• In the Phase III IMPRESS trial (n = 265), the continuation of gefitinib with chemotherapy did not improve PFS, response rate or disease control rate compared to chemotherapy alone in patients who had experienced disease progression on first-line gefitinib.
• The Phase II ASPIRATION study (n = 207) demonstrated the feasibility of the continuation of erlotinib beyond disease progression.

The IMPRESS study evaluated the utility of continuing a biologic agent after disease progression, a concept that has been tested in other tumor types, namely with trastuzumab in breast cancer and bevacizumab in colorectal cancer. In EGFR-mutant lung cancer, there has been concern that patients who initially respond to a TKI may experience disease flare when the EGFR TKI is stopped abruptly and patients are switched to chemotherapy after disease progression. Although this study did not demonstrate a benefit with continuation of treatment, it did not rule out the possibility that occasional patients might suffer from tumor flare, and Dr Spigel’s approach in this situation is to continue the TKI until the patient begins to improve with chemotherapy.

Another data set, the ASPIRATION trial out of Asia, demonstrated the feasibility of continuing an EGFR TKI in highly selected patients who are clinically stable but who have objective evidence of disease progression.

Currently these approaches seem most relevant for patients without T790M tumor mutations who are not eligible for second-generation EGFR TKIs and for whom chemotherapy is often used.