Editors' ChoiceCancer

Precision cancer medicine: Hype or hope?

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Science Translational Medicine  23 Sep 2015:
Vol. 7, Issue 306, pp. 306ec164
DOI: 10.1126/scitranslmed.aad3623

Traditional cancer treatments rely on the use of cytotoxic agents, and the choice of regimen is based on the cancer’s anatomical origin and histology. Advances in cancer genomics and molecular profiling have shown that different cancers can be driven by the same mutations/signaling pathways, and treatment based on the molecular abnormality rather than anatomical origin can be effective. Such molecularly targeted strategies have been termed precision cancer medicine. For example, some gastric cancers overexpress HER2, a well-established abnormality in breast cancer. For these cancers, the addition of trastuzumab (targeting HER2) has improved clinical outcomes. In addition, it was found that most hairy cell leukemias have BRAF mutations that are commonly present in melanoma and basal cell cancers. In these patients, BRAF inhibitors were found to be highly effective. However, precision cancer medicine isn’t always successful. Despite their success in the cancers mentioned above, BRAF inhibitors are largely ineffective in colorectal cancers harboring the same mutation. Because of such mixed results, clinical trials are needed to examine the effectiveness of precision medicine in cancer.

The SHIVA study is a multicenter, open-label, proof-of-concept, randomized, controlled phase 2 trial comparing precision medicine with standard care in cancer treatment. One hundred and ninety-five patients with actionable abnormalities matching 1 of 10 available treatment regimens were randomized, with 99 in the experimental group and 96 in the control group. With a median follow-up of 11.3 months, the median progression-free survival was 2.3 months (95% CI 1.7 to 3.8) in the experimental group versus 2.0 months (1.8 to 2.1) in the control group. The difference was not statistically significant. The investigators concluded that the use of molecularly targeted agents outside of their indications does not improve progression-free survival.

Although the results of SHIVA do not support precision cancer medicine, there are several caveats. First, the study is a phase 2 study with a relatively small sample size. In addition, the study only included 10 treatments targeting 8 signaling pathways. Therefore, the findings will need to be validated in a larger randomized phase 3 trial. To fill this need, NIH/NCI has initiated the NCI-MATCH trial that will screen 3000 patients and enroll 1000 patients. The NCI-MATCH trial will target “actionable” genetic mutations and plan to evaluate at least 20 targeted therapeutics. Moreover, grouping patients by molecular profile alone may not be personalized enough, and it may be necessary to consider both cancer type and molecular abnormalities to realize the hope of precision medicine.

C. Le Tourneau et al., Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): A multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 10.1016/S1470-2045(15)00188-6 ( 2015). [Abstract]

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