english.prescrire.org > Spotlight > Archives : 2009 > Gefitinib in non-small cell lung cancer: still very disappointing

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Gefitinib in non-small cell lung cancer:
still very disappointing

FEATURED REVIEW In patients with non-small cell lung cancer, there is no firm evidence that gefitinib is effective as a first-line treatment. Similarly, it has not been demonstrated that gefitinib is as effective as docetaxel in second-line treatment. Gefitinib has severe adverse effects, including interstitial pneumonia.
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Abstract

  • 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.
  • 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.
  • When we examined gefitinib in this indication in 2004 and 2006, we were unable to reach a firm conclusion on its risk-benefit balance.
  • 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.
  • 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.
  • 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 and those treated with docetaxel.
  • 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.