FDA analysis of ECOG performance status and safety outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12024-12024 ◽  
Author(s):  
Harpreet Singh ◽  
Yutao Gong ◽  
Pourab Roy ◽  
Bellinda King-Kallimanis ◽  
Vishal Bhatnagar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Cumulative Incidence ◽  
Performance Status ◽  
Poor Performance ◽  
Treatment Discontinuation ◽  
Dropout Rates ◽  
Poor Performance Status ◽  
Ecog Performance Status ◽  
Eligibility Criteria

12024 Background: Patients with poor performance status are often excluded from clinical trials. The FDA has published several guidances on modernizing oncology clinical trial eligibility criteria to more accurately reflect the patient population. Many patients receiving novel oncology therapeutics are heavily pretreated, and often have comorbidities, organ dysfunction, and frailty syndromes. Little is known about the safety of novel therapeutics in patients with poor performance status. Methods: Data from six randomized trials (n=4465) leading to registration for several solid tumor and malignant hematologic cancers, including multiple therapeutic mechanisms of action, such as EGFR TKI’s, immune checkpoint inhibitors (ICI), and chemotherapy, were pooled. Cumulative incidence of Grade 3-5 adverse events and serious adverse events at Days 30, 90, and 180 were evaluated based on ECOG 0-2. Rates of treatment discontinuation by ECOG was also examined. Results: Cumulative incidence of toxicity events at days 30, 90, and 180 are shown in Table. Patient dropout rates due to death were 3.9%, 6.7%, and 10.9%; dropout rates due to disease progression were 66.5%, 66.6% and 56.9%; and dropout rates due to reasons other than progression or death were 29.7%, 26.7% and 32.1% for ECOG PS 0, 1 and 2, respectively. Conclusions: This FDA exploratory analysis of safety outcomes in registration trials based on ECOG suggests increasing rates of adverse events and rates of treatment discontinuation due to death with worsening performance status. Discontinuation rates due to disease progression and other reasons did not appear to be worse for ECOG 2 compared to 0-1. These findings were consistent across therapies (targeted therapy, ICI, chemotherapy). All trials in the analysis led to FDA approval, thus inclusion of patients with ECOG 2 did not adversely affect the trial outcome for this set of FDA approved agents. ECOG performance status eligibility criteria should be evaluated and modified on a frequent basis during drug development. Additional analysis of trials which enroll patients with ECOG 2 is needed. [Table: see text]

scholarly journals A pilot study of novel duodenal covered self-expandable metal stent fixation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasuki Hori ◽  
Kazuki Hayashi ◽  
Itaru Naitoh ◽  
Katsuyuki Miyabe ◽  
Makoto Natsume ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Gastric Outlet Obstruction ◽  
Clinical Success ◽  
Performance Status ◽  
Outlet Obstruction ◽  
Poor Performance ◽  
Stent Migration ◽  
Poor Performance Status ◽  
Sems Placement

AbstractMigration of duodenal covered self-expandable metal stents (C-SEMSs) is the main cause of stent dysfunction in patients with malignant gastric outlet obstruction (mGOO). Because endoscopic SEMS placement is frequently selected in patients with poor performance status, we concurrently focused on the safety of the treatment. This pilot study included 15 consecutive patients with mGOO who underwent duodenal partially covered SEMS (PC-SEMS) placement with fixation using an over-the-scope-clip (OTSC). Technical feasibility, clinical success for oral intake estimated by the Gastric Outlet Obstruction Scoring System (GOOSS) score, and adverse events including stent migration were retrospectively assessed. All procedures were successful, and clinical success was achieved in 86.7% (13/15). Mean GOOSS scores were improved from 0.07 to 2.53 after the procedure (P < 0.001). Median survival time was 84 days, and all patients were followed up until death. Stent migration occurred in one case (6.7%) at day 17, which was successfully treated by removal of the migrated PC-SEMS using an enteroscope. For fixation using an OTSC, additional time required for the procedure was 8.9 ± 4.1 min and we did not observe OTSC-associated adverse events. Poor performance status was associated with clinical success (P = 0.03), but we could provide the treatment safely and reduce mGOO symptoms even in patients with poor performance status. In conclusion, duodenal PC-SEMS fixation using an OTSC is feasible for preventing stent migration in patients with mGOO including those with poor performance status.

