Introduction

The drug atezolizumab (trade name: Tecentriq) has been approved in Germany since September 2017 for the treatment of advanced urothelial carcinoma.

The word “urothelial” comes from the medical term for the type of membrane tissue lining the urinary tract (urothelium). The urinary tract includes the renal pelvis, the ureter, the urinary bladder and the upper part of the urethra. In more than 90 out of 100 people with urothelial carcinoma, it develops in the bladder (bladder cancer).

The early symptoms usually include painless bleeding in the bladder, turning the urine a brownish color. People may also feel like they have to urinate more often. The symptoms of advanced urothelial carcinoma may include pain in the abdomen or kidneys, enlarged lymph nodes, or bone pain. It is more common in men than in women.

Atezolizumab is used to treat advanced bladder cancer or other urothelial carcinomas that can no longer be surgically removed or that have spread to other parts of the body (metastasis). Atezolizumab blocks the effect of the PD-L1 protein produced by the tumor tissue. This protein weakens the body's immune response, particularly the activity of T cells, against the tumor cells. The new drug is meant to stimulate the immune response to the cancer cells in order to inhibit tumor growth.

Application

Atezolizumab is given every three weeks as an infusion (an IV drip) into a vein at a dose of 1,200 mg. Treatment is stopped if the disease gets worse despite treatment or if very severe side effects arise.

Other treatments

For patients with bladder cancer or another urothelial carcinoma who can't have cisplatin-based first-line treatment and whose tumor has large amounts of the protein PD-L1 in it, the standard treatment is chemotherapy that has been individually tailored by a doctor.

For patients whose cancer returns within 6 months after treatment with platinum-based chemotherapy (early relapse), the drug vinflunine is an option. If the cancer comes back more than 6 months after chemotherapy (late relapse), another course of cisplatin-based chemotherapy can be considered.

Assessment

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) again looked into whether atezolizumab has any advantages or disadvantages for people with advanced bladder cancer (urothelial carcinoma) when compared with the current standard treatments.

In 2019, the manufacturer didn't provide relevant data concerning first-line treatment.

In the study provided by the manufacturer for the first assessment in 2017, only the data of patients who had already had platinum-based chemotherapy were suitable for the analysis. Treatment with atezolizumab was compared with a standard treatment with the drug vinflunine: 252 people had treatment with atezolizumab, and 250 had treatment with vinflunine. Despite the advanced stage of the disease, all patients were in good general health. The following results were found for them:

What are the advantages of atezolizumab?

  • Nausea and vomiting: In terms of these symptoms, the study suggests that atezolizumab has an advantage in people with a low count of PD-L1-positive immune cells. It took longer for nausea or vomiting to occur or worsen in people who had treatment with atezolizumab: While it took about 6 months for this to happen in half of the people in the atezolizumab group, it only took about 2 months for it to happen in half of those in the standard treatment group. There was no difference between the treatments in people with a high count of PD-L1-positive immune cells.
  • Insomnia: Here, too, the study suggests that atezolizumab has an advantage for people with a low count of PD-L1-positive immune cells. It took longer for insomnia to occur or worsen in people who had treatment with atezolizumab: It took about 4 months for this to happen in half of the people in the atezolizumab group, and only about 2 months for it to happen in half of those in the standard treatment group. For those people with a high count of PD-L1-positive immune cells there was no difference between the treatments.
  • Health-related quality of life: The study suggests that, compared to those who had the standard treatment, it took longer for men who had treatment with atezolizumab to start feeling limited regarding their family life, doing things with friends, and other social activities. There was no difference here in women. The two treatments were not found to differ in terms of their effects on other aspects of health-related quality of life, such as everyday physical activities, concentration, memory or feeling down.
  • Serious side effects: The study also suggests that atezolizumab has an advantage over with the standard treatment in terms of serious side effects such as severe constipation or severe febrile neutropenia. Febrile neutropenia is the development of fever in a patient who doesn’t have enough immune cells.
  • Treatment stopped due to side effects: There was weak evidence of an advantage here, too: About 9 out of 100 people in the atezolizumab group stopped the treatment due to side effects, compared to nearly 16 out of 100 in the standard treatment group.
  • Inflammations of the mucous membranes: In terms of this treatment-related side effect, the study suggests that atezolizumab has an advantage over the standard treatment.

What are the disadvantages of atezolizumab?

  • Immune-mediated severe side effects: Immune-mediated side effects are medical conditions in which a person's immune system attacks their own body. The study suggests that atezolizumab has a disadvantage here: Almost 6 out of 100 people in this group had immune-mediated side effects, compared to less than 1 out of 100 people who had the standard treatment.
  • Pneumonia and other problems affecting the airways and chest: The study suggests that atezolizumab has a disadvantage in terms of these severe side effects, too. For instance, problems affecting the airways and chest occurred in 4 out of 100 people in the atezolizumab group, while nobody in the group with the standard treatment experienced these side effects.

No difference

  • Life expectancy: No difference was found here. In both groups, half of the participants had passed away within about 8 to 9 months.
  • Health-related quality of life: No difference was found between the treatments in terms of the following symptoms, either:
    • Exhaustion
    • Pain
    • Breathing problems
    • Loss of appetite
    • Diarrhea

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 atezolizumab (Tecentriq): 2017 and 2019.