Precision cancer medicine and therapeutic effect
The term 'precision medicine' is frequently used in a narrow sense in connection with cancer – the idea of providing a drug targeted to an identified tumour mutation, but off-label, to patients with advanced disease after all other systemic tumour-directed treatment has failed. Precision cancer medicine in this sense was launched at the ASCO conference (the world's largest clinical oncology conference) in the spring of 2011 when The University of Texas MD Anderson Cancer Center presented its ongoing long-standing programme in the field of biomarker-driven experimental cancer therapy, published the following year (6).
During the subsequent decade, many extensive initiatives of the same type and generally based on NGS diagnostics were undertaken at large oncology institutions in a number of countries (7–16). When correctly interpreted, the outcome data are disappointing.
The correct outcome measure, the objective response rate, must have the number of patients who undergo NGS analysis as the denominator and the number of patients who achieve an objective therapeutic effect (partial or complete response, determined radiologically) as the numerator. However, reports from clinical trials more or less intentionally emphasise the number of patients who end up starting treatment, not all those who are tested, as the denominator (which is therefore artificially low). Moreover, the number of patients who have radiologically defined stable disease, in addition to those with an objective response, is reported in the numerator (which is thus artificially high). The outcome data are thereby inflated.
As oncologists we have a duty to provide dispassionate information on the possible benefits of precision cancer medicine to our patients with advanced cancer, as well as in the health policy discourse
In simple terms, stable disease in cases of metastatic cancer means that the patient's burden of disease over a predefined treatment period increases by less than 20 % or is reduced by less than 30 %, which are rather arbitrarily chosen radiological target figures. The definition 'stable disease' in itself gives no indication of the extent of the metastatic burden of disease, which is often substantial in end-stage cancer.
A telling example of why stable disease cannot be deemed a treatment response can be seen in patients with widespread liver metastasis which results in hepatic capsule stretch. When the therapeutic outcome in such a patient is scored as stable disease, the patient has thus experienced no change in pain level from the hepatic capsule stretch, as well as adverse effects from the treatment, in the final stage of life – therefore no therapeutic benefit! This poses the rhetorical question: Is it right to report such an outcome as a success for experimental precision cancer medicine? For information, we generally give these patients a daily dose of prednisolone, a simple and inexpensive treatment of the symptoms in question.