The Study: Tumor necrosis factor (TNF)-α is effective at killing tumors. Unfortunately it’s also effective at killing humans. Enter TNF-α conjugated to NGR, a peptide that selectively binds to CD13. Why CD13? Because it’s present all over newly formed blood vessels such as, say, those found en masse feeding tumors, and such selection allows the once laze-level tumoricidal doses of TNF-α to be decreased by a factor of 10. Why try it in mesothelioma? Because apparently it’s known to be particularly vascular, even among tumors. That and there’s not much to lose after patients fail pemetrexed/cisplatin. So an international European phase 3 trial gave it a go. 400 patients with relapsed mesothelioma of a variety of histologies all received investigator’s choice of therapy (including supportive care without chemo) + NGR-hTNF at 0·8 μg/m2 versus placebo. The good news was there was no difference in toxicity, which is a big step for therapeutic TNF-α. The bad news was there was no difference in anything, including the primary endpoint of median overall survival which was 8-8.5 months for both arms. Among a host of pre-specified subgroup analyses, those with a short interval from first- to second-line treatment (<5 months, n=198) achieved a “significant” improvement in survival from 6 to 9 months with the addition of NGR-hTNF.
Bottom Line: There’s some pretty cool science behind conjugating NGR to TNF-α in order to substantially increase the therapeutic window, but it hasn’t panned out yet for mesothelioma. | Gregorc, Lancet Oncol 2018