Dataset Information

Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis: Experience from 92 Sites in an Open-Label US Expanded Access Program.

ABSTRACT: INTRODUCTION:In phase 3 clinical trials, pirfenidone significantly slowed disease progression with a well-defined and medically manageable safety profile in patients with idiopathic pulmonary fibrosis (IPF). This study examined safety events related to pirfenidone in patients with IPF in an expanded access program in the US. METHODS:The Expanded Access Program allowed patients with IPF access to pirfenidone prior to US Food and Drug Administration approval. Patients had an IPF diagnosis including a definite or possible usual interstitial pneumonia (UIP) pattern, predicted forced vital capacity ?50%, and predicted diffusing capacity for carbon monoxide ?30%. Clinical laboratory data and adverse drug reactions (ADRs) deemed causally related to pirfenidone were analyzed using descriptive summary statistics. RESULTS:Of the 1620 patients treated, 1221 (75.4%) completed the program: 66.5% had definite UIP, and 33.2% had possible UIP. Mean (SD) pirfenidone exposure was 22.8 (9.6) weeks, and mean (SD) daily dose during the course of treatment was 2058.7 (399.2) mg. ADRs occurred in 64.9% of patients: 3.3% were severe and 0.2% life threatening. The most common ADRs were nausea (22.6%) and fatigue (19.6%); 13.0% of patients discontinued due to ADRs. Serious ADRs occurred in 24 patients (1.5%), which were primarily related to elevated liver function enzymes (ten patients, 0.6%). No ADRs led to death. CONCLUSIONS:In this open-label study of 1620 patients with IPF, including those with possible UIP, the safety profile of pirfenidone was consistent with that of earlier clinical trials, and no new safety signals were identified. NCT02141087. FUNDING:Genentech, Inc., a member of the Roche group.

SUBMITTER: Lancaster L

PROVIDER: S-EPMC6964201 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis: Experience from 92 Sites in an Open-Label US Expanded Access Program.

Lancaster Lisa L Morrison Lake L Auais Alexander A Ding Beiying B Iqbal Ahmar A Polman Boris B Flaherty Kevin R KR

Pulmonary therapy 20170906 2

<h4>Introduction</h4>In phase 3 clinical trials, pirfenidone significantly slowed disease progression with a well-defined and medically manageable safety profile in patients with idiopathic pulmonary fibrosis (IPF). This study examined safety events related to pirfenidone in patients with IPF in an expanded access program in the US.<h4>Methods</h4>The Expanded Access Program allowed patients with IPF access to pirfenidone prior to US Food and Drug Administration approval. Patients had an IPF dia ...[more]

PMID: 32026347

Similar Datasets

Project description:IntroductionPIPF-002 was a phase 2, multicenter, open-label study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) or other types of pulmonary fibrosis (PF). PIPF-002 terminated after pirfenidone became commercially available in the United States. The goal of PIPF-002 was to characterize the long-term safety of pirfenidone in these patients.MethodsBetween August 2003 and September 2006, 83 patients (IPF: 81, PF: 2) enrolled. Patients received pirfenidone in three divided doses daily, with the maintenance dose and schedule determined by enrollment group assignment. Treatment continued until patient withdrawal or study termination (2015). Treatment-emergent adverse events (TEAEs) were assessed by descriptive statistics.ResultsAt baseline, median age was 70 years, mean percent predicted forced vital capacity was 67.7%, 33.7% of patients had cardiac disorders, 51.8% had gastroesophageal reflux disease, and 63.9% were receiving concomitant prednisone. Median pirfenidone dose and exposure duration were 2400 mg/day and 3.0 years, respectively. Cumulative total exposure was 279.7 patient-exposure years (PEY). Most patients (98.8%) reported ≥ 1 TEAE, with an overall incidence rate of 460.5 per 100 PEY. The most frequent TEAEs (incidence rate per 100 PEY) were nausea (23.6), IPF progression (16.1), fatigue (11.8), dyspnea (11.4), upper respiratory tract infection (11.4), and cough (10.7). Serious TEAEs were reported in 49 patients; the most frequent serious TEAEs were IPF progression and pneumonia. The most common reason for discontinuation was TEAEs (35 patients; 12.5 patients per 100 PEY), most frequently IPF progression and nausea. Overall, 21 patients died (7.5 per 100 PEY); 16 deaths were IPF-related.ConclusionsLong-term safety and tolerability of pirfenidone findings in this study were consistent with the known safety profile of pirfenidone; no new safety signals were identified. These data support the continued use of pirfenidone in patients with IPF.FundingF. Hoffmann-La Roche Ltd./Genentech, Inc.Trial registrationClinicalTrials.gov identifier, NCT00080223. Plain language summary available for this article.

Project description:BackgroundThe incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP.MethodsEligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician's discretion.ResultsBetween April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5-41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%]).ConclusionsResults from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.