Feasibility of Duodenal Covered Self-Expandable Metal Stent Fixation: A Pilot Study (With Video)

2021 ◽  
Author(s):  
Yasuki Hori ◽  
Kazuki Hayashi ◽  
Itaru Naitoh ◽  
Katsuyuki Miyabe ◽  
Makoto Natsume ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Gastric Outlet Obstruction ◽  
Clinical Success ◽  
Performance Status ◽  
Outlet Obstruction ◽  
Poor Performance ◽  
Stent Migration ◽  
Poor Performance Status ◽  
Sems Placement

Abstract Migration of duodenal covered self-expandable metal stents (C-SEMSs) is the main cause of stent dysfunction in patients with malignant gastric outlet obstruction (mGOO). Because endoscopic SEMS placement is frequently selected in patients with poor performance status, we concurrently focused on the safety of the treatment. This pilot study included 15 consecutive patients with mGOO who underwent duodenal C-SEMS placement with fixation using an over-the-scope-clip (OTSC). Technical feasibility, clinical success for oral intake estimated by the Gastric Outlet Obstruction Scoring System (GOOSS) score, and adverse events including stent migration were assessed. All procedures were successful, and clinical success was achieved in 86.7% (13/15). Mean GOOSS scores were improved from 0.07 to 2.53 after the procedure (P < 0.001). Stent migration occurred in one case (6.7%) with no other adverse events. For fixation using an OTSC, additional time required for the procedure was 8.9 ± 4.1 minutes. Poor performance status was associated with clinical success (P = 0.03), but we could provide the treatment safely and reduce mGOO symptoms even in patients with poor performance status. In conclusion, duodenal C-SEMS fixation using an OTSC is feasible for preventing stent migration in patients with mGOO including those with poor performance status.

Utilizing Eastern Cooperative Oncology Group (ECOG) performance status scores to prevent harm with chemotherapy at the end of life.

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 146-146
Author(s):  
Eve Newhart ◽  
Beth Karlan ◽  
Rita Shane ◽  
Vipul Patel ◽  
Bradley T. Rosen ◽  
...  
Keyword(s):  
End Of Life ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Cancer Treatments ◽  
Ecog Performance Status ◽  
Number Of Patients ◽  
Inpatient Settings ◽  
Practice Methods

146 Background: According to ASCO’s “top five” list of non evidence-based cancer treatments and procedures, the use of chemotherapy in solid tumor patients with evidence of poor performance status is at the top of the list. The Dartmouth Atlas report revealed a significant overuse of chemotherapy at the end of life (EOL), and Cedars-Sinai was identified as an outlier with regards to this practice. Methods: Cedars-Sinai’s interdisciplinary cancer quality committee designed a new initiative to eliminate the ineffective administration of chemotherapy. Each patient’s ECOG score, entered by a nurse or physician, was used as an appropriateness screen by pharmacists before they released chemotherapy in both the outpatient and inpatient settings. If a patient did not qualify for chemotherapy based on an ECOG score of 3 or greater, the pharmacist contacted the prescribing oncologist to discuss the case. Ultimately the oncologist had the final say as to whether the patient received chemotherapy. Data was collected on ECOG scores, number of patients screened and identified as being at risk, oncologists’ responses to being notified, and whether chemotherapy was ultimately administered. Results: Available data collected on the % of orders with ECOG scores, since February of 2014 is shown in the Table. Conclusions: Data and conclusions regarding oncologists’ responses to being notified, and whether chemotherapy was ultimately administered, and harm thus prevented, is currently being compiled and will be presented at the conference. [Table: see text]

