Background: Meibomian gland disfunction is a common finding in glaucoma patients under topical treatment. Objective:To evaluate and analyze the Meibomian morphology in patients with different Glaucoma Topical Treatments.Methods: Cross-sectional retrospective study.88 patients: 15 control and 73 glaucoma patients classified: a) Latanoprost-Timololcarbonic anhydrase inhibitor b) Latanoprost-Timolol, c) Timolol, d) Latanoprost, and e) Travoprost-Timolol (Polyquad).Slit-lamp examination and OSDI® questionnaire was evaluated.Glandular number, length, thickness, tortuosity percentage and tarsal/ glandular area (Meiboscore) was obtained from each Meibography.Results: Control presented the highest gland number (21.2 ± 5.3 upper and 17,3 ± 5,68 lower eyelid), longest glands (6,0 ± 0,94 mm upper and 3,2 ± 0,85 mm lower eyelid), thinnest glands (0,6 ± 0,14 mm upper and 0,8 ± 0,15 lower eyelid) and lower upper eyelid Meiboscore (63,3 ± 12,68%).Latanoprost-Timolol and carbonic anhydrase inhibitor presented the lowest tortuosity (27,1 ± 18,34% upper and 12,9 ± 13,99% lower eyelid).Latanoprost group presented the thickest glands (0,75 ± 0,10 mm upper and 0,94 ± 0,2 mm lower eyelid).The lowest Meiboscore in lower eyelid was Travoprost-Timolol (Polyquad) (59,7 ± 14,26%).Conclusions: Glaucoma Meibomian glands groups showed alterations compared to control.Polyquad showed less alterations in Meiboscore value than BAK groups, but not in all the parameters.Correlation with treatment but without cumulative preservative dose indicate another compounds effect.Upper eyelid glands seem to be affected earlier in these patients.Meibomian gland study should be considered as part of treatment decision and following in glaucoma patients.
131 Background: The phase 3, randomized KEYLYNK-010 trial (NCT03834519) of pembro + ola vs next-generation hormonal agent (NHA) abi or enza did not significantly improve rPFS or OS in molecularly unselected pts with mCRPC treated with prior NHA and docetaxel. The study was stopped for futility after the second prespecified interim analysis. PROs for pembro + ola vs NHA in KEYLYNK-010 are presented. Methods: Pts were randomly assigned 2:1 to receive pembro 200 mg IV Q3W for ≤35 cycles (~2 y) + ola 300 mg orally BID or NHA (either abi 1000 mg orally QD + prednisone 5 mg orally BID, if pt previously received enza, or enza 160 mg orally QD if pt previously received abi). PROs were evaluated in pts who received ≥1 dose of study treatment and had ≥1 PRO assessment. FACT-P and BPI-SF were administered at baseline, Q3W until wk 24, Q6W until wk 72, and Q12W thereafter for ≤2 y. Time to pain progression (TTPP) based on BPI-SF was a prespecified secondary end point. Prespecified exploratory end points included least squares mean (LSM) change from baseline to wk 15 for FACT-P total and subscales scores (FACT-G total, TOI, FAPSI-6, FWB, PWB, and PCS) and BPI-SF scores (pain interference, pain severity, and worst pain), and time to deterioration (TTD) and overall improvement rate in FACT-P total and subscale scores. Differences were evaluated using 2-sided nominal P values not controlled for multiplicity. Results: A total of 793 pts were randomly assigned to pembro + ola (n = 529) or NHA (n = 264). As of January 18, 2022, median follow-up was 18.7 mo (range, 6.1-31.7). In all randomized pts, completion rate for FACT-P and BPI-SF at baseline and wk 15 was >84% and >57%, respectively. No differences were observed in the median TTPP for pembro + ola (13.5 mo [95% CI, 9.7-NR]) vs NHA (12.0 mo [95% CI, 10.1-NR]; HR, 0.95 [0.72-1.26]). No LSM