Browsing by Author "Jalal, Shadia I."
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Item 24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer(Elsevier, 2018) Borghaei, Hossein; Langer, Corey J.; Gadgeel, Shirish; Papadimitrakopoulou, Vassiliki A.; Patnaik, Amita; Powell, Steven F.; Gentzler, Ryan D.; Martins, Renato G.; Stevenson, James P.; Jalal, Shadia I.; Panwalkar, Amit; Yang, James Chih-Hsin; Gubens, Matthew; Sequist, Lecia V.; Awad, Mark M.; Fiore, Joseph; Saraf, Sanatan; Keller, Steven; Gandhi, Leena; Medicine, School of MedicineIntroduction Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. Methods A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). Results As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. Conclusions The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.Item A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study(Frontiers Media, 2021-09-17) Mamdani, Hirva; Schneider, Bryan; Perkins, Susan M.; Burney, Heather N.; Kasi, Pashtoon Murtaza; Abushahin, Laith I.; Birdas, Thomas; Kesler, Kenneth; Watkins, Tracy M.; Badve, Sunil S.; Radovich, Milan; Jalal, Shadia I.; Surgery, School of MedicineBackground: Most patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients. Methods: We conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population. Results: Thirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56-84%) with median RFS of 21 months (95% CI, 14-40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05-0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15-0.93, p = 0.0351, respectively). Conclusions: Adjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.Item Acceptance and Commitment Therapy for Symptom Interference in Advanced Lung Cancer and Caregiver Distress: A Pilot Randomized Trial(Elsevier, 2019) Mosher, Catherine E.; Secinti, Ekin; Hirsh, Adam T.; Hanna, Nasser; Einhorn, Lawrence H.; Jalal, Shadia I.; Durm, Gregory; Champion, Victoria L.; Johns, Shelley A.; Psychology, School of ScienceContext Advanced lung cancer patients typically have a poor prognosis and many symptoms that interfere with functioning, contributing to high rates of emotional distress in both patients and family caregivers. There remains a need for evidence-based interventions to improve functional outcomes and distress in this population. Objectives This pilot trial examined the feasibility and preliminary efficacy of telephone-based Acceptance and Commitment Therapy (ACT) for symptomatic, advanced lung cancer patients and their distressed family caregivers. Primary outcomes were patient symptom interference with functioning and patient and caregiver distress. Methods Symptomatic, advanced lung cancer patients and distressed caregivers (n = 50 dyads) were randomly assigned to six sessions of ACT or an education/support condition. Patients completed measures of symptom interference and measures assessing the severity of fatigue, pain, sleep disturbance, and breathlessness. Patients and caregivers completed measures of distress and illness acceptance and struggle. Results The eligibility screening rate (51%) and retention rate (76% at six weeks postintervention) demonstrated feasibility. No group differences were found with respect to patient and caregiver outcomes. Both groups showed a small, significant decrease in struggle with the illness over the study period, but did not show meaningful change in other outcomes. Conclusion Findings suggest that telephone-based ACT is feasible for many advanced lung cancer patients and caregivers, but may not substantially reduce symptom interference and distress. Low baseline levels of certain symptoms may have contributed to null findings. Next steps include applying ACT to specific, clinically meaningful symptom interference and varying intervention dose and modality.Item Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma(Elsevier, 2021) Mamdani, Hirva; Schneider, Bryan; Perkins, Susan M.; Burney, Heather; Kasi, Pashtoon Murtaza; Abushahin, Laith; Birdas, Thomas; Kesler, Kenneth; Watkins, Tracy M.; Badve, Sunil; Jalal, Shadia I.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Concurrent chemoradiation (CRT) followed by esophagectomy is a standard of care for resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma. The relapse rate is high among patients who do not achieve a pathologic complete response (pCR) following neoadjuvant CRT. Methods: We conducted a phase II study of durvalumab in patients with locally advanced esophageal and GEJ adenocarcinoma who have undergone preoperative CRT followed by R0 resection with histologic evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every four weeks for up to one year. The primary endpoint was 1-year relapse free survival (RFS). Findings: Thirty-seven patients were enrolled. The majority (64∙9%) had pathologically positive lymph nodes. One-year RFS was 73%, and median RFS was 21 months (95% CI, 14-40.4 months). Nineteen (51∙4%) patients had PD-L1 CPS of ≥1% and 7 (18∙9%) had PD-L1 CPS of ≥10%. There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10% (100% vs 66.7%, p=0.1551) and ≥1% (84.2% vs 61.1%, p=0.1510) cutoffs. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events, including pneumonitis(1), colitis(1), and hepatitis(1). Interpretation: Adjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ adenocarcinoma led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting.Item Adjuvant Epidermal Growth Factor Receptor Inhibitors in Non-Small Cell Lung Cancer(Alphamed Press, 2015-09) Lourdes, Laura S.; Jalal, Shadia I.; Hanna, Nasser; Department of Medicine, IU School of MedicineItem Barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients(Wiley, 2014-07) Mosher, Catherine E.; Winger, Joseph G.; Hanna, Nasser; Jalal, Shadia I.; Fakiris, Achilles J.; Einhorn, Lawrence H.; Birdas, Thomas J.; Kesler, Kenneth A.; Champion, Victoria L.; Psychology, School of ScienceOBJECTIVE: This study examined barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients (N=165) at two medical centers in the Midwestern United States. METHODS: Lung cancer patients completed an assessment of anxiety and depressive symptoms, mental health service use, barriers to using these services, and preferences for addressing emotional concerns. RESULTS: Only 45% of distressed patients received mental health care since their lung cancer diagnosis. The most prevalent patient-reported barriers to mental health service use among non-users of these services (n=110) included the desire to independently manage emotional concerns (58%) and inadequate knowledge of services (19%). In addition, 57% of distressed patients who did not access mental health services did not perceive the need for help. Seventy-five percent of respondents (123/164) preferred to talk to a primary care physician if they were to have an emotional concern. Preferences for counseling, psychiatric medication, peer support, spiritual care, or independently managing emotional concerns also were endorsed by many patients (range=40-50%). Older age was associated with a lower likelihood of preferring to see a counselor. CONCLUSIONS: Findings suggest that many distressed lung cancer patients underuse mental health services and do not perceive the need for such services. Efforts to increase appropriate use of services should address patients' desire for autonomy and lack of awareness of services.Item Blood-based tumor biomarkers in lung cancer for detection and treatment(2017-11) Mamdani, Hirva; Ahmed, Shahid; Armstrong, Samantha; Mok, Tony; Jalal, Shadia I.; Medicine, School of MedicineThe therapeutic landscape of lung cancer has expanded significantly over the past decade. Advancements in molecularly targeted therapies, strategies to discover and treat resistance mutations, and development of personalized cancer treatments in the context of tumor heterogeneity and dynamic tumor biology have made it imperative to obtain tumor samples on several different occasions through the course of patient treatment. While this approach is critical to the delivery of optimal cancer treatment, it is fraught with a number of barriers including the need for invasive procedures with associated complications, access to limited amount of tissue, logistical delays in obtaining the biopsy, high healthcare cost, and in many cases inability to obtain tissue because of technically difficult location of the tumor. Given multiple limitations of obtaining tissue samples, the use of blood-based biomarkers (“liquid biopsies”) may enable earlier diagnosis of cancer, lower costs by avoiding complex invasive procedures, tailoring molecular targeted treatments, improving patient convenience, and ultimately supplement clinical oncologic decision-making. In this paper, we review various blood-based biomarkers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), tumor derived exosomes, tumor educated platelets (TEPs), and microRNA; and highlight current evidence for their use in detection and treatment of lung cancer.Item Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE)(ASCO, 2017-08) Jalal, Shadia I.; Lavin, Philip; Lo, Gregory; Lebel, Francois; Einhorn, Lawrence; Medicine, School of MedicinePurpose To evaluate the efficacy of the addition of palifosfamide to carboplatin and etoposide in extensive stage (ES) small-cell lung cancer (SCLC). Patients and Methods MATISSE was a randomized, open-label, adaptive phase III study. Previously untreated patients with ES SCLC were randomly assigned in a 1:1 fashion to receive carboplatin at area under the serum concentration-time curve 5 on day 1 plus etoposide 100 mg/m2 per day on days 1 to 3 every 21 days (CE) or carboplatin at area under the serum concentration-time curve 4 on day 1 plus etoposide 100 mg/m2 per day plus palifosfamide 130 mg/m2 per day on days 1 to 3 every 21 days (PaCE). The primary end point was overall survival. Results