Outcomes and safety analysis of a phase IB trial of stereotactic body radiotherapy (SBRT) to all sites of oligometastatic non-small cell lung cancer combined with durvalumab and tremelimumab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21212-e21212
Author(s):  
Michael Frederick Bassetti ◽  
Nan Sethakorn ◽  
Joshua Michael Lang ◽  
Jennifer L. Schehr ◽  
Zachery Schultz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Performance Status ◽  
Cohort Analysis ◽  
Median Number ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Grade 3 ◽  
Metastatic Sites

e21212 Background: Combining local ablative and systemic therapies in patients with oligometastatic NSCLC leads to improved overall survival (OS) and progression-free survival (PFS). The potential immunostimulatory effects of ablating all visible disease with SBRT in combination with dual immune checkpoint inhibition has prompted interest, but the toxicity and benefit are unknown. Methods: We conducted a phase Ib study to investigate the safety of SBRT, with doses between 30 and 50 Gy in five fractions to all sites of disease, followed by durvalumab 1500 mg IV in combination with tremelimumab 75 mg IV every 4 weeks x 4 cycles, followed by durvalumab maintenance until progression. Eligible patients had 1-6 extracranial metastatic sites, allowing multiple metastases per location, with all lesions suitable for SBRT, ECOG performance status 0-1, no actionable driver mutation, and no prior immunotherapy. The primary endpoint was safety of this combination. Secondary endpoints include PFS and OS. Dose-limiting toxicities (DLTs) (any Grade ≥ 3 toxicity) were evaluated from the first administration of SBRT until 28 days post start of durvalumab and tremelimumab. Baseline tumor mutational burden, PD-L1 expression on post-SBRT biopsy and circulating tumor cells will be correlated with outcomes. In this first cohort analysis, we assess the safety and outcomes of the first 17 patients. Results: From 2/2018-2/2021, the first 17 pts were enrolled. Characteristics of those enrolled included: median age 68 years, female/male 4/13, squamous/non-squamous 2/15, median number of non-central nervous system (CNS) metastatic sites 2 (1-5), median number of non-CNS metastatic lesions 2 (1-9), CNS involvement 6/17 (35.3%), previous treatment 4/17 (23.5%). DLTs were seen in 2/17 (11.8%) patients; DLTs were autoimmune hepatitis and autoimmune pancreatitis. Most treatment-related adverse events (TRAEs) were grade (G) 1/2. TRAEs included: all TRAEs n = 188, 88.2% (of patients); G 3 n = 17, 29.4%; G 4 n = 1, 5.8%. There were no treatment-related deaths. Five patients discontinued treatment due to grade 3/4 immune related adverse events (IRAE). At a median follow up of 20 months 11/17 (64.7%) patients are alive with 10/17 (58.8%) with no evidence of disease (NED). Six of 17 (35.2%) patients experienced disease progression and 4/17 (23.5%) patients died of disease progression. Median PFS and OS are not yet reached. Conclusions: There were no unexpected safety signals in the cohort of patients enrolled. The incidence of grade ≥ 3 IRAEs is similar to the treatment of advanced NSCLC and no additional toxicity was observed with the addition of SBRT. Clinical outcomes look promising with median OS and PFS not yet reached at 20 months median follow up. The study continues to enroll a second cohort and results will be updated. Clinical trial information: NCT03275597.

Demographics, outcomes, and risk factors for patients (Pts) with sarcoma and COVID-19: A multi-institutional cohort analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11523-11523
Author(s):  
Michael J Wagner ◽  
Matthew Ingham ◽  
Corrie Painter ◽  
Rashmi Chugh ◽  
Jonathan C. Trent ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Endpoint ◽  
Lung Metastases ◽  
Performance Status ◽  
Cohort Analysis ◽  
Poor Performance ◽  
Adverse Outcomes ◽  
Poor Performance Status ◽  
Ecog Performance Status ◽  
Icu Admission

