OA23.07 Analysis of Outcomes in US IRESSA Clinical Access Program (ICAP) Patients on Gefitinib for More Than 10 Years

Abstract

In 2011, following gefitinib (IRESSA®) NDA voluntary withdrawal, US patients benefiting from gefitinib were eligible to continue gefitinib through the IRESSA Clinical Access Program (ICAP), an IRB-approved protocol. A subset of ICAP investigators subsequently collected additional retrospective data on their ICAP patients through another IRB-approved project (“chart-review subset”). For all enrolled ICAP patients, demographic and serious adverse event (SAE) reports were reviewed. All ICAP investigators were invited to participate in chart review; 47 accepted and collected data on patient/tumor characteristics and safety/tolerability of prolonged gefitinib therapy among their 79 ICAP patients. Across 137 US sites, 191 patients enrolled in ICAP. As of September 2016, 75 (39%) remain on gefitinib; discontinuations were due to progression (36%), death (34%), AEs (13%), or other (17%). Sixty-four (34%) patients reported 162 SAEs; 5 (2.6%) patients had 12 SAEs considered to be gefitinib-related by investigators. The chart-review subset included 79 (41%) patients with median age of 69 years at ICAP enrollment, who were predominantly female (70%) and white (84%); 95% had a confirmed NSCLC diagnosis. Due to the evolving understanding of genetic mutations in NSCLC at the time of gefitinib initiation, the majority of patients (79%) never had EGFR sequencing performed. Although tissue is not available for EGFR status confirmation, we assume these patients are nearly exclusively EGFR mutation-positive. Median total length of gefitinib was 11.1 years (6.5-15.1; Table). Long-term gefitinib was well-tolerated; 5% discontinued due to a gefitinib-related AE. Ten-year survival rate from first-ever initiation of gefitinib was 86% and 15-year was 59%.TableGefitinib treatment patterns and tolerability among ICAP chart-review patientsParameter n, %Observed Population (N=79)Total time on gefitinib, prior to and during ICAPMedian duration, y, range11.1 (6.5-15.1)Prior to ICAPMedian duration, y, range7.8 (5.4-10.9)Starting dose 250 mg/day67 (84.8)No dose changes due to AEs75 (94.9)During ICAPMedian duration, y, range3.5 (0.04-4.7)Dose: 250 mg/day76 (96.2)Treatment-related AEs Grade 1-2 Grade ≥3 Grade unknown13 (16.5) 1 (1.3) 2 (2.5)Dose reductions due to treatment-related AEs1 (1.3)Discontinuations due to treatment-related AEs4 (5.1)Discontinuations due to progressive disease11 (28.9) Open table in a new tab The majority of this subset of patients who participated in ICAP based on long-term clinical benefit from gefitinib continue to do well with gefitinib, demonstrating good tolerance of therapy and survival for a median duration of more than 10 years.