Project description:This open-label, multicenter study was designed to allow access to vemurafenib for patients with metastatic melanoma, bridging the time between end of enrollment in the phase III registration trial (December 2010) and commercial availability following US Food and Drug Administration approval of vemurafenib for the treatment of unresectable or metastatic BRAF-mutated melanoma (August 2011).Eligible patients had metastatic melanoma with a BRAF mutation (detected by the cobas 4800 BRAF V600 Mutation Test). Unlike previous vemurafenib trials, patients with poor performance status (PS) and treated brain metastases were permitted. Enrolled patients received oral vemurafenib 960 mg twice daily.Of 374 patients enrolled at 29 US sites (December 2010 to October 2011), 371 patients received vemurafenib and were followed up for a median of 2.8 months (the study had a prespecified end upon vemurafenib approval and commercial availability). At baseline, most patients (75%) had stage M1c disease, and 19% had an Eastern Cooperative Oncology Group PS of 2 or 3; 72% of patients had received prior systemic therapy for metastatic melanoma, 27% received prior ipilimumab, and 29% radiotherapy for prior brain metastases. Because reassessment data to confirm response were not available for most patients, point estimates of objective response rate (ORR) are reported. Among 241 efficacy-evaluable patients, the ORR was 54% (median time to response, 1.9 months). The ORR in non-central nervous system sites in patients with previously treated brain metastases (n = 68) was 53%. The ORR in prior ipilimumab-treated patients (n = 68) was 52%. For patients with PS of 0 or 1 (n = 210) and 2 or 3 (n = 31), the ORRs were 55%, and 42%, respectively. The safety profile observed was consistent with that reported in previous studies. The number of patients with grade 3 or 4 treatment-related adverse events was higher in patients with PS 2 or 3 than in those with PS 0 or 1 (10% vs. 5%, respectively). Adverse events requiring a dose reduction (at least 1 level) occurred in 11% of patients, and 9 patients (2%) experienced events leading to vemurafenib withdrawal, including 2 with repeated QT interval prolongation.This study confirmed the established rapid and high tumor response rate achievable with vemurafenib in BRAF mutation-positive metastatic melanoma. Several groups not included in previous studies, including patients with previously treated brain metastases, Eastern Cooperative Oncology Group PS 2 to 3, or previous ipilimumab treatment had benefitted from vemurafenib similar to the overall population. No new safety signals were detected.

Project description:BACKGROUND:In the phase III ALSYMPCA trial, metastatic castration-resistant prostate cancer (mCRPC) patients had few prior life-prolonging therapies. Following ALSYMPCA, which demonstrated radium-223 survival benefit, and before radium-223 U.S. commercial availability, an expanded access program (EAP) providing early-access radium-223 allowed life-prolonging therapies in current use. SUBJECTS, MATERIALS, AND METHODS:This phase II, open-label, single-arm, multicenter U.S. EAP (NCT01516762) enrolled patients with symptomatic mCRPC, ?2 bone metastases, and no lung, liver, or brain metastases. Patients received radium-223 55 kBq/kg intravenously every 4 weeks × 6. Primary outcomes were acute and long-term safety. Additional analyses were done by number of radium-223 injections, and prior or concomitant abiraterone or enzalutamide use. RESULTS:Of 252 patients, 184 received radium-223: 165/184 (90%) had Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 183 (99%) had prior systemic anticancer therapy. Treatment-related adverse events occurred in 93/184 (51%) patients during treatment and 11 (6%) during follow-up. Median overall survival was 17 months, with 134/184 (73%) patients censored because of short follow-up due to radium-223 approval. In post hoc analyses, patients with ?3 prior anticancer medications, baseline ECOG performance status ?2, and lower baseline hemoglobin were less likely to receive 5-6 radium-223 injections and unlikely to benefit from radium-223. Radium-223 was well tolerated regardless of concurrent or prior abiraterone or enzalutamide. CONCLUSION:Radium-223 was well tolerated, with no new safety concerns; safety was maintained with abiraterone or enzalutamide. Patients with more advanced disease were less likely to benefit from radium-223. Clinicians should consider baseline characteristics and therapy sequence for greatest clinical value. IMPLICATIONS FOR PRACTICE:In this phase II U.S. expanded access program, radium-223 was well tolerated, with a median overall survival of 17 months in metastatic castration-resistant prostate cancer patients. In post hoc analyses, radium-223 was safe regardless of concurrent abiraterone or enzalutamide, and median overall survival appeared longer when radium-223 was used earlier in patients with less prior treatment. Patients with more advanced disease were less likely to benefit from radium-223. Clinicians should consider baseline clinical characteristics and therapy sequence to provide the greatest clinical value to patients.

Dataset Information

Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis: Experience from 92 Sites in an Open-Label US Expanded Access Program.

Publications

Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis: Experience from 92 Sites in an Open-Label US Expanded Access Program.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets