Pemetrexed (Alimta; Eli Lilly), a next-in-class antifolate drug, was first approved by the US Food and Drug Administration (FDA) in 2004 in combination with cisplatin for the treatment of pleural mesothelioma. This marketing authorization entailed a relatively small patient population, and through 2007, the drug’s sales never eclipsed $1 billion in a calendar year; 2008 marked the drug’s second approval, this time for the treatment of nonsquamous non–small cell lung cancer (NSCLC). With this approval and perceived superiority in this histology, the use of pemetrexed skyrocketed, displacing older, cheaper cytotoxic drugs and earning Eli Lilly at least $1 billion annually for this medication.1 The approval of pemetrexed for lung cancer has been credited for the transformation of a rarely used cytotoxic drug to cancer therapy blockbuster,1 and data suggest pemetrexed was preferentially used over alternatives between 2007 and 2011.2 The Figure depicts rising sales of the drug over time. These stellar sales of pemetrexed may be credited, at least in part, to 2 subgroup analyses that showed improved overall survival (OS) in nonsquamous histology NSCLC but not squamous histology.3 However, several unusual observations about these findings raise the provocative question: Is the benefit in the nonsquamous histology real or spurious? If spurious, the use of pemetrexed may be one of the most common and costly medical practices driven by a subgroup finding in all of medicine.
Gyawali B, Prasad V. Pemetrexed in Nonsquamous Non–Small Cell Lung Cancer: The Billion Dollar Subgroup Analysis. JAMA Oncol. 2018;4(1):17–18. doi:10.1001/jamaoncol.2017.1944
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