibility required age ≥18, ECOG PS ≤2, confirmed diagnosis of low-grade B-cell lymphoma (FL1-2, SLL, MZL or LPL/WM), measurable nodes ≥2cm or IgM ≥400mg/dL(LPL/WM), ANC ≥1400/mm3, platelets ≥100,000/mm3, creatinine ≤2mg/dL, signed informed consent and in need of therapy. Treatment consisted of IV rituximab 375mg/m2 D1, oral LEN 20mg D1-21, CTX 250mg/m2 D1, 8, 15, DEX 40mg D1, 8, 15, 22 and ASA 325 mg daily in a 28 day cycle. Treatment continued 2 cycles beyond best response (max 12). Toxicity was assessed by NCI CTCAE v3.0. Results: 28 patients have enrolled at Mayo Clinic with 25 evaluable for toxicity and 21 for response: Median age 65(43-83), 72% male, FL 24%, MZL 28%, LPL/WM 38%, and SLL 4%. Median number of cycles given was 5. Overall response in 21 patients with response data is 95% (95% CI 76-100%) with 19% CR (95% CI 5-42%), and 76% PR (confirmed and unconfirmed, 95% CI 53-92%). The ORR in 8 patients with LPL/WM with response data was 88%, all PR (95% CI 47-100%). At a median f/u of 14.7 months 96% are alive without progression. 1 death (unrelated) occurred 7.7 months after completing 12 cycles of treatment. The most common grade ≥3 AEs were neutropenia (37.5%), leukopenia (16.7%), anemia (12.5%) and fatigue (12.5%). Conclusions: The combination LR-CD with the novel agent LEN is feasible, well tolerated and produces high response rates in symptomatic patients with low grade B-cell NHL. Toxicities are manageable and similar to reported data of single agent LEN.

8010 Background: Carfilzomib is a proteasome inhibitor that irreversibly binds its target with favorable toxicity profile that has shown significant activity in relapsed multiple myeloma (MM). Here we used carfilzomib as the center of a 4 drug induction regimen designed for MM patients pre stem cell transplant (SCT). Methods: We conducted a phase I safety run in 6 patients with no DLT observed before expanding to phase II. The phase II regimen is shown below. Treatment was for 4 cycles with expected SCT post induction. For the phase II portion of this trial, the primary endpoint is the proportion of patients who have ≥ very good partial response to treatment. All patients received herpes zoster prophylaxis and ASA daily. Results: Twenty seven patients were enrolled. Median age was 65 (range 27-74). ORR for evaluable patients (n=17) at phase II dosing is 100%: CR 35%, VGPR 48%, PR 18% after 4 cycles of CYCLONE. Grade 3 toxicity was reported in 52% of patients and 14% experienced a grade 4 toxicity. Grade 3/4 toxicities occurring in >5% of patients included fatigue, neutropenia, lymphopenia, thromboembolism, myopathy. Toxicities of any grade seen in >20% of patients included fatigue, constipation, lethargy, thrombocytopenia, somnolence, creatinine increased, malaise. Four patients (20%) developed grade 1 sensory neuropathy; no higher grade or painful neuropathy was evident. All patients are alive. All patients advancing to SCT successfully collected stem cells. One patient with t(4;14) disease who was not transplanted has progressed. 94% remain progression free. Conclusions: The 4 drug CYCLONE regimen has remarkable efficacy (83% ≥VGPR) and manageable toxicity in newly diagnosed patients with multiple myeloma. Especially notable was the low incidence of neuropathy and depth of response (CR 35%) after only 4 cycles. Given the relative lack of toxicity an extension of this regimen at higher doses of carfilzomib (20/45mg/m2) has been initiated. [Table: see text]

6133 Background: Patient (pt) trial experience may give insight to quality of life (QOL) factors affecting accrual, retention and outcome. While pts are vital to clinical trial success, we know little about their post-trial opinions. This trial examined pt opinion of their trial and treatment decision making (TDM). Methods: Pts enrolled on designated North Central Cancer Treatment Group (NCCTG) phase II or III treatment trials completed the TDM Control Preferences Scale at baseline and the Was It Worth It (WIWI) satisfaction assessment at the ends of cycle 1 and active protocol treatment. The primary endpoint was the proportion of pts reporting worthwhile participation. Fisher Exact tests compared pt opinion across subgroups. Results: As of 01/15/2012, 264 pts were enrolled on 25 protocols and treated at 79 sites. 86% of pts were in phase II studies and 89% had stage IV disease. At the end of cycle 1, pts felt the trial was worthwhile (74%), would do it again (85%), and would recommend it to others (82%). 85% of pts reported undiminished QOL and only 7% rated the trial worse than expected. End of treatment responses were similar. Satisfaction rates varied by tumor site (p=0.04). 11% of pts having tumor response rated the trial as not worthwhile, and 66% of pts with progressive disease rated it worthwhile (see table). Pts with concordant preferred and actual TDM roles rated participation higher than pts with discordant TDM roles (see table). Conclusions: Most pts endorsed their clinical trial experience. Contrary to popular beliefs, treatment outcome did not have an overwhelming impact on pt satisfaction, and was just one of many factors such as TDM role discordance. Assessing pt satisfaction will inform future study design that can potentially improve pt accrual and retention. [Table: see text]

