GefitinibEdit

Gefitinib is a targeted cancer medicine that blocks a specific signaling pathway linked to the growth and survival of certain tumors. Sold under the brand name Iressa and developed by AstraZeneca, gefitinib is a small-molecule inhibitor that acts on the epidermal growth factor receptor (EGFR). By interrupting EGFR-driven signaling, the drug aims to slow tumor growth and, in some cases, shrink tumors in patients with non-small cell lung cancer (NSCLC) whose cancers depend on this pathway. Gefitinib is one of several drugs in the broader class of tyrosine kinase inhibitors that have shifted cancer treatment away from indiscriminate cytotoxic chemotherapy toward therapies tailored to a tumor’s molecular architecture. Because of its mechanistic focus, gefitinib is most relevant to patients whose tumors show activating changes in EGFR and is less effective in cancers without such drivers.

Gefitinib’s development and use have been shaped by a broader shift toward precision medicine, as clinicians seek to tailor therapy to the biology of the tumor rather than apply a one-size-fits-all approach. The drug’s performance and regulatory history have been the subject of ongoing debate about how best to balance patient access, evidence, and innovation in a system that rewards research and development while demanding clear benefits for patients.

Mechanism of action

Gefitinib is a selective inhibitor of the EGFR tyrosine kinase domain. By binding to the ATP-binding site, it prevents receptor autophosphorylation and downstream signaling through pathways such as the RAF/MEK/ERK and PI3K/AKT cascades, which drive cell proliferation and survival.
Tumors with activating EGFR mutations tend to be more dependent on EGFR signaling, making these cancers more susceptible to EGFR inhibition. In such contexts, gefitinib can produce meaningful tumor responses and disease stabilization.
In tumors lacking EGFR activation, clinical benefit is generally limited, highlighting the importance of molecular testing and patient selection in real-world use.

Medical uses

Gefitinib is used primarily for NSCLC in patients whose tumors harbor activating EGFR alterations. In practice, this biomarker-driven approach means testing tumor tissue for EGFR mutations before or during treatment planning.
The drug is typically administered orally as a once-daily tablet. It may be used after progression on prior therapies or, in some settings, as a frontline option for select patients whose disease biology predicts responsiveness.
Across different regulatory regimes, gefitinib’s indications and monitoring requirements have varied, reflecting evolving evidence about which patients benefit most and how to manage adverse effects such as rash, diarrhea, and changes in liver function.

History and regulation

Gefitinib was developed by AstraZeneca and marketed as Iressa in several markets. The initial approval in some jurisdictions was based on surrogate measures of activity, such as tumor response rates, in patients with advanced NSCLC.
In the United States, gefitinib received accelerated approval in the early 2000s for NSCLC after prior chemotherapy but was later withdrawn from the market after confirmatory trials failed to demonstrate a clear improvement in overall survival. This sequence—rapid approval followed by withdrawal—generated significant controversy about the balance between encouraging innovation and ensuring patient benefit.
In other regions, regulatory agencies and professional guidelines continued to evaluate gefitinib, particularly in the subset of patients whose tumors showed activating EGFR mutations. The trajectory of use has reflected a broader shift toward biomarker-guided therapy and post-market data to confirm real-world benefit.
The debate surrounding gefitinib has featured discussions about regulatory processes (such as accelerated approvals and post-marketing requirements), the responsibilities of pharmaceutical companies in communicating realistic expectations, and the role of biomarkers in guiding treatment choices. Proponents argue that strong IP protections and flexible regulatory pathways foster innovation and faster access to potentially life-extending therapies, while critics emphasize the need for robust evidence of meaningful, durable benefit and careful pricing.

Controversies and debates

Evidence versus speed: Supporters of accelerated approvals contend that allowing earlier access to potentially life-extending therapies can be warranted in serious diseases, provided there is rigorous post-approval study and vigilant monitoring. Critics argue that approvals heavily reliant on surrogate endpoints can expose patients to uncertain benefits and undisclosed risks.
Biomarker-driven use: The case of gefitinib helped spotlight the importance of molecular testing. Advocates emphasize that identifying EGFR mutations ensures that patients most likely to benefit receive the drug, aligning with a broader market-based incentive to develop diagnostics alongside targeted therapies. Detractors worry that access to testing and the cost of companion diagnostics can become bottlenecks in care.
Pricing and access: High drug prices and the economics of oncology care are perennial points of contention. Proponents of market-driven models contend that strong intellectual property rights are essential to recoup R&D investments and fund future innovations. Critics caution that excessive prices limit access and can burden patients and health systems, especially where payment decisions rest on uncertain marginal gains.
Marketing practices and information flow: In the past, debates about how products like gefitinib were presented to clinicians highlighted tensions between timely information about new therapies and the risk of overstatement of benefits. The right balance, critics say, rests on independent evidence synthesis and transparent communication about both benefits and risks.

Economics and access

Gefitinib illustrates the broader economics of targeted cancer therapies, where development costs are high and the potential for meaningful benefit is concentrated in a subset of patients. Economic arguments for strong intellectual property protections are tied to the premise that patents and market exclusivity incentivize innovation and the development of companion diagnostics.
Access considerations include drug licensing, reimbursement decisions, and the availability of molecular testing infrastructure. A market with clear, evidence-based indications and appropriate pricing can support ongoing R&D while still aiming to deliver value to patients and payers.