differences were observed in FACT-P total scores (pembro + ola, –4.62 [95% CI, –6.47 to –2.77] vs NHA, –5.86 [95% CI, –8.58 to –3.13]) or BPI-SF scores (Table). There were no differences in TTD in FACT-P total, FACT-G total, TOI, FAPSI-6, FWB, PWB, and PCS scores between groups. A numerically higher proportion of pts had improved + stable FACT-P total scores for pembro + ola (44.0%) vs NHA (39.0%). FACT-P and BPI-SF scores were generally maintained across all evaluated time points up to wk 81. Conclusions: No clinically meaningful changes from baseline were observed in HRQoL or disease-related symptom scores with either pembro + ola or NHA. PRO scores were generally similar between pembro + ola and NHA at all analyzed time points, suggesting HRQoL was maintained in heavily pretreated pts receiving pembro + ola. Clinical trial information: NCT03834519 . [Table: see text]
Objectives. This study aimed to evaluate visual display terminal (VDT)-related digital eye strain (ES) and dry eye disease (DED) symptoms in subjects whose work was changed to teleworking (TW) during the coronavirus pandemic. Methods. A digital self-reported survey was conducted on subjects in TW, including demographics, medical history, VDT time and ES-related symptoms before and during the pandemic and DED (dry eye questionnaire 5 [DEQ-5] questionnaire). Results. A total of 1797 questionnaires were analyzed. Mean age was 40.5 (SD 11.1) years, and 69.9% were female. The mean number of TW weeks was 10.2 (SD 3.0). The total VDT total hours increased from 7.4 (SD 3.3) to 9.5 (SD 3.3) (p < 0.001). All ES symptoms presented a significant increase (p < 0.001). The mean DEQ-5 score was 8.3 (SD 4.9). The oldest group presented lower values, and women had a higher score (p < 0.001). Additionally, 28.6% of the subjects were classified with severe DED, and the variables associated with a logistic regression model were total VDT hours, female gender, refractive surgery, rosacea, depression, previous DED, keratoconus and blepharitis. Conclusions. The number of VDT hours seemed to be a relevant factor for increase in ES symptoms and a high prevalence of DED during the pandemic period.
4002 Background: CheckMate 649 is the largest randomized, global phase 3 study of 1L programmed death (PD)-1 inhibitor–based therapy in GC/GEJC/EAC. 1L NIVO + chemo demonstrated superior overall survival (OS) vs chemo, with progression-free survival (PFS) benefit and an acceptable safety profile in pts whose tumors expressed PD-ligand (L)1 at combined positive score (CPS) ≥ 5 and ≥ 1, and in all randomized pts (Moehler et al. Ann Oncol 2020). We report additional data for all randomized pts. Methods: Eligible pts had previously untreated, unresectable advanced or metastatic GC/GEJC/EAC. Known HER2-positive pts were excluded. Pts were randomized to receive NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded central review in PD-L1 CPS ≥ 5 pts. Hierarchically tested secondary endpoints were OS in PD-L1 CPS ≥ 1 and all randomized pts. Results: At 12-month minimum follow-up for 1581 randomized pts, NIVO + chemo had a statistically significant OS benefit vs chemo (HR 0.80 [99.3% CI 0.68–0.94; P = 0.0002]) in all randomized pts; PFS benefit was also seen (HR 0.77 [95% CI 0.68–0.87]). OS benefit was observed in multiple prespecified subgroups, consistent with the primary population. Grade 3–4 treatment-related adverse events (TRAEs) were reported in 59% (NIVO + chemo) and 44% (chemo) of pts. TRAEs with potential immunologic etiology (select TRAEs; sTRAEs) are shown in the table. Pts in the NIVO + chemo