Le sorafenib en troisième et quatrième ligne des CBNPC de stade IV : une étude de phase III.

Sorafenib is a multikinase inhibitor that acts on multiple targets including VEGF. It is registered for the treatment of renal cancer and hepatocellular carcinoma. It has been the subject of several studies in Thoracic Oncology including two Phase II studies in non-small lung cancer cells in the second and third line. The Phase III study MISSION (Monotherapy administration of Sorafenib in patients with nOn-small-cell lung cancer) aims to compare the efficacy of sorafenib combined with best comfort care (BSC) to BSC and placebo in patients treated third or fourth line for lung cancer non-small cell non-squamous. This is a major international multi-center study, industrial promotion.

Results

In total, 703 patients were randomized. The characteristics of patients in both groups were similar. Around 55 to 45% of patients were treated respectively in third and fourth line. 

Survival was similar in the two arms (8.2 vs. 8.3 months).

Progression-free survival was significantly longer (2.8 vs 1.4 months).

Finally, 17 patients respectively sorafenib arm and the placebo arm 3 patients were in partial response. Well 148 and 84 were stable.

It is interesting that 154 patients in the experimental group and 198 in the placebo group received at least one further processing line.

A biomarker research was possible in about half of patients:

• Forty-four patients sorafenib arm and the placebo arm 45 had an EGFR mutation. Overall survival of patients in the sorafenib arm was significantly longer than that in the placebo arm (13.9 vs 6.5 months).  
• Thirty four patients in each group had a KRAS mutation: PFS of patients treated with sorafenib was significantly longer, but not survival.

Side effects were significantly increased in the experimental arm, including 55% vs. 6% of hand-foot syndrome, including 16% grade 3 in the experimental arm, 40 vs. 12% of rash or desquamation, 36 vs. 27% fatigue 35 vs 12% diarrhea etc.

This study is negative for its primary purpose, although sorafenib causes, compared to placebo, a significant increase, but modest in PFS and response rate. A significant benefit is nevertheless observed in patients with activating mutations of EGFR. These data are not sufficient, however, to make an alternative therapy sorafenib in third and fourth line. Let us remember also that this study covers more than 700 patients is probably one of the first studies of this size that is available in the third or fourth line of patients with lung cancer non-small cell stage IV.