Search

Patients with multiple myeloma (MM) experience substantial cancer/treatment-related symptom burden during maintenance therapy. This is a phase II randomized, double-blinded, placebo-controlled clinical trial to examine the effect of minocycline for symptom reduction by its potential anti-inflammatory effect. Eligible MM patients for maintenance therapy were randomized to receive minocycline (100 mg twice daily) or placebo. The MD Anderson Symptom Inventory for MM (MDASI-MM) was used to assess multiple symptoms weekly during the trial. Clinician-rated toxicities and blood samples were prospectively collected. The effect size, area under the curve (AUC), and t tests were used to determine the symptom burden between treatment groups and identify the 5 most-severe MDASI-MM symptoms. The longitudinal analysis compared the changes in symptom severity and associated inflammatory markers between groups over time. Sixty-nine evaluable MM patients (33 from the intervention group and 36 from the placebo group) were included. No grade 3+ adverse events related to study medication were noted. The AUCs for the 5 worst MDASI-MM symptoms (fatigue, pain, disturbed sleep numbness/tingling, and drowsiness) were not significantly different between two arms. Regardless of group assignment, pain reduction was positively associated with decreased serum levels of soluble tumor necrosis factor-α receptors 1 and 2 during therapy (all P < 0.05). This pPhase II randomized study observed no statistically significant positive signal impact from minocycline on symptom reduction or inflammatory markers during maintenance therapy for MM, although using minocycline was feasible and had a low toxicity profile.

BACKGROUND While women diagnosed with breast cancer have increased survival when compared with other cancers, survivorship may include residual symptom burden from treatment and continuing endocrine therapies. OBJECTIVE The objective of this study was to identify subgroups of breast cancer survivors experiencing similar symptom severity. METHODS Participants were 498 women with breast cancer, not on active treatment. Symptom severity was self-reported using the MD Anderson Symptom Inventory. Target symptoms were included in a latent profile analysis. Factors related to subgroup membership and differences in quality of life (QOL) and functioning were explored using logistic regression. RESULTS Mean age was 60.11 (SD, 11.32) years, 86.1% were white, and 79.1% were receiving endocrine therapy. Target symptoms included fatigue (reported at ≥5 by 22.8% of women), sleep disturbance (24.8%), and trouble remembering (17.2%). Two subgroups were identified: low symptom severity (77.0% of women) and high (23.0%). Older women (odds ratio [OR], 0.971; 95% confidence interval [CI], 0.952-0.989) and employed women (OR, 0.621; 95% CI, 0404-0.956) were less likely to be in the high subgroup; women with poorer performance status (OR, 1.653; 95% CI, 1.188-2.299) were more likely to be in the high subgroup. Women in the high subgroup reported lower QOL (P = .000) and greater interference with functioning (P = .000). CONCLUSIONS Two subgroups of women with distinct symptom severity were identified. IMPLICATIONS FOR PRACTICE Identification of women at risk for high symptoms during survivorship may allow clinicians to intensify their approach to symptom management, thereby mitigating poor outcomes and impairments in QOL.

BackgroundCombining poly (ADP-ribose) polymerase (PARP) with phosphatidylinositol-3-kinase (PI3K) pathway inhibitors is supported by strong preclinical rationale. We sought to assess safety and determine a recommended phase 2 dose (RP2D) for PARP inhibitor olaparib combined with the AKT inhibitor, capivasertib, and evaluate molecular markers of response and resistance.MethodsAs part of a larger phase 1b trial, we performed a safety lead in of olaparib and capivasertib followed by expansion (n=24) in endometrial, triple negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300mg orally twice daily and capivasertib orally twice daily on a four day on three day off schedule was evaluated. Two dose levels (DL) were planned: capivasertib 400mg (DL1); capivasertib 320mg (DL-1). Patients underwent biopsies at baseline and after 28 days.Findings38 patients were enrolled. 7 (18%) patients had known germlineBRCA1/2mutations. The first two patients on DL1 experienced dose limiting toxicities (DLTs) of diarrhea and vomiting in absence of maximum supportive care. No DLTs were observed on DL-1 (n=6), therefore, DL1 was re-explored (n=6) with no DLTs, confirming this as RP2D. Most common treatment-related grade 3 or 4 adverse events were anemia (23.7%) and leukopenia (10.5%).Of 32 subjects evaluable for response, 6 (19%) had partial response (PR) with a PR rate of 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlation between response and immune activity, as well as alterations in cell cycle and DNA damage response genes. Therapy resistance was associated with receptor tyrosine kinase (RTK) and RAS-MAPK pathway activity, as well as metabolism and epigenetics.InterpretationThe combination of olaparib and capivasertib is well tolerated and demonstrates evidence of durable activity in women’s cancers, with particularly promising response in endometrial cancer. Importantly, tumor samples acquired pre and on-therapy can help predict patient benefit.FundingAstraZeneca, MDACC Moonshots Program, MDACC Support Grant CA016672 NCI SPOREs in Ovarian (CA217685) and Uterine (CA098258) Cancer and a kind gift from the Miriam and Sheldon Medical Research Foundation. AZD5363 was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