arm had decreased risk of symptom deterioration on treatment vs those in the chemo arm (HR 0.77 [95% CI 0.63–0.95; P = 0.0129]). Tolerability as measured by the FACT-Ga GP5 item was similar in both treatment groups. Conclusions: The addition of NIVO to chemo demonstrated improved OS and PFS benefit in all randomized pts, along with an acceptable safety profile and maintained tolerability as well as QoL, providing further support for NIVO + chemo as a standard 1L treatment for advanced GC/GEJC/EAC. Clinical trial information: NCT02872116. [Table: see text]
Abstract Background: First-line nivolumab (NIVO) + chemotherapy (chemo) showed superior overall survival (OS) vs chemo, but NIVO + ipilimumab (IPI) vs chemo did not meet the prespecified OS boundary for significance in patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC) in CheckMate 649. However, NIVO + IPI resulted in more durable responses and higher 24-month OS rates vs chemo. We present exploratory biomarker analyses of NIVO + IPI vs chemo. Methods: Tumor mutational burden (TMB) was derived from whole exome sequencing of baseline tumor tissue and matching blood. TMB-high (TMB-H) was defined as ≥ 199 mutations/exome. Gene expression signatures (GES), including 12-gene chemokine, 2-gene regulatory T cell (Treg), 15-gene fibroblast, and 5-gene endothelial, were assessed via RNA sequencing of baseline tumor tissue. GES subgroups were defined by signature score tertiles. Results: 813 patients were randomized to receive NIVO + IPI or chemo; 366 were evaluable for TMB (NIVO + IPI 45%, chemo 45%), and 402 were evaluable for GES (NIVO + IPI 49%, chemo 50%). OS HR for NIVO + IPI vs chemo was numerically lower in the TMB-H (6% of evaluable patients, HR 0.31) vs TMB-low (94% of evaluable patients, HR 0.87) subgroup (Table). Multiple GES subgroups showed OS benefit with NIVO + IPI vs chemo, including chemokine-high, Treg-high, fibroblast-low, and endothelial-low subgroups (Table). Additional analysis on microsatellite instability and GES in programmed death ligand-1 combined positive score subgroups will be presented. Conclusions: This exploratory analysis suggests that there are patient subgroups with GC/GEJC/EAC that may benefit from dual immune checkpoint blockade. Clinical utility of these biomarkers should be prospectively validated in future trials. Overall survival All randomized patients HR (95% CI) 0.89 (0.77-1.03) All evaluable HR (95% CI) High, n (%) HR (95% CI) Medium, n (%) HR (95% CI) Low, n (%) HR (95% CI) TMB (n = 366) 0.81 (0.65-1.00) 21 (6) 0.31 (0.10-0.95) - 345 (94) 0.87 (0.70-1.09) GES (n = 402) Chemokine 0.82 (0.67-1.01) 134 (33) 0.59 (0.40-0.86) 134 (33) 0.92 (0.65-1.32) 134 (33) 0.98 (0.68-1.40) Treg 134 (33) 0.59 (0.41-0.86) 134 (33) 0.91 (0.64-1.30) 134 (33) 1.07 (0.75-1.52) Fibroblast 134 (33) 0.98 (0.69-1.40) 134 (33) 0.94 (0.66-1.35) 134 (33) 0.63 (0.43-0.91) Endothelial 134 (33) 0.97 (0.68-1.38) 134 (33) 0.94 (0.65-1.34) 134 (33) 0.65 (0.45-0.94) OS HR data are unstratified for NIVO + IPI vs chemo. Citation Format: Yelena Y. Janjigian, Kohei Shitara, Jaffer Ajani, Markus Moehler, Jin Yao, Lin Shen, Marcelo Garrido, Carlos Gallardo, Lucjan Wyrwicz, Kensei Yamaguchi, Tomasz Skoczylas, Arinilda Bragagnoli, Tianshu Liu, Michael Schenker, Patricio Yañez, Ruben Kowalyszyn, Michalis Karamouzis, Thomas Zander, Kynan Feeney, Elena Elimova, Raheel Nathani, Ruslan Novosiadly, Ming Lei. Nivolumab plus ipilimumab vs chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma: CheckMate 649 biomarker analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT037.