In all, 188 patients were enrolled; 94 patients received CE and 94 patients received PaCE. The median age on both arms was 61 years. Six cycles of chemotherapy were completed on both arms of the study by approximately 50% of the patients. Serious adverse events were documented and did not differ significantly between patients receiving PaCE and those receiving CE. Median overall survival was similar between both arms with 10.03 months on PaCE and 10.37 months on CE (P = .096). Conclusion The addition of palifosfamide to CE failed to improve survival in ES SCLC.Item Coping Skills Practice and Symptom Change: A Secondary Analysis of a Pilot Telephone Symptom Management Intervention for Lung Cancer Patients and their Family Caregivers(Elsevier, 2018) Winger, Joseph G.; Rand, Kevin L.; Hanna, Nasser; Jalal, Shadia I.; Einhorn, Lawrence H.; Birdas, Thomas J.; Ceppa, DuyKhanh P.; Kesler, Kenneth A.; Champion, Victoria L.; Mosher, Catherine E.; Psychology, School of ScienceContext Little research has explored coping skills practice in relation to symptom outcomes in psychosocial interventions for cancer patients and their family caregivers. Objectives To examine associations of coping skills practice to symptom change in a telephone symptom management (TSM) intervention delivered concurrently to lung cancer patients and their caregivers. Methods This study was a secondary analysis of a randomized pilot trial. Data were examined from patient-caregiver dyads (n=51 dyads) that were randomized to the TSM intervention. Guided by social cognitive theory, TSM involved four weekly sessions where dyads were taught coping skills including: a mindfulness exercise, guided imagery, pursed lips breathing, cognitive restructuring, problem solving, emotion-focused coping, and assertive communication. Symptoms were assessed, including patient and caregiver psychological distress and patient pain interference, fatigue interference, and distress related to breathlessness. Multiple regression analyses examined associations of coping skills practice during the intervention to symptoms at 6 weeks post-intervention. Results For patients, greater practice of assertive communication was associated with less pain interference (β=-0.45, p=0.02) and psychological distress (β=-0.36, p=0.047); for caregivers, greater practice of guided imagery was associated with less psychological distress (β=-0.30, p=0.01). Unexpectedly, for patients, greater practice of a mindfulness exercise was associated with higher pain (β=0.47, p=0.07) and fatigue interference (β=0.49, p=0.04); greater practice of problem solving was associated with higher distress related to breathlessness (β=0.56, p=0.01) and psychological distress (β=0.36, p=0.08). Conclusion Findings suggest the effectiveness of TSM may have been reduced by competing effects of certain coping skills. Future interventions should consider focusing on assertive communication training for patients and guided imagery for caregivers.Item Coping with physical and psychological symptoms: a qualitative study of advanced lung cancer patients and their family caregivers(Springer-Verlag, 2015-07) Mosher, Catherine E.; Ott, Mary A.; Hanna, Nasser; Jalal, Shadia I.; Champion, Victoria L.; Department of Psychology, School of SciencePURPOSE: Advanced lung cancer patients have high rates of multiple physical and psychological symptoms, and many of their family caregivers experience significant distress. However, little is known about strategies that these patients and their family caregivers employ to cope with physical and psychological symptoms. This study aimed to identify strategies for coping with various physical and psychological symptoms among advanced, symptomatic lung cancer patients and their primary family caregivers. METHODS: Patients identified their primary family caregiver. Individual semi-structured qualitative interviews were conducted with 21 advanced, symptomatic lung cancer patients and primary family caregivers. Thematic analysis of interview data was framed by stress and coping theory. RESULTS: Patients and caregivers reported maintaining a normal routine and turning to family and friends for support with symptom management, which often varied in its effectiveness. Whereas support from health-care professionals and complementary and alternative medicine were viewed favorably, reactions to Internet and in-person support groups were mixed due to the tragic nature of participants' stories. Several cognitive coping strategies were frequently reported (i.e., changing expectations, maintaining positivity, and avoiding illness-related thoughts) as well as religious coping strategies. CONCLUSIONS: Results suggest that advanced lung cancer patients and caregivers may be more receptive to cognitive and religious approaches to symptom management and less receptive to peer support. Interventions should address the perceived effectiveness of support from family and friends.