RSS feedThe completion of the first survey of the entire human genome was announced with much excitement to the world by President Clinton on 25th June 2000. Subsequent to that many researchers and clinician scientists spoke enthusiastically about the day when we will be able to tailor medical treatment specifically to each individual. This will lead to reduced side-effects, better efficacy and success in treating or even curing their condition. If this indeed becomes a reality, personalized medicine would arguably be most welcome in the field of medical oncology. This is because chemotherapy is associated with side-effects, some of which can be life-threatening. Personalized medicine will also take away the ‘trial & error’ evil of trying various drug combinations in order to arrive at one which suits your tumour best.
Molecular targeted therapy with agents such as bevacizumab (Avastin), cetuximab (Erbitux) and panitumumab (Vectibix) have made an impact in the field of medical oncology. However, they are expensive agents and clearly not all patients would benefit from their use. The approach so far has been ‘try it and see if there is a response’. Two recent scientific studies may help to put some science into this empirical approach to the treatment of colorectal cancer.
The first study from Australia studied the K-ras gene within the colorectal tumour of 394 patients with advanced cancer. These patients were randomly assigned to best supportive care alone or cetuximab [an anti-epidermal growth factor receptor (EGFR) antibody] plus best supportive care (NEJM 2008; 359: 1757 – 1765). The researchers assessed whether the presence or absence of the K-ras gene mutation was associated with survival in the cetuximab + supportive care group. The study found that K-ras gene mutation adversely affected survival. In patients with wild-type (meaning non-mutated) K-ras tumours, cetuximab treatment was associated with significantly improved overall survival (median survival 9.5 vs 4.8 months in supportive care alone) and progression-free survival (median 3.7 vs 1.9 months). In patients with K-ras gene mutation tumours, the overall survival and progression-free survival between those treated with or without cetuximab was no different.
At the recent second Annual Molecular Markers in Cancer Meeting held in Hollywood, Florida, researchers presented their pooled analysis of 4 large trials of patients with metastatic colorectal cancer treated with panitumumab. Panitumumab, an anti-EGFR antibody, has been approved as monotherapy for patients with metastatic colorectal cancer who have failed previous chemotherapeutic regimens in USA and for patients with wild-type K-ras tumours in the European Union. A total of 715 cases were studied, 395 cases of wild-type K-ras tumour and 320 cases of K-ras mutated tumour. None of the patients with K-ras mutated tumour responded to panitumumab. Of those with wild-type K-ras tumour, only 13.7% showed an overall response to panitumumab. The overall survival was 37% longer in those with wild-type K-ras tumours (8.3 months) than in those with K-ras mutated tumours (5.7 months). The progression-free survival for patients with wild-type K-ras tumours was nearly twice as long (3.3 vs 1.7 months).
These studies have shown us that we have taken the first step of what looks like a long journey towards truly personalized medicine. However, we must not lose hope and must pray that we will come up with better agents that target the tumour more effectively in the future.
(In the mean time, you can get your K-ras tumour status checked for free if you are receiving treatment in Singapore, courtesy of Merck, the manufacturer for Erbitux.)
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