Results of IMPRESS, a lung cancer study presented at the European Society of Medical Oncology in Madrid last week, suggest that the common practice of continuing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) beyond disease progression is misguided, and needlessly expensive.
“IMPRESS is not so impressive,” reported study investigator Tony Mok of the Chinese University, Hong Kong. At first glance, the idea of continuing TKIs beyond progression is counter intuitive; after all, disease progression indicates that the patient has developed resistance to the therapy. “Almost all patients with an initial response to an EGFR TKI eventually develop acquired resistance,” said Dr Mok.
However, as a number of past investigations have suggested, stopping these targeted agents after disease progression can actually make matters worse due to the so-called, flare phenomenon, whereby the tumor comes roaring back to life after treatment discontinuation, rather than continuing to exhibit the indolent growth of treatment-resistant tumor cells.
In order to establish a treatment standard in this setting, IMPRESS recruited 265 patients with non-small cell lung cancer who were experiencing disease progression after treatment with AstraZeneca’s TKI Iressa (gefitinib). Patients were randomised to treatment with gefitinib plus cisplatin and pemetrexed, or the doublet alone.
Dismal PFS results
The primary endpoint for the study was progression-free survival (PFS). Unfortunately, the results from IMPRESS were dismal. The response rates for the two patient cohorts were 31.6% for the TKI regimen versus 34.1% for the doublet alone. “No difference whatsoever,” observed Dr Mok. As for median PFS, both study arms showed disease progression at 5.4 months.
“Continuation of a TKI is no longer an acceptable practice once the patient has progressed,” Dr Mok concluded. “They should just go on to chemo at this point.”
During the press conference where IMPRESS results were first reported, it was asked if Dr Mok’s practice-changing recommendation should be extended to the other TKI, Roche’s Tarceva (erlotinib). “I think there is no difference between the two first-generation TKIs. So yes, I think this observation applies to erlotinib as well.”
Dr Mok did go on to suggest that despite this negative finding, there might be some positive effects.
“There is a financial implication here, for the patient, and the society at large, because continuing a TKI beyond progression is an ongoing practice, and to this point there has been no treatment standard. Patients are recommended to continue treatment and so they, or the system has to pay for it. Hopefully these results will set a new standard.”