11523 Background: Sarcoma pts often receive aggressive, highly immunosuppressive therapy and may be at high risk for severe COVID-19. Demographics, outcomes and risk factors for pts with sarcoma and COVID-19 are unknown. We aimed to describe the course of COVID-19 in sarcoma pts and to identify factors associated with adverse outcomes. Methods: The COVID-19 and Cancer Consortium (NCT04354701) is an international registry of pts with cancer and COVID-19. Adult pts (≥18 years old) with a diagnosis of sarcoma and laboratory confirmed SARS-CoV-2 were included from 50 participating institutions. Data including demographics, sarcoma diagnosis and treatment, and course of COVID-19 infection were analyzed. Primary outcome was the composite rate of hospitalization or death at 30 days from COVID-19 diagnosis. Secondary outcomes were 30 day all-cause mortality, rate of hospitalization, O2 need, and ICU admission. Descriptive statistics and univariate Fisher tests are reported. Results: From March 17, 2020 to February 6, 2021, N=204 pts were included. Median follow up was 42 days. Median age was 58 years (IQR 43-67). 97 (48%) were male. 30 (15%) had ECOG performance status ≥2. 104 (51%) received cancer treatment, including surgery or radiation, within 3 months of COVID-19 diagnosis. 153 (75%) had active cancer, of whom 34 (22%) had lung metastases. 100 (49%) pts met the composite primary endpoint; 96 (47%) were hospitalized and 18 (9%) died within 30 days from COVID-19 diagnosis. 64 (31%) required oxygen, and 16 (8%) required ICU admission. Primary endpoint rates were similar for pts who received cytotoxic chemotherapy (38/58, 66%) or targeted therapy (16/28, 57%). Pts with higher rates of the primary endpoint included patients ≥60 years old (59% vs 40%, OR 2.04, 95% CI 1.12-3.74, p=0.016), pts with ECOG PS ≥2 vs 0-1 (90% vs 41%, OR 12.2, 95% CI 3.44-66.8, p<0.001), pts receiving any systemic therapy within 3 months of COVID-19 diagnosis (62% vs 39%, OR 2.65, 95% CI 1.43-4.97, p=0.001), and pts with lung metastases (68% vs 42%, OR 2.77, 95% CI 1.19-6.79, p=0.013). Primary endpoint rates were similar across sarcoma subtypes (Table). Conclusions: This is the largest cohort study of pts with sarcoma and COVID-19 to date. Sarcoma pts have high rates of complications from COVID-19. Older patients, those with poor performance status, those recently receiving systemic cancer therapy, and those with lung metastases appear to have worse outcomes.[Table: see text]

Gemcitabine-carboplatin (GCb) versus gemcitabine-oxaliplatin (GemOx) in cisplatin un-fit advanced urothelial carcinoma: Randomized phase II study (COACH Study).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Jae-Lyun Lee ◽  
Bong-Seog Kim ◽  
Ho Yeong Lim ◽  
Hee Jun Kim ◽  
Inkeun Park ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Salvage Chemotherapy ◽  
Comparable Efficacy ◽  
Poor Performance Status ◽  
Hematologic Toxicity ◽  
Ecog Performance Status ◽  
Treatment Naïve ◽  
Visceral Metastases

355 Background: More than half of patients (pts) with advanced urothelial cell carcinoma (UCC) are ineligible for cisplatin because of renal dysfunction or poor performance status. We investigated the activity and safety of first-line gemcitabine-oxaliplatin (GemOx) compared with gemcitabine-carboplatin (GCb) in cisplatin-ineligible pts with advanced UCC. Methods: Treatment naïve, cisplatin-ineligible pts with advanced UCC were randomly assigned to GemOx (gemcitabine 1000 mg/m2, oxliplatin 100 mg/m2 on D1 Q2W) or GCb (gemcitabine 1000 mg/m2 on D1 and 8, carboplatin AUC 4.5 on D1 Q3W) stratified by ECOG performance status (PS) and visceral metastases. The primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Between May 2013 and Mar 2017, 80 pts were enrolled and 79 pts received at least one dose of chemotherapy (39 pts in GCb; 40 pts in GemOx). Median age was 73 years (47-86) and ECOG PS was 2 in 42% of pts and 60% had visceral metastases. Median GFR was 45 ml/min (range 22-108) in GCb and 47 ml/min (range 15-73) in GemOx arm. With median follow-up duration of 37.8 months, all pts were off study treatments. RR were 48.7% and 55.0% in GCb and GemOx, respectively (p = 0.742). Median PFS and OS in GCb and GemOx arm were 5.5 months (95% CI, 4.8-6.2) vs. 4.4 months (95% CI, 2.7-6.1) [HR GemOx/GCb 0.92; p = 0.756] and 9.1 months (95% CI, 5.2-13.0) vs. 11.0 months (95% CI, 6.9-15.0) [HR 0.72; p = 0.194], respectively. The median cycle was 6 (1-10) in GCb and 7 (1-12) in GemOx. Grade 3 leukopenia, neutropenia and fatigue were more common in GCb arm (25.6% vs. 2.5%, p = 0.003; 33.3% vs. 10.0%, p = 0.014; 15.4% vs. 0%, p = 0.012). Dose delay and reduction in GCb and GemOx group were needed in 46.2%, 50.0% and 53.8%, 32.5%, respectively. Salvage chemotherapy after study treatment was offered in 54.3% and 55.9% of patients who experienced PD in GCb and GemOx arm. Conclusions: GemOx has showed comparable efficacy with GCb and favorable hematologic toxicity profile. GemOx may be used as a new option for patients who are not suitable for cisplatin-containing chemotherapy. Clinical trial information: NCT01487915.

