IressaEdit
Gefitinib, marketed as Iressa, is a targeted cancer therapy classified as a selective inhibitor of the epidermal growth factor receptor tyrosine kinase. By blocking the ATP-binding site of the EGFR enzyme, gefitinib interrupts signaling pathways that promote tumor cell growth and survival, particularly in certain forms of lung cancer. The drug is most closely associated with non-small cell lung cancer ([non-small cell lung cancer|NSCLC]), where tumor dependence on EGFR signaling can be exploited in treatment. Gefitinib’s development and regulatory journey have become a touchstone in debates about rapid access to new targeted medicines, biomarker-driven therapy, and the economics of cancer care. The compound is part of the broader family of tyrosine kinase inhibitors and has been studied in relation to other EGFR-driven malignancies as well. Zeneca developed gefitinib, with the program later brought into the AstraZeneca portfolio.
In the landscape of modern oncology, gefitinib exemplifies how treatment can be tailored to the molecular profile of a tumor. The likelihood of response is higher in tumors with activating mutations in the epidermal growth factor receptor gene, such as certain exon 19 deletions and the L858R substitution. Clinical practice has increasingly emphasized testing for these EGFR mutations to identify patients most likely to benefit from EGFR-targeted therapy. The discussion around gefitinib is therefore inseparable from broader questions about access to biomarker testing and the appropriate use of expensive targeted therapies in health systems with finite resources.
History and development
Gefitinib emerged from early work on targeted inhibition of growth factor signaling in cancer. As a first-in-class EGFR tyrosine kinase inhibitor, it was positioned to provide a more precise alternative to broad-spectrum chemotherapies for patients whose tumors exhibited dependence on EGFR-driven signaling. The initial regulatory path was shaped by the desire to bring a therapy to patients with limited options, but also by the need to demonstrate meaningful clinical benefit beyond response rates. The drug’s trajectory has been closely watched by policymakers, clinicians, and patients as a case study in balancing innovation with proven, durable outcomes. FDA oversight and the results of multinational trials have driven shifts in how such therapies are approved and labeled. The Iressa program intersected with discussions about companion diagnostics, since eligibility in many settings depended on the presence of activating EGFR mutations in a patient’s tumor. The story includes collaboration and competition between pharmaceutical development, regulatory review, and clinical practice guidelines.
Medical uses and regulatory status
Gefitinib was first approved for NSCLC in certain jurisdictions based on early activity signals in patients who had progressed after prior chemotherapy. In the United States, the initial approval and subsequent changes to the labeling prompted ongoing debate about the strength of evidence needed to justify broad use of a targeted agent. A pivotal phase III trial, the International Study of Gefitinib in Lung Cancer (ISEL), did not demonstrate a survival advantage across the overall study population, which tempered enthusiasm for widespread use. This outcome influenced regulatory authorities to recalibrate labeling and usage policies, highlighting a preference for demonstrated overall survival benefit and well-characterized risk–benefit profiles.
Over time, the regulatory emphasis gravitated toward tumors harboring activating EGFR mutations. In those contexts, gefitinib received renewed attention and, in some jurisdictions, authorization for use as first-line therapy in patients with metastatic NSCLC whose tumors carry these mutations. The move toward mutation-directed therapy reflects a broader policy and clinical shift toward precision medicine, where treatments are matched to a tumor’s molecular drivers. The role of companion diagnostic testing is central to this approach, and the regulatory framework increasingly supports biomarker-based patient selection. See also EGFR mutations and biomarker testing for related context.
Adverse effects associated with gefitinib range from skin rashes and diarrhea to more serious risks such as hepatotoxicity and, in rare cases, interstitial lung disease. These safety considerations factor into decisions about patient selection, monitoring, and risk mitigation. The balance of benefit and risk can vary by patient characteristics, tumor biology, and the availability of alternative treatments. See also interstitial lung disease, rash (medical), and hepatotoxicity for more on safety profiles in this class of drugs.
Controversies and debates
The gefitinib experience is often cited in debates about how to regulate, price, and deploy targeted cancer therapies. Key points of controversy include:
Evidence thresholds and approval speed: Proponents of rapid access argued that patients with limited options should benefit from promising therapies while awaiting longer-term data. Critics contended that approvals based on surrogate endpoints or early activity could expose patients to uncertain survival benefits and avoidable toxicity. The ISEL results reinforced the view that robust, hard outcomes matter for policy and practice. See also ISEL trial.
Biomarker-driven treatment and testing access: The shift to mutation-driven use of gefitinib underscores the importance of reliable EGFR mutations testing. Debates persist about who bears the cost of testing, how quickly testing can be implemented across health systems, and how to ensure appropriate patient selection to maximize value. See also EGFR mutations and biomarker testing.
Cost, value, and access: As a targeted therapy with substantial price points in many markets, gefitinib has been at the center of discussions about price, reimbursement, and cost-effectiveness. Lawmakers and payers have debated how to balance incentivizing innovation with ensuring sustainable access to life-extending treatments for patients with NSCLC. See also drug pricing and healthcare economics for broader context.
First-line use versus later lines: The question of when to deploy gefitinib—early in disease for mutation-positive tumors versus after chemotherapy failure—has been a matter of clinical and policy debate. The emergence of other EGFR inhibitors and ongoing comparative trials also shapes how clinicians weigh gefitinib against alternatives. See also EGFR inhibitors and comparative effectiveness.
Safety concerns and risk communication: The potential for serious adverse events, such as interstitial lung disease, necessitates careful patient counseling and monitoring. Proponents argue for clear, evidence-based risk communication and post-market surveillance; detractors worry about over-cautious labeling that could limit access to beneficial therapy. See also drug safety.