Editors' ChoiceDrug Discovery

This Changes Everything, Twice!

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Science Translational Medicine  09 Mar 2011:
Vol. 3, Issue 73, pp. 73ec31
DOI: 10.1126/scitranslmed.3002337

Pancreatic neuroendocrine tumors (PNETs), which occur rarely (1.3% of all pancreatic tumors), have been in the news of late thanks to a famous patient: Apple co-founder and CEO Steve Jobs is currently on medical leave for issues related to this cancer. Although HIPAA regulations and the fear of collapse in Apple share price have prevented any leak of Jobs’ clinical status, two recent studies published in the New England Journal of Medicine should give optimism to Jobs, Apple shareholders, and, most importantly, all PNET patients.

Two groups report positive results in phase III clinical trials of orally available small molecules for PNETs. The current standard of care is chiefly surgical, and patient prognoses are often poor if the tumor is inoperable. The two new studies each build on strong preclinical data and confirmatory phase I and II studies. Yao et al. studied the mammalian target of rapamycin (mTOR) inhibitor everolimus, which blocks growth of PNET cells through inhibition of the mTOR signaling pathway. Raymond et al. tested the tyrosine kinase inhibitor sunitinib, which inhibits signaling with vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in PNETs.

Both studies were conducted in patients bearing advanced, progressive malignant PNETs and were well-powered, randomized, double-blinded studies (410 patients in the everolimus study and 171 patients in the sunitinib study). Everolimus treatment resulted in a 65% reduction in the risk of progression. (Compare the median progression-free survival of 11.0 to 4.6 months in the placebo controls.) Treatment with sunitinib similarly doubled median progression-free survival (11.4 versus 5.5 months). Future follow-up studies will determine the net increase in life span afforded by these treatments. In the meantime, these important results offer new hope to patients with PNETs—which are often refractory to current treatments—and are likely to change the standard of care.

J. C. Yao et al., Everolimus for advanced pancreatic neuroendocrine tumors. N. Engl. J. Med. 364, 514–523 (2011). [Abstract]

E. Raymond et al., Sunitinib malate for the treatment of pancreatic neuroendocrine tumors, N. Engl. J. Med. 364, 501–513 (2011). [Abstract]

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