OBJECTIVE: To evaluate the utility of patient-reported outcomes (PROs) to measure physical functioning in perioperative care for patients with gynecological (GYN) tumors. METHODS: 180 patients with GYN tumors undergoing open surgery participated in this longitudinal study. The physical functioning was measured by a subjective PRO tool, the Interference subscales of the MD Anderson Symptom Inventory (MDASI-I); as well as by an objective tool, the Timed Up & Go test (TUGT), perioperatively. Longer time (>20 seconds) needed to complete the TUGT was defined as “Prolonged”. Patients completed EuroQoL-5D as well. The association between the scores of MDASI-I items and TUGT was assessed via the Spearman correlation coefficient. The known-group validity was assessed using the t-test and Cohen’s D effect size. RESULTS: Compliance rates at preoperative, discharge and postoperative time points of MDASI-I were 98%, 95%, 96%; while TUGT completion rates were 92%, 75%, and 80%, respectively. Patients who had refused TUGT at discharge reported a significantly worse “MDASI-general activity” score compared to patients who completed TUGT (mean score of 7.00 vs. 5.38, P=0.020). Patient-reported “Walking” on MDASI-I significantly differentiated patients with prolonged vs. those with frail/normal TUGT at discharge (mean score of 4.89 vs. 2.79, Cohen’s d effect size = 0.82, P < 0.001) MDASI-I demonstrated excellent known-group validity per performance status and for the EuroQoL-5D subscales. CONCLUSION: Patient-reported physical functioning impairment after GYN surgery correspond with observed worse scores of the objective functioning measure test (TUGT). MDASI-I assessment represents a feasible and valid tool to evaluate functional status and warrants further implementation in the perioperative setting.

183 Background: For advanced upper gastrointestinal (GI) cancers, patient-reported symptoms are driven by both disease and treatment toxicities. This real-world longitudinal study was designed to evaluate patient-reported outcomes (PROs) of symptom burden and functioning among patients (pts) treated with anti-cancer therapy. Methods: Adult pts with advanced esophageal, gastroesophageal junction (GEJ), or gastric cancer were invited to participate in a prospective, longitudinal study. PRO assessment included pre-treatment and weekly completion of the M.D. Anderson Symptom Inventory GI module (MDASI-GI) as pts initiated a new line of therapy. Clinical and disease characteristics and treatment details were obtained from electronic health records. Up to 12 weeks longitudinal PRO data were analyzed using mixed-effect modeling with random intercept. Pts were classified into high or low symptom groups by group-based trajectory modeling. Time to deterioration in functioning (defined as a ≥2-point increase from baseline on 0-10 scale) was examined with Kaplan-Meier method. Results: At the interim analysis, 76 pts had enrolled: 33 (43%) were chemotherapy naïve for advanced disease, 18 (24%) had received 1 line of therapy, 14 (18%) had received > 1 line of therapy, and 11 (14%) were excluded from this analysis due to study discontinuation without follow-up assessment. Among the 65 eligible pts in this analysis, 46 (70.8%) were male, most were white (n = 56, 86.2%), and 44 (67.7%) had an ECOG performance status score of 0-1. Pain, fatigue, disturbed sleep, lack of appetite and inability to eat were the most common severe symptoms reported prior to and during therapy. Pts who had received one line of therapy reported worsening symptoms of pain, fatigue, lack of appetite, difficulty swallowing, and reduced general activity, work, and enjoyment of life over time (group and time interaction P 1 line of prior therapy had increased neuropathy symptoms (numbness/tingling) than those who were treatment-naïve ( P= 0.022). The median time to functioning deterioration of ≥2 points from baseline on the MDASI-“General activity” was 7 weeks. Up to 57% of pts were classified into high symptom trajectory group of pain, fatigue, disturbed sleep, and drowsiness with moderate to severe symptoms (≥4 points out of possible 10) over time; group membership was related to moderate to severe symptoms at baseline, after adjusting for age, sex, ECOG performance status, cancer site and prior therapies. Conclusions: This real-world observational study suggests that pts with advanced stage upper GI cancer undergoing standard therapy report high symptom burden. These preliminary findings support the use of a targeted symptom monitoring using well-defined PROs during active therapy, thereby adding the knowledge obtained from PROs to improve routine patient care.

