Perceived Public Stress Among Jordanians During the COVID-19 Outbreak

ABSTRACT Objectives: Outbreaks and containment measures implemented to control them can increase stress in affected populations. The impact of the coronavirus disease 2019 (COVID-19) outbreak on perceived stress levels in the Jordanian population is unknown. The aim of the study was to determine the perceived stress level and factors associated with it in the Jordanian population during the COVID-19 outbreak. Methods: Required data, such as those from the Perceived Stress Scale (PSS-10) and possible predictors of perceived stress, were collected through a Web-based survey. Statistical analysis was conducted through SPSS. Results: The mean (SD) of perceived stress score was 19.8 (6.7). Regression analysis revealed that stress was increased in females, young adults, usually being stressed more than others by a health problem, increased perceived severity of the disease, increased overall worry score, and student’s worry regarding their studies/graduation. Perceived stress was decreased if participants’ self-rated health status score increased. Conclusions: In the context of increasing public health preparedness, the results of this study can be used in designing interventions to alleviate stress in susceptible segments of the Jordanian community.

TPExtreme randomized trial: Quality of Life (QoL) and survival according to second-line treatments in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).

6507 Background: TPExtreme trial comparing EXTREME regimen to the taxane-based TPEx confirmed the encouraging survival results of the TPEx regimen, despite lack of significant overall survival (OS) increase, with a significantly lower toxicity than the EXTREME regimen. Herein, the QoL and exploratory analyses of survival according to 2nd line treatments focusing on immunotherapy (IO) are presented. Methods: Randomized (1:1), open-label trial. Main inclusion criteria were R/M HNSCC not suitable for loco-regional treatment, age 18-70 years, PS < 2, creatinin clearance > 60ml/min, prior cisplatin < 300 mg/m². 539 pts were enrolled over a period of 37 months (mo). QoL was evaluated with QLQ-C30 questionnaire at baseline, week(W)12, W18, W26 and analyzed by linear mixed model. The primary QoL endpoint was the Global Health Status score. 2nd line treatments were collected for 501 (93%) patients (pts), 256 in the EXTREME arm and 245 in the TPEx arm. Results: The percentage of QLQ-C30 questionnaires filled at baseline, W12, W18 and W26 were similar in the 2 arms, 89%, 52%, 43%, and 39% in the EXTREME arm and 91%, 59%, 40%, and 37% in the TPEx arm, respectively.. Higher scores of Global Health Status (p = 0.02), physical functioning (p = 0.009) and role functioning (p = 0.013) and lower scores of appetite loss (p = 0.041) were observed in the TPEx arm than in the EXTREME arm. No significant difference was observed for the other scores. In 2nd line treatment, 120 (47%) pts in the EXTREME arm and 109 (44%) in the TPEx arm received chemotherapy +/- cetuximab (CT); 41 (16%) pts in the EXTREME arm and 41 (17%) in the TPEx arm received IO, mainly anti-PD-1/PD-L1. 79% and 85% of these 2nd line treatments were given after progression in EXTREME and TPEx arms respectively. Median OS (95%CI) since randomization was 17.6 (15.2 – 19.5) mo with CT and 19.4 (13.4 – 22.3) mo with IO in the EXTREME arm vs 14.9 (13.0 – 16.3) and 21.9 (15.9 – 35.0) mo in the TPEx arm (interaction test p = 0.077) respectively. Median OS since start of 2nd line was 9.3 mo with CT and 8.3 mo with IO in the EXTREME arm, and 7.1 and 11.6 mo respectively in the TPEx arm. Conclusions: An improvement in the QoL of patients was observed in the TPEx arm compared to that of the EXTREME arm. Exploratory analysis showed that the taxane-based TPEx regimen followed by IO in 2nd line could provide interesting median OS for pts who need CT in 1st line, with less toxicity than EXTREME. This sequential treatment deserves to be compared to a strategy that starts with Platinum+5FU+pembrolizumab. Clinical trial information: NCT02268695 .

Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.

Safety Profile of Trabectedin in Combination With Liposomal Pegylated Doxorrubicin in Relapsed Ovarian Carcinoma: Considerations for Optimal Management

The toxicity profile of trabectedin in the OVA-301 trial, that combined trabectedin with pegylated liposomal doxorubicin for the treatment of patients with ovarian cancer, has shown to be predictable and manageable. No unexpected toxicities were found, with neutropenia and transient increase in transaminases as the most common adverse events reported. The elevation in transaminases appeared early and generally decreased in incidence and intensity over subsequent cycles, with no major clinical consequences. A similar safety profile was seen in the analysis of the older patients in the trial. There were no detrimental effects in quality of life with the combination. Moreover, the Global Health Status score was better for the combination arm in those patients with a PFI of 6 to 12 months that were in response after 5 cycles. Trabectedin with pegylated liposomal doxorubicin is not associated with cumulative end-organ toxicities (renal, cardiac, or neurological toxicities). The toxicity profile is different from other second-line strategies without the presence of inconvenient side effects, such as alopecia, hypersensitivity reactions, hand-foot syndrome, or mucositis.