6108 Background: This pilot study evaluated whether providing clinicians with patient(pt) QOL results and symptom management pathways linked to QOL domains at the time of clinical appointment would result in improvement in QOL and treatment (tx) satisfaction. The objective was to obtain preliminary effect size estimates and logistical evidence for design of a larger, definitive trial. Methods: Oncology pts receiving 5-7 weeks of radiotherapy (RT) electronically completed QOL assessments (LASA) at baseline and biweekly prior to seeing clinicians. Was It Worth It (WIWI) and Interpersonal Patient-Provider Relationship (IPPRS) were measured at tx end. Pt endpoints (pro-rated primary endpoint LASA area under the curve (AUC), LASA changes from baseline, and WIWI responses) and clinician endpoints (IPPRS) were compared between the control group (Phase 1: no QOL feedback) and the intervention group (Phase 2: QOL feedback) via Wilcoxon, Chi-square and Fisher Exact tests. There was 80% power to detect a 10 point difference in average AUC. Results: 148 pts enrolled (79 Phase 1, 69 Phase 2) from 11/28/2008 to 09/20/2011 (sites GI (27%), Lung (22%) and Head and Neck (52%)). 68% received RT and chemo. There were consistently moderate effect sizes observed but no statistically significant differences in any AUC nor end of tx change from baseline scores. 20% fewer pts in phase 2 reported clinical deficits in overall QOL (pain). In pts receiving 7 weeks of RT, end of tx average overall QOL, mental well-being (WB), physical WB and pain severity were significantly better in Phase 2 pts. WIWI results showed 76% found participation worthwhile, 95% would participate again, and 92% would recommend the study to others. No differences between groups were found in communication between clinicians and pts (IPPRS). Conclusions: Preliminary estimates indicate potentially clinically significant improvements of moderate effect size in mental and physical WB and pain severity when clinicians received QOL real time with symptom management pathways. Further study is warranted in larger trial setting.

Objectives Pancreatic resection is associated with postoperative morbidity and reduced quality of life (QoL). A systematic literature review was conducted to understand the patient-reported outcome measure (PROM) landscape in early-stage pancreatic cancer (PC). Methods Databases/registries (through January 24, 2019) and conference abstracts (2014–2017) were searched. Study quality was assessed using the Newcastle-Ottawa Scale/Cochrane risk-of-bias tool. Searches were for general (resectable PC, adjuvant/neoadjuvant, QoL) and supplemental studies (resectable PC, European Organisation for Research and Treatment of Cancer QoL Questionnaire [QLQ] – Pancreatic Cancer [PAN26]). Results Of 750 studies identified, 39 (general, 22; supplemental, 17) were eligible: 32 used QLQ Core 30 (C30) and/or QLQ-PAN26, and 15 used other PROMs. Baseline QLQ-C30 global health status/QoL scores in early-stage PC were similar to all-stage PC reference values but lower than all-stage–all-cancer values. The QoL declined after surgery, recovered to baseline in 3 to 6 months, and then generally stabilized. A minimally important difference (MID) of 10 was commonly used for QLQ-C30 but was not established for QLQ-PAN26. Conclusions In early-stage PC, QLQ-C30 and QLQ-PAN26 are the most commonly used PROMs. Baseline QLQ-C30 global health status/QoL scores suggested a high humanistic burden. Immediately after surgery, QoL declined but seemed stable over the longer term. The QLQ-C30 MID may elucidate the clinical impact of treatment on QoL; MID for QLQ-PAN26 needs to be established.

AbstractBackgroundBladder cancer (BC) patients with advanced disease have poor outcomes. The use of patient‐reported outcomes (PROs) could lead to improvements in symptom management and hence quality of life (QoL). The aim of this study is to report correlations between selected PROs and QoL and thus to present symptoms that influence QoL. Identification of these symptoms during treatment can lead to earlier symptom management and thus secure improvements in QoL.MethodsBC patients in chemo‐ or immunotherapy for locally advanced or metastatic disease reported weekly PROs for the duration of their treatment. The PROs included EORTC QLQ‐C30 and QLQ‐BLM30 and 45 selected PRO‐CTCAE items. Spearman's correlation analysis was performed for all PRO‐CTCAE items and QLQ‐C30 global QoL and subdomains.ResultsIn this study, 78 BC patients reported 724 questionnaires. Spearman's analysis showed significant correlations between almost all PRO‐CTCAE items and the expected domain of QoL. The PRO‐CTCAE items with the strongest correlations with QoL were anxiety (F, frequency item) and emotional function (rs = −0.603, P < .0001), concentration (S, severity item) and cognitive function (rs = −0.704, P < .0001), discouraged (F) and emotional function (rs = −0.659, P < .0001), fatigue (S) and role function (rs = −0.659, P < .0001) and sad (F) and emotional function (rs = −0.711, P < .0001). The weakest correlations were found for the PRO‐CTCAE items urinary frequency, incontinence and urge, all with variations in the direction and significance of the correlations.ConclusionsThis study delivers information on which PROs may influence QoL for patients in clinical trials or daily clinic. Psychological issues have a strong impact on QoL and should be dealt with during treatment to secure the best possible QoL for BC patients.