6079 Background: The chronic nature of treatment for ovarian cancer (OC) can place women at increased risk of financial toxicity (FT) from ongoing direct and indirect costs coupled with potential loss of income. We explored FT and its association with anxiety, depression, and quality of life over time in women with recurrent OC. Methods: Women with recurrent OC enrolled in a longitudinal study were given the following validated instruments at baseline and every 3 months: FACIT Comprehensive Score for Financial Toxicity (COST), GAD-7 (anxiety), CES-D (depression) and FACT-Ovary. Mixed models were performed on longitudinal data over 12 months of follow-up. Multivariable analysis of demographic data was performed. Results: 225 patients were divided into low FT (top 2 terciles, n = 152) and high FT (bottom tercile, n = 73,) by baseline COST scores. The median age was 59 (range 22.9-78.9). There were no significant differences between the groups in regards to marital status, number of people in household or education level. There were significant differences between the low and high financial toxicity groups in terms of median age (low FT = 61 yrs vs. high FT = 54 yrs, p < 0.0001); race (5.4% black in low FT vs. 15.1% in high FT, p = 0.04), number of children < 18 years in the home ((p = 0.02), employment status p( < 0.0001) and annual income p( < 0.0001). On multivariable analysis, only income and age remained significantly associated with FT. The mean baseline COST score in the low FT group was 34 vs. 16 in the high FT group. Interestingly, pts with low baseline FT had significant worsening of FT over the 12 month time period while those with high FT had slight improvement over time. Consistently, the high FT group had higher scores on screening measures for anxiety and depression, as well as lower overall quality of life which persisted over time. Conclusions: Financial toxicity is a measurable and clinically relevant patient reported outcome. The cohort of women with high FT demonstrated higher mean scores on screening measures for depression and anxiety as well as persistently lower quality of life. Targeted interventions to decrease financial toxicity may provide more global improvements in mental health and quality of life.

e18083 Background: The symptom burden and functional recovery of patients after hospital discharge is important to understand in order to provide more patient centered care. This study evaluated longitudinal quantitative patient-reported outcome (PRO) data using a validated PRO symptom and functional interference measure after hospital discharge from open gynecologic surgery. Methods: Patients with GYN tumors scheduled for laparotomy at MD Anderson Cancer Center were recruited prospectively. The MD Anderson Symptom Inventory gynecology perioperative care module (MDASI-PeriOp-GYN) was used to assess symptoms post discharge on Day 3, 7, and weekly up to 6 weeks. Median survival time and log-rank test was used for comparing time to return to no or mild level (≤3 in a 0-10 scale) of symptoms during the post discharge period between groups who discharged within and beyond the median length of stay (LOS) days. Results: From Feb 2018–Dec 2018, 83 patients were evaluable. The median LOS was 3 days. Compared to patients who were discharged within 3 days (70% of sample), 30% patients were discharged after 3 days after surgery (range of 4-10 days). Except distress, all other PROs on MDASI-PeriOp-GYN were not significantly different between the two groups on the day of discharge. However, those late discharged patients had significantly delayed recovery on fatigue (median recovery time > 56 days vs. 17 days), dry mouth (10 days vs. 6 days) (both P< .01), and drowsiness (12 days vs. 6 days, P< .05). The recovery of physical functioning (MDASI general activity interference item) was prolonged among late discharged patients compared to patients who were discharge within 3 days ( > 56 days vs. 30 days, P< .01). Conclusions: Even though all patients were under a standardized Enhanced Recovery Program, about 30% of patients post GYN open surgery were discharged beyond the median LOS. Patients in this group continued to have delayed recovery after hospital discharge as evidenced by persistent fatigue and slower return of physical functioning. Implementation of post-discharge PROs may help identify patients at risk for prolonged recovery and help triage patients to more intensive supportive care.

e18078 Background: Using patient-reported outcomes (PRO) in perioperative care is increasingly common in patients undergoing major surgery. Few reports relate the patient’s symptomatic status using validated PROs during hospitalization with other outcomes, such as length of stay (LOS). Methods: Patients with GYN tumors scheduled for open surgery at MD Anderson Cancer Center were recruited prospectively. The MD Anderson Symptom Inventory gynecology perioperative care module (MDASI-PeriOp-GYN) was used to assess symptoms daily during hospitalization. Longitudinal analysis compared patient’s PROs between groups who were discharged within and beyond the median LOS. Results: From Feb 2018–Dec 2018, 83 patients were evaluable. The median LOS was 3 days. 70% of patients were discharged within 3 days, and 30% were hospitalized longer (defined as late discharge group, range 4-10 days). The median LOS for the two groups was 5.64 vs. 2.41 days, P < .0001. Compared to patients who were discharged within 3 days, late discharge patients had longer surgical time (310 min vs. 209 min, P < .0001), and greater operative blood loss (668mL vs. 289 mL, P < .001). Additionally, more patients in the late discharge group had a worse performance status (ECOG PS 2-3: 24% vs. 3.5%, P < .05), and higher comorbidity (Charlson comorbidity Index > 1: 92% vs. 69%, P < .05), and more used opioids within 6 month pre-surgery (16% vs. 1.7%, P < .05). For all patients, the 5 worst symptoms during the first 3 hospital days were pain, fatigue, drowsiness, dry mouth, bloating. Late discharge patients reported significant more severe pain, distress, dry mouth, and interference with walking during the first 3 days post-surgery (all P < .05). Conclusions: Despite all patients undergoing standardized perioperative care on an Enhanced Recovery pathway, this study demonstrates how baseline and intraoperative factors are associated with longer LOS and more severe symptom burden, especially pain and interference with walking.