Patient-Reported Quality of Life In Elderly, Newly Diagnosed Multiple Myeloma Patients Treated with Bortezomib-Based Regimens: Results From the Phase 3b UPFRONT Study

Abstract 3026 Background: UPFRONT is an ongoing US community-based phase 3b study designed to compare the safety and efficacy of three bortezomib (Velcade®, Vc)-based regimens, Vc-dexamethasone (VcD), Vc-thalidomide-dexamethasone (VcTD), and Vc-melphalan-prednisone (VcMP), followed by Vc maintenance therapy, in previously untreated multiple myeloma (MM) patients who were ineligible for high-dose therapy and autologous stem cell transplantation (HDT-SCT). Efficacy data have been presented elsewhere; here we present patient-reported quality of life (QoL) data after 300 patients had the opportunity to undergo the entire 13-cycle treatment period (8 Vc-based induction cycles and 5 Vc maintenance cycles). Methods: Patients with symptomatic, measurable MM were randomized (1:1:1) to receive 49 weeks of therapy: 24 weeks (eight 21-day cycles) of induction with VcD, VcTD, or VcMP (VcD: Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcTD: Vc 1.3 mg/m2, days 1, 4, 8, 11; T 100 mg/d, d1–21; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcMP: Vc 1.3 mg/m2, days 1, 4, 8, 11; M 9 mg/m2, and P 60 mg/m2, day 1–4, every other cycle), followed by 25 weeks (five 35-day cycles) of maintenance with Vc alone (1.6 mg/m2, days 1, 8, 15, 22). Patient-reported QoL was recorded using the EORTC QLQ-C30 questionnaire, which assesses global health status, physical, role, cognitive, emotional, and social functions, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Patients completed the questionnaire prior to dosing on cycle 1, day 1 (baseline), prior to dosing on day 1 of every odd cycle, at the end of treatment visit, and every 12 weeks thereafter. Here we present updated study results after 300 patients had the opportunity to undergo the entire 13-cycle treatment period, focusing on change in global health status score over time; no adjustment was made for missing cases or patient deaths. Results: Patient baseline characteristics were well balanced across the three treatment arms. Patients in the VcD, VcTD, and VcMP arms had median ages of 73.5, 73.0, and 72.0 years, respectively; 85%, 64%, and 74% had ISS stage II/III; 22%, 27%, and 28% were non-Caucasian; and 51%/25%/24%, 55%/30%/14%, and 62%/24%/15% had Charlson comorbidity index 0/1/≥2 in the VcD, VcTD, and VcMP arms, respectively. Patients received a median of 9 (VcD), 6 (VcTD), and 7 (VcMP) treatment cycles (induction + maintenance); 56%, 33%, and 43% of patients, respectively, received Vc maintenance. In the VcD, VcTD, and VcMP arms, Vc dose intensity (mean ratio of doses received/doses planned) was 76%, 63%, and 69% during induction, and 73%, 77%, and 85% during maintenance, respectively. After 13 treatment cycles, the rates of grade ≥3 adverse events (AEs) were 74%, 86%, and 80% in the VcD, VcTD, and VcMP arms. The incidence of serious AEs was highest in the VcTD arm (61%, vs 57% and 51% with VcD and VcMP), as was the rate of study drug discontinuation due to AEs (41%, vs 29% and 35% with VcD and VcMP). Global health status score by cycle is shown in the Figure, with number of patients with available QoL data in each arm indicated below. In all three arms, for those patients with available QoL data, global health status score at the end of cycle 12 was greater than at baseline and at the end of cycle 8 (end of Vc-based induction therapy). In the induction phase, global health status score remained stable in the VcD arm and transiently decreased in the VcMP arm at cycle 4, before increasing to above baseline levels. A similar trend was seen for the VcTD arm; global health status score started decreasing at cycle 2 but took slightly longer to increase, possibly due to the increased incidence of AEs in the VcTD arm. Similar trends were seen for other EORTC QLQ-C30 function and symptom scores. Conclusions: Although there was some variability during the study, by the end of the treatment period patients who received one of the three Vc-based regimens reported improvements in QoL compared with baseline values. The study is ongoing and patients continue to be followed for assessment of patient-reported QoL and long-term outcomes. Updated QoL data, including the correlation between change in QoL and best response achieved, will be presented. Disclosures: Niesvizky: Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Off Label Use: Discussion of Velcade in a novel combination in frontline myeloma is included. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Cephalon: Speakers Bureau; Dendreon: Speakers Bureau. Gabrail:Millennium Pharmaceuticals, Inc.: Research Funding. Charu:Amgen: Equity Ownership, Research Funding; Pfizer: Equity Ownership; GSK: Equity Ownership, Research Funding; Lilly: Equity Ownership, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Equity Ownership. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment. Reeves:Celgene: Equity Ownership.