Global Expanded Access Program Research Articles

Report of an international expanded access program of imatinib in adults with Philadelphia chromosome positive leukemias

BackgroundImatinib is a selective inhibitor of the BCR/ABL tyrosine kinase. The remarkable initial results of the first phase I clinical trial published in 1999 prompted the rapid initiation of large phase II trials. They also generated intense media coverage and significant interest from patients and clinicians and demand for access to imatinib before marketing approval. In response, a worldwide expanded access program (EAP) for imatinib was implemented in May 2000. PatientsIn total, 7380 patients with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia failing prior therapies were enrolled in 106 centers in 34 countries. ResultsTime to progression and overall survival, as well as the safety profile, were similar to those observed in published phase II studies. At the end of the program, patients benefiting from treatment were continued on imatinib therapy by transferring to national health care systems or patient assistance programs. ConclusionThe imatinib EAP successfully provided therapy to patients with CML before marketing approval. The program provides an efficient framework for the development of global EAPs for innovative investigational anticancer agents in patients without a satisfactory therapeutic alternative.

Efficacy and safety of gefitinib in chemo-naive patients with non-small cell lung cancer (NSCLC) in an expanded access program (EAP)

7094 Background: Patients (pts) with advanced NSCLC who cannot tolerate or refuse chemotherapy (CT) have few or no treatment options. The EGFR-TKI gefitinib (Iressa) has antitumor activity and favorable tolerability in pts with recurrent advanced NSCLC. A global EAP made gefitinib available to >37,000 pts with NSCLC who had failed standard treatment or were ineligible for or refused cytotoxic CT. Methods: Retrospective chart review of 1671 pts enrolled at 11 sites in the US EAP identified 198 pts (89 men, 109 women, median age 72.7 y [range 37.8–89.9 y]) who had not received prior CT for advanced NSCLC. Pts received 250 mg/d gefitinib until treatment failure or undue toxicity. Outcomes analyzed included clinical response, survival, and adverse events (AEs). Results: Reasons for enrollment were disease progression (57.6%), CT intolerance (22.2%), significant comorbidity (21.7%), and CT refusal (21%). Predominant (66%) histology was adenocarcinoma, 16.2% with bronchioloalveolar subtype: 186 pts (93.9%) had stage III/IV disease, 3 (1.5%) were stage I/II, and 9 (4.5%) had no staging data recorded. Fifty-six (28.3%) patients had ECOG performance status (PS) ≥2. Although PS was not recorded for 69 (34.8%) pts, at enrollment 60% were nonambulatory, 15.2% required oxygen, and 4% were in a hospice. Median survival was 6 months (95% CI, 5–8 mo); estimated 1-year survival rate was 29.7% (95% CI, 22.1–37.3%). In 142 (72.2%) pts with ≥1 imaging study postenrollment, complete, partial, and stable response rates were 0.7%, 5.6%, and 40.6%, respectively. Most common AEs were diarrhea (31.3%), rash (31.3%), asthenia (15.7%), anorexia (11.6%), and nausea (11.1%). Mean treatment duration was 4.7 months (range 0.1–26 mo). Post-EAP treatment data were available for 157 (79.3%) pts: 36 (22.9%) of this group went on to further treatment, 25 received CT, and 11 received radiation therapy. Conclusions: Oral gefitinib was well tolerated and effective in this unselected population of chemo-naive pts with NSCLC who were unsuitable for or refused CT. Median and 1-year survival were significantly better than with best supportive care alone and similar to CT, with substantially less toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, Ligand Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck, Pfizer Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Genta, Ligand, Pfizer AstraZeneca Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly