Introduction

The fixed-dose combination of trifluridine / tipiracil (trade name: Lonsurf) has been approved in Germany since September 2019 for the treatment of advanced gastric (stomach) cancer. It is a treatment option for adults with stomach cancer that progresses despite previous treatments.

Stomach cancer is caused by the malignant growth of glandular cells in the mucous membranes lining the stomach. The passage between the food pipe and stomach can be affected as well.

Stomach cancer is most common in people over the age of 60. At first it causes general symptoms like stomach ache, nausea and loss of appetite or weight. So it can go unnoticed for a while, or be mistaken for other stomach conditions. Another possible symptom is dark or black stool (poo) – also called tarry stool – caused by bleeding in the stomach.

The cancer tumor is surgically removed, if possible. But sometimes it has already become too large or the cancer has spread to other parts of the body (metastasis) through the blood or lymphatic system. It is then called advanced gastric (stomach) cancer.

The combination of the drugs trifluridine and tiparicil is believed to slow down the growth of the tumor cells.

Application

The fixed-dose combination trifluridine / tipiracil is available in the form of tablets in two different doses: 15 mg of trifluridine / 6 mg of tipiracil, and 20 mg of trifluridine / 8 mg of tipiracil. The dose is determined by the doctor, based on the patient's body surface area and the side effects.

The drug is used in treatment cycles of 28 days each: During the first five days, it is taken twice per day. This is followed by a two-day break from use of the drug, which is then taken again for five days. After a total of 28 days the next treatment cycle begins.

Treatment is stopped if the cancer progresses despite treatment or if the side effects are too severe.

Other treatments

“Best supportive care” (BSC) is the standard treatment for advanced stomach cancer in patients who have had at least 2 previous treatments that didn’t work or weren’t suitable. BSC should be tailored to the patient's individual needs, relieve symptoms such as pain, and improve quality of life.

Assessment

In 2019 the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) wanted to find out whether the fixed-dose combination of trifluridine and tipiracil has any advantages or disadvantages for adults with advanced stomach cancer compared to treatment with BSC.

The manufacturer provided one study involving 507 people. All of the participants had supportive care. 337 of them also received the fixed-dose combination of trifluridine and tipiracil, and the other 170 people were given a placebo instead. All of the patients were in good general health at the start of the study. This is what was found:

What are the advantages of the fixed-dose combination trifluridine / tipiracil?

Life expectancy: The results suggest that the combination drug has an advantage here. The people who received trifluridine / tipiracil passed away after about 6 months on average (median value), compared to about 4 months in the placebo group.

Treatment stopped due to side effects: The study suggests that the combination trifluridine / tipiracil has an advantage here too.

Severe gastrointestinal (stomach and bowel) diseases and problems that occurred just after the medication was taken: The study suggests that trifluridine / tipiracil has an advantage in terms of these severe side effects, too. The problems that occurred after taking the medication included exhaustion, weakness and edemas (swelling caused by fluid retention).

What are the disadvantages of trifluridine / tipiracil?

The study suggests that this combination of drugs also has a disadvantage compared with a placebo concerning the following side effects:

  • Severe anemia
  • Severe neutropenia and severe leukopenia (not enough immune system cells in the blood)
  • Skin conditions

What remains unanswered?

Cancer-related symptoms and quality of life: The manufacturer didn’t provide any suitable data on this.

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the review and the hearings received, the G-BA passed a resolution on the added benefit of the fixed-dose combination trifluridine / tipiracil (Lonsurf).