Introduction

Rucaparib (trade name: Rubraca) has been approved in Germany since May 2018 for the treatment of high-grade epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer in women if the cancer has progressed or returned despite them having previous platinum-based chemotherapy. In this situation, the drug may only be given to women who have a mutated BRCA gene. In January 2019, the approval status was expanded to include treatment for women without the BRCA mutation who have had treatment before and whose tumor has responded to platinum-based chemotherapy. Rucaparib has only been approved for patients who have had effective treatment with platinum-based chemotherapy.

In about 90 out of 100 women with ovarian cancer, the cancer develops in the epithelial layer covering the ovary. This type of ovarian cancer is known as epithelial ovarian cancer. If the cancer progresses, it can spread to the abdominal cavity and form metastases on the peritoneum (the lining of the abdominal cavity).

The causes of ovarian cancer are not fully understood. There are often several mutations in the DNA of the cells. They commonly affect the genes BRCA1 or BRCA2, which also play a role in breast cancer. The abbreviation BRCA stands for breast cancer gene.

Ovarian cancer often stays undetected for a long time because there are usually no symptoms, or only nonspecific symptoms. When the tumor is detected, it’s often already at an advanced stage. Advanced ovarian cancer is removed surgically and treated with chemotherapy. If it returns despite treatment, complete recovery is often no longer possible. Treatment then aims to stop the cancer from getting worse for as long as possible and reduce the symptoms. Rucaparib is used in that situation to inhibit several proteins that affect tumor growth.

Application

Rucaparib is available in tablet form, in three different strengths: 200, 250 and 300 mg. The recommended dose is 600 mg of rucaparib twice a day. The dose can be adjusted depending on any side effects that occur and the results of blood tests. The treatment is stopped if severe side effects arise or if the cancer progresses.

Other treatments

Treatment with topotecan or doxorubicin is an option for women with a BRCA mutation whose cancer has progressed or returned despite previous treatments and who would not like to have another platinum-based chemotherapy.

Watchful waiting is an option for women with advanced ovarian cancer who have had effective platinum-based chemotherapy. That means that the patient will continue to be cared for and newly occurring symptoms will be investigated. Any treatment decisions are made together with the patient.

Assessment

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of rucaparib compared with the standard treatments for women with advanced epithelial ovarian cancer.

The manufacturer didn’t provide any suitable data regarding advantages or disadvantages of rucaparib in comparison with topotecan or doxorubicin. The manufacturer provided only one suitable study which involved women who had effective platinum-based chemotherapy and who were able to opt for watchful waiting. The study that was provided involved a total of 564 women. 375 of them received rucaparib while the other 189 were given a placebo (fake medication). All of the women had regular examinations and were in good general health despite the advanced stage of their condition.

What are the advantages of rucaparib?

Rucaparib wasn’t found to have any advantages compared to the placebo.

What are the disadvantages of rucaparib?

  • Symptoms of the disease: In terms of symptoms like pain, abdominal cramps or exhaustion, early data analyses suggest that rucaparib has a disadvantage compared with the placebo.
  • Severe side effects: Here too, the study suggests that it has a disadvantage: Side effects, such as serious disorders of the blood and lymphatic system, were more common and developed sooner when women used rucaparib. About 60 out of 100 women who took rucaparib had severe side effects, compared to only 16 out of 100 women who took the placebo.
  • Treatment stopped due to side effects: The study suggests that rucaparib has a disadvantage here, too. About 16 out of 100 women in the rucaparib group stopped the treatment due to side effects, compared to only 2 out of 100 women in the placebo group.
  • Early analyses also suggest that rucaparib has a disadvantage compared with the placebo regarding the following side effects:
    • Illnesses and problems affecting the membranes lining the mouth
    • Gastrointestinal (stomach and bowel) problems
    • Sensitivity to light
    • Loss of taste / Changes in taste

No difference

No difference was found in terms of disorders of the bone marrow and leukemia. There was no relevant difference related to overall health or disorders of the skeletal muscles, the connective tissue and the bones.

What remains unanswered?

  • Life expectancy: Based on the available data, it isn't possible to tell whether rucaparib has any advantages or disadvantages compared with watchful waiting.
  • Health-related quality of life: The manufacturer didn’t provide any data on this.

More information

This information summarizes the main results of reviews produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The reviews were commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the reviews and the hearings received, the G-BA passed a resolution on the added benefit of rucaparib (Rubraca) for women who have a BRCA mutation and who have had treatment at least twice before or who are having maintenance treatment.