This story begins when my son was diagnosed with cancer at the age of eight. Like most patients who are lucky to be in an international city, he received nine consecutive lines of treatment, one after another, prescribed in the exact order of “cancer textbooks”: from nasty chemotherapy to sophisticated targeted drugs.
Were these drugs the right match for the tumour of my child? No, they were just thrown at him in a blind manner, hoping for the best.
The worst happened – my son Gaspard died.
I kept asking myself how cancer could remain a fatality in an era when the human genome – our genetic code – has been deciphered and can be manipulated to cure rare diseases; when AIDS is under control; when cars do not need drivers; and man is conquering space?
Here started my personal war against cancer. I had no strategy, no troops, no weapons to face the enemy, only my grief and determination to make things change.
Yet I knew change was needed. Treatment options have not really varied for years; research silos remain unbreakable; the costs of treatment are exorbitant; and advances in genomic-based treatment of cancer are unacceptably slow.
And so it came to pass that a year after my son’s death, in October 2010, a small group of prominent oncologists established a global collaboration of cancer centres, drug makers, technology and insurance companies built on refusal of the status quo. The network was ambitiously named the Worldwide Innovative Networking (WIN) Consortium in personalised cancer medicine, and I soon joined as director of operations.
The good news when it comes to cancer is that some important breakthroughs have been achieved recently with the introduction of targeted and immune drugs. Indeed, evidence is building in clinical trials, research and case reports to suggest that patient outcomes are improved when a specific targeted medicine can be matched to an identified anomaly of the tumour’s DNA (a “genomic aberration”).
However, the bad news is that in the majority of cases, this does not work or it works only briefly. Not all advanced solid tumours harbour potentially “actionable” genomic anomalies that can be treated with a targeted therapy. So far the approach has benefited only a small portion of patients, for a variety of confounding factors. We lack tools to understand which DNA anomaly is important versus not important, we have difficulties to predict whether a drug that targets an identified anomaly will be effective in terms of patient’s outcome. In other words we still do not know how to match a patient’s cancer to the right drug.
Even those cancer patients who are “lucky enough” to have a tumour harbouring an anomaly that can be treated with a targeted therapy, are almost guaranteed to relapse once the disease develops resistance.
In the meantime the statistics are staggering. 14 million new cancer cases are registered every year. By 2030, the global burden is expected to grow to 21.7 million new cancer cases. This means that cancer will affect everyone in the world, sooner or later, directly or indirectly. The ‘emperor of all maladies’ already claims 8.8 million deaths per year, making cancer a leading cause of death worldwide, with lung cancer being the top killer.
Lung cancer develops silently and when the first clinical symptoms appear, it is often too late – the patient is already in an advanced stage of the disease that is then incurable.
Over the past 50 years lung cancer treatment has been largely ineffective. As Dr. Razelle Kurzrock, senior deputy director for clinical science at UCSD’s Moores Cancer Center and Head of WIN Clinical Trials Committee, said in a recent interview: “we were blindly throwing drugs at [patients] hoping something will stick”.
Around 14 per cent of non-small cell lung cancer (NSCLC) patients with stage IIIA disease survive five years after diagnosis; with stage IIIB disease the five-year survival rate is only 5 per cent. When the disease has spread to other parts of the body, the five-year survival rate drops to 1 per cent. Unfortunately 60% of patients are diagnosed at late stage IV.
With the current path of drug and biomarker development, it will take decades to achieve significant improvement in cancer outcomes. Personalised oncology, aimed at giving the right treatment to each patient, is therefore a long and winding road that has left many patients on the side.
Cancer is complex and pernicious, yet it does not develop in vacuum, but rather in an individual. Precisely because cancer is so complex, giving patients one targeted therapy does not make much biological sense. It may produce response in some patients, but responders will inevitably develop resistance and succumb to the disease. It is time to look at patients as individuals and to develop combination treatments, or ‘cocktails’. But how can we determine personalised therapy combinations that can be used to treat lung cancer, or other deadly malignancies? There is no clear answer yet.
The easiest way to cure cancer is to prevent it. Global tobacco control is critical to achieve this goal. When lung cancer is detected at an early stage, surgery and adjuvant therapies are enough to achieve cure. But what if the patient arrives too late, having an advanced form of the disease? How can we deliver the gift of time and quality of life that my son was denied? The strategy here resides in switching from the current monotherapy rule given in consecutive lines, towards the rational combination(s) of targeted drugs. But how many drugs do we need to combine together?