Do eligibility criteria restrict access to clinical trials?

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 94-94
Author(s):  
Nessa Stefaniak ◽  
Jennifer Walker ◽  
Monica L. Murphy ◽  
Mishellene McKinney ◽  
Lu Liu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cellular Therapy ◽  
Clinical Pathways ◽  
Point Of Care ◽  
Performance Status ◽  
Poor Performance ◽  
Cancer Center ◽  
Poor Performance Status ◽  
Adoptive Cellular Therapy ◽  
Eligibility Criteria

94 Background: Stringent eligibility criteria may be a barrier to oncology clinical trial enrollment. We examined patients meeting basic trial eligibility criteria defined in a clinical pathway where the trial was not selected, and then performed a thorough review of full trial eligibility. Methods: Locally available trials are embedded into a pathways tool used at the point of care by medical oncologists at a tertiary cancer center. The physician can choose to have the patient fully screened for the recommended trial or bypass it. Patients where the physician bypassed the trial for eleven Phase 2 and 3 solid tumor trials from April 2018 to December 2019 were reviewed for trial eligibility. Basket trials and adoptive cellular therapy trials were excluded. Trials selected for the audit were presented for more than 20 patients and were bypassed in 80% or more cases. For each trial a random set of 20% of cases or a minimum of 15 cases minimum were reviewed. Results: Among the 184 cases reviewed, 149 (81%) were trial ineligible based upon one or more criteria. The most common reasons for patients' ineligibility were the wrong biomarker profile, prior drug treatment, and health conditions including co-morbidities, autoimmune diseases, other cancers and poor performance status. Conclusions: The majority of patients meeting basic eligibility in a clinical pathways system did not meet strict eligibility criteria. This suggests the trials may not be reflective of the needs of the cancer population being treated and may limit the applicability of trial results to the general cancer population. Use of the pathway program to define eligibility is limited by the numerous and nuanced eligibility criteria that cannot be programmed into the pathways system. Clinical trials eligibility criteria and pathway tools need to adapt to the patient population to help advance cancer research. [Table: see text]

scholarly journals Rapid regression of neurological symptoms in patients with metastasised ALK+ lung cancer who are treated with lorlatinib: a report of two cases

2019 ◽  
Vol 12 (7) ◽  
pp. e227299 ◽  
Author(s):  
Huda Gafer ◽  
Quincy de Waard ◽  
Annette Compter ◽  
Michel van den Heuvel
Keyword(s):  
Lung Cancer ◽  
Disease Progression ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Poor Performance ◽  
Neurological Symptoms ◽  
Poor Performance Status ◽  
Third Generation ◽  
Anaplastic Lymphoma ◽  
Almost All

Oral anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) have shown significant benefit in the management of ALK-rearranged non-small cell lung cancer (NSCLC). However, almost all patients will experience disease progression after front-line ALK-TKIs such as crizotinib. Treatment with third generation ALK-TKI lorlatinib can have a significant clinical impact following disease progression, even in patients with a very poor performance status. Here, we review two clinical cases with metastatic ALK-rearranged NSCLC who had pulmonary disease control with first-generation ALK inhibitor. However, disease progressed rapidly in the central nervous system with severe neurological symptoms. Treatment with lorlatinib, a third-generation ALK-TKI, led to a rapid radiological and clinical cerebral response in both patients. Lorlatinib can overcome ALK resistance to crizotinib, and the presented cases suggest a potential role for lorlatinib in patients with rapidly progressive cerebral and leptomeningeal metastases.

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