Pembrolizumab is approved for recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation. cSCC is an immunogenic cancer characterized by high tumor mutational burden with ultraviolet signature, and tumor antigen overexpression. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens specifically tailored for each patient, derived from their tumor-specific mutational profile. V940 plus pembrolizumab significantly improved recurrence-free survival over pembrolizumab alone for completely resected, high-risk, stage IIIB/C/D and IV cutaneous melanoma. INTerpath-007 is an open-label, randomized, adaptive phase 2/3 trial (NCT06295809) evaluating efficacy and safety of neoadjuvant plus adjuvant treatment with pembrolizumab plus V940 versusstandard of care (surgery (SOC) for resectable locally advanced cSCC.
Methods
Patients with histologically confirmed resectable stage II-IV (M0) cSCC, no prior systemic therapy, and adequate tumor sample suitable for next-generation sequencing will be enrolled. In phase 2,600 patients will be randomly assigned 5:5:2 to Arm A (pembrolizumab plus V940 plus surgery), Arm B (surgery), and Arm C (pembrolizumab plus surgery). Patients in Arm A will receive pembrolizumab 400 mg intravenously Q6W (2 neoadjuvant plus 9 adjuvant doses) plus V940 1 mg intramuscularly Q3W (2 neoadjuvant plus 7 adjuvant doses). Patients in Arm C will receive pembrolizumab 400 mg IV Q6W. Patients in Arm B will proceed straight to surgery. Radiation will be allowed per investigator's discretion after surgery in all arms. If the trial expands to phase 3, 412 additional patients will be randomly assigned 1:1 to Arms A and B, for a total of 1,012 patients. Imaging will be performed at screening (all arms), 6 weeks (Arms A and C), 3–6 weeks post-surgery (all arms) ± day 1 of the adjuvant period (Arms A and C), every 12 weeks for years 1–3, and then every 6 months thereafter (all arms). The primary objective is to compare event-free survival (EFS) by investigator assessment in patients treated with pembrolizumab plus V940 compared with SOC. Key secondary objectives are to compare pathological complete response (pCR) by blinded independent central review and overall survival (OS) in patients treated with pembrolizumab plus V940 compared with SOC. Descriptive evaluation of EFS, pCR, and OS for pembrolizumab plus V940 versus pembrolizumab alone will be an exploratory objective. Recruitment is underway in Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, France, Germany, Hungary, Israel, Italy, New Zealand, Norway, Poland, Romania, Spain, Turkey, United Kingdom, and United States.
Trial Registration
ClinicalTrials.gov, NCT06295809.
Ethics Approval
The protocol was approved by the appropriate ethics committee or institutional review board at each center, and the trial was conducted per Good Clinical Practice guidelines and in accordance with the principles of the Declaration of Helsinki. All patients provided written informed consent.
To evaluate dry eye (DE) and subjective visual display terminal (VDT)-related symptoms in university students who moved their classes online due to the COVID-19 pandemic.Cross-sectional study of students who were taking online classes. In May 2020, the participants completed a Dry Eye Questionnaire (DEQ-5) and a self-report survey, which included demographics, medical history, information on the use of VDT and presence of VDT-related symptoms. Participants were classified as having mild/moderate (7-12) or severe (>12) DE symptoms based on their DEQ-5 score. The associations between severe DE symptoms and relevant factors were also evaluated.The data of 1450 eligible students were analyzed. The mean age of the participants was 21.1 (2.7) years. 42.8% of the participants had mild/moderate DE symptoms, whereas 34.7% had severe symptoms. Associated factors for severe DE were female sex (OR = 2.57, CI [1.97-3.35]), allergic disease (OR = 1.63, CI [1.24-2.13]), previous dry eye diagnosis (OR = 13.49, CI [7.10-25.63]), keratoconus (OR = 5.56, CI [1.27-24.44], contact lens use (OR = 1.77, CI [1.24-2.53]) and duration of VDT use (OR = 1.02, CI [1.01-1.05]). Prior to the pandemic, the mean reported duration of VDT use was 9.8 (4.7) hours; this increased to 15.9 (5.8) hours during the online classes (p < .001). 80.6% of the participants reported a global increase in VDT-related symptoms.Students taking online classes had a high frequency of DE symptoms. They also reported a significant increase in VDT-related symptoms. DE should be considered as an emerging health problem among the young population, which is probably related to the recent changes in lifestyle.
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