Gefitinib: a second look. Non-small cell lung cancer: still very disappointing

(1) In patients with non-small cell lung cancer, whatever the stage, the benefits of cytotoxic chemotherapy are limited. There is no consensus second-line chemotherapy after failure of first-line platinum-based chemotherapy; (2) Gefitinib is an EGF (epidermal growth factor) receptor inhibitor available in France for named-patient compassionate treatment of non-small cell lung cancer when first-line chemotherapy fails; (3) When we examined gefitinib in this indication in 2004 and 2006, we were unable to reach a firm conclusion on its risk-benefit balance; (4) Preliminary analysis of a placebo-controlled trial in 255 patients unexpectedly showed that adding gefitinib to chemoradiotherapy followed by docetaxel shortened median survival time, from 35 months with placebo to only 23 months (p=0.013). Another trial in 603 patients showed no difference in survival between patients receiving 6 cycles of platinum-based chemotherapy versus patients receiving 3 cycles of the same chemotherapy followed by gefinitib[sic]; (5) A few rather unreliable data suggest that gefitinib may be more effective in certain subgroups, but there are no reports of relevant prospective trials of sufficient size and with sufficient follow-up; (6) In second-line treatment, there are 4 unblinded trials versus docetaxel. One trial in 1466 patients suggested that gefitinib was "non-inferior" to docetaxel, but this non-inferiority was not confirmed in another trial in 489 patients. Half of the patients enrolled in these trials died within 8 months. Two other trials in 161 and 141 patients showed no difference in survival between patients treated with gefinitib[sic] and those treated with docetaxel; (7) The adverse effects observed in these trials confirmed what was already known about gefitinib: epithelial toxicity frequently leads to potentially severe skin rash and diarrhoea, as well as rare but life-threatening interstitial pneumonia; (8) In practice, there is no reason to use gefitinib in non-small cell lung cancer, except perhaps when there are no other available options and in a subgroup of patients who might benefit and who agree to participate in a comparative trial.