Cell: Clinical trials on trial
As Hiroyuki Mano entered the oncology ward at Seoul National University Hospital, he was amazed to see his patient walking around, asking people to recommend the best local restaurant. Just days before, the patient had been hooked up to oxygen monitors. Cancer had spread rapidly through his lung, making it difficult to breathe and swallow. He had been air-lifted from Japan to Korea to get access to a clinical trial that was testing a new drug, crizotinib.
The crizotinib trial was unusual because it did not contain a control arm for placebo treatment. In 2008, Mano and his colleagues at Jichi Medical University identified a fusion protein of anaplastic lymphoma kinase (ALK) with another protein EML4, resulting from a chromosomal rearrangement seen in about 4% of lung cancer patients. The ALK-EML4 fusion is a powerful driver of cancer but is potently inhibited by crizotinib.
In this trial, doctors only enrolled patients testing positive for the ALK biomarker. Crizotinib treatment resulted in dramatic shrinkage of the tumors, visibly and almost immediately, in some cases within 48 hr. There could be no doubt that the drug was working. Even though only 82 patients were enrolled, the results were clearly statistically significant. Dr Mano’s patient was on his feet in days.