Clinical trial of advanced metastatic colorectal cancer brings ‘surprisingly good results,’ say experts

Colorectal cancer is one of the most common cancers and its incidence continues to grow. According to the International Agency for Research on Cancer (IARC), in 2020 this cancer was diagnosed in 2 million people, and in 2040 the number of detected cases of this disease will exceed 3 million. Every year, 1 million patients die, and in 2040 there may even be 1.6 million deaths.

The good news is that the survival rate of this cancer is significantly increasing thanks to the progress in therapy. According to data presented at the recent World Congress on GI Cancer in Barcelona, it has more than quadrupled over the last two decades. While only 18 percent of patients survived five years in 2004-2006, in the period 2013-2015 it was 89 percent.

Patients with advanced metastatic colorectal cancer who have already been treated are a challenge for oncologists. Five-year survival is achieved in only 11 percent of patients. There is hope, however, that this group will increase thanks to the use of a new therapy involving the combination of two drugs, ones that have been used for a long time. An international clinical trial has shown that it significantly extends the life of the most severely ill patients.

'This study generated a lot of interest. For the first time, it was possible to obtain a new treatment so quickly, from the idea to its soon-to-be registration. The idea was to test the concept of therapy proposed by a group of specialists from Denmark, and - as it turned out - their initial results were confirmed on a large cohort of patients,’ says Professor Lucjan Wyrwicz, head of the Oncology and Radiotherapy Clinic of the National Institute of Oncology in Warsaw.

The study, called Sunlight, was presented at the American Society of Clinical Oncology (ASCO) congress in Chicago at the end of May. A few days ago the updated results were presented in Barcelona at the European Society of Clinical Oncology (ESMO) World Congress on GI Cancer. It was also published by the News England of Medicine.

Professor Wyrwicz explains that the new treatment for advanced metastatic colorectal cancer consists in combining two drugs, a chemotherapeutic drug called trifluridine/tipiracil with a monoclonal antibody - a biological preparation known as bevacizumab. Patent rights for bevacizumab have expired and its equivalents (so-called biosimilars) are available on the market.

'You could call it a recycling of a well-known drug. But it turned out that these two drugs in combination in the third-line treatment of recurrent advanced colorectal cancer are almost twice as effective compared to monotherapy with trifluridine/tipiracil - also in patients who have previously been treated with bevacizumab,’ Wyrwicz says.

According to a clinical trial conducted in 96 centres in 18 countries including Poland, the combination of these two drugs used in the third line of treatment extended the survival time of patients by 10.8 months, while the use of one drug (trifluridine/tipiracil) - by 7.5 months. Patients survived without progression for 5.6 months and 2.4 months, respectively.

'We expected them to be positive, but the Sunlight study showed that they were much better than we expected,’ says oncologist Professor Gerald Prager from the Medical University of Vienna.

According to Professor Wyrwicz, patients not only live longer after treatment with trifluridine/tipiracil combined with the monoclonal antibody bevacizumab, but also show a longer period of disease control and therefore do not experience greater toxicity. ‘Adverse events in both groups were the same, despite the fact that with almost twice as long survival, the risk is usually greater,’ he adds.

The reasons for this phenomenon - the lack of additional toxicity - may vary. 'When a drug is used for a longer period, doctors know better how to handle its side effects and are less concerned about using it. Doctors simply know how to handle patient selection and potential side effects. An important element here, however, is the selection of the patient for therapy, and the main criterion is the patient's performance expressed on the medical scale (ECOG),’ Wyrwicz says. 

He adds: ‘This is very important, because patients with a worse performance status feel more negative effects of treatment. And trifluridine/tipiracil is a drug that has side effects after a longer period of use, at the same dose of treatment, because the body metabolises the drug less efficiently over time. As a result, in a patient with an average performance status, the toxicity of the therapy can accumulate, which we do not see in patients with a better performance status.’

Wyrwicz explains that there is no instrumental way to measure the patient's performance. It is crucial to collect a medical history and talk frequently with the patient's family, because the patients often avoid talking about all their symptoms during appointments.

Professor Gerald Prager - like other experts - is convinced that the new combination therapy will soon become the standard of care in the third line of treatment for patients with colorectal cancer. Extremely quickly, on June 22, 2023, after the recent publication of clinical trials, the European Medicines Agency (EMA) approved the new treatment for use in the European Union. (PAP)

PAP - Science in Poland, Zbigniew Wojtasiński

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