Durvalumab

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Durvalumab
Mass / length primary structure 146,300.0  Da
Identifier
External IDs
Drug information
ATC code L01 XC28
DrugBank DB11714
Drug class Monoclonal Antibodies , Antineoplastic Agents

Durvalumab is a monoclonal antibody (type: IgG1κ, human) that is approved for the treatment of lung cancer . The launch of the drug was classified as a step innovation.

pharmacology

Durvalumab is a checkpoint inhibitor and is used for immunotherapy . The antibody binds specifically to PD-L1 (programmed cell death ligand 1).

PD-L1 interacts with PD-1 (programmed cell death protein 1) and CD80 (lymphocyte activation antigen) and thereby inhibits the activity of T cells ( cytotoxic activity , proliferation , production of cytokines ). This is a mechanism used by tumor cells to protect themselves against the body's own immune system ( immune evasion ). Durvalumab suppresses the interaction between PD-L1 / PD-1 and PD-L1 / CD80 and increases the proliferation and activity of T cells against tumor cells (antitumor response).

The plasma half-life is approximately 18 days.

indication

Durvalumab is approved for the indication of locally advanced, inoperable non-small cell lung cancer ( NSCLC , stage III) in adults. Although the effectiveness is classified as relatively independent of the PD-L1 status, the tumor cells should nevertheless show an expression of the surface protein PD-L1 of ≥ 1% (increased effectiveness).

In addition, approval for the treatment of urothelial carcinoma has been granted in some states .

forecast

Durvalumab is used when cancer has not been found to be progressing after platinum and radiation- based therapy. The substance extends the patient's progression-free survival. The median overall survival with placebo in the relevant studies was 29 months. It could not be determined for durvalumab after> 3 years (as of 2018). The mean progression-free survival was 16.8 months (placebo: 5.6 months).

Side effects

More common side effects are:

Therapy-limiting factors are presumably largely due to the immune-stimulating effect. These can include various inflammatory reactions, for example in the context of pneumonia , hepatitis and colitis . Animal studies suggest possible teratogenic properties.

Early benefit assessment

In Germany, since 2011, newly approved drugs with new active ingredients must be subjected to an " early benefit assessment " by the Federal Joint Committee (G-BA) in accordance with Section 35a SGB ​​V if the pharmaceutical manufacturer wants to achieve a higher sales price than just the fixed amount . Only if there is an additional benefit can the pharmaceutical manufacturer negotiate a price with the umbrella association of statutory health insurance companies. The dossier evaluations, on the basis of which the G-BA makes its decisions, are created by the Institute for Quality and Efficiency in Health Care (IQWiG) .

In 2019, durvalumab was evaluated as monotherapy for the treatment of locally advanced, inoperable non-small cell lung cancer (NSCLC) in adults whose tumors express PD-L1 in ≥ 1% of tumor cells and whose disease has not progressed after platinum-based chemoradiotherapy using this procedure. According to the G-BA decision, there is a hint of a considerable additional benefit compared to Best Supportive Care as an appropriate comparator therapy.

Finished medicinal products

The drug manufacturer AstraZeneca has been providing a concentrate for the preparation of an infusion solution ( intravenous ) with 50 mg / ml durvalumab under the trade name Imfinzi® since October 2018 .

Individual evidence

  1. ↑ Entry on durvalumab in the DrugBank of the University of Alberta , accessed October 29, 2018.
  2. ↑ A18-69 Durvalumab (non-small cell lung carcinoma) - benefit assessment according to § 35a Social Code Book V ; Accessed April 20, 2020.
  3. ↑ A19-21 Durvalumab (non-small cell lung cancer) - addendum to commission A18-69 ; Accessed April 20, 2020.
  4. ↑ Benefit assessment procedure for the active ingredient durvalumab (non-small cell lung cancer, maintenance therapy) ; Accessed April 20, 2020.

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