PD-L1 positive lung adenocarcinoma Copyright © 2018 Michael Bonert 

PD-L1 positive lung adenocarcinoma Copyright © 2018 Michael Bonert

Chemotherapy has been the mainstay treatment for most solid organ malignancies. The introduction of immunotherapy, which works by potentiating patients own immune system to control cancers, has revolutionised cancer management. A Nobel prize was awarded to two main researches, James P Allison and Tasuku Honjo, for discovering cancer therapy by inhibition of negative immune regulation.

Dr Mihitha Ariyapperuma (Ari), Medical Oncologist, Subiaco

Dr Mihitha Ariyapperuma (Ari), Medical Oncologist, Subiaco

Immunotherapy agents have been one of the main treatment modalities in melanomas showing around a 70% response rate with 58% of patients showing more than three years of survival in trials.

Immunotherapy has been used in lung cancer for some years, and, more recently, it has expanded into multiple other types of malignancies. In lung cancer with high PD-L1(programmed death-ligand 1) expression rate, median progression-free survival is around 10 months on immunotherapy alone compared to six months with chemotherapy.

Common instances where immunotherapy is used in cancer treatment include metastatic non-small cell lung cancers.  maintenance treatment of stage III lung cancers following definitive chemo-radiotherapy, adjuvant treatment of high-risk melanomas, metastatic melanomas, clear cell renal cell cancers in first-line and second-line settings and oropharyngeal squamous cell cancers.

Long-term responses are seen in a considerable proportion of patients depending on type of cancer. Trials are under way combining immunotherapy with chemotherapy and there are access programs open in Australia for combined treatments. Examples are combining chemotherapy and immunotherapy in advanced lung cancers and triple negative breast cancers.

The expression of PD-L1 receptor levels in cancer tissue has been a predictor for response to immunotherapy.  Commonly used immunotherapy agents in clinical practice include PD1 (Programmed cell death protein 1) inhibitors, PD-L1 inhibitors and CTLA-4 (Cytotoxic T-lymphocyte associated protein 4) inhibitors. There are multiple other types of immunomodulatory agents at various stages of development.

Immunotherapy is available under PBS for multiple solid organ malignancies including melanoma, lung cancer, renal cell cancer and head and neck squamous cell cancer.

The indications for immunotherapy are expanding. Several access programs are currently active in Australia, providing patients free access in different conditions.

Side effects seen with immunotherapy are quite different to chemotherapy related side effects. These include hepatitis, colitis, pneumonitis and endocrinopathies. Even though immunotherapy seems to be generally better tolerated than chemotherapy, some of these side effects can be life-threatening so early recognition is vital.

Key messages:

  • Immunotherapy is used increasingly in solid organ malignancies
  • Immunotherapy tends to be more tolerable compared to chemotherapy
  • Combining chemotherapy with immunotherapy is a trend showing promising results but increasing the probability of side effects.

Immunotherapy agents – a key to acronyms:

  • PD-1 (Programmed cell death protein 1)
  • PD-L1/L2 (programmed death-ligand 1 and 2)
    CTLA-4 (cytotoxic T-lymphocyte-associated protein 4)
  • TIGIT (T-cell immunoreceptor with Ig and ITIM domains)
  • BTLA (B- and T-lymphocyte attenuator)
  • VISTA (V-domain Ig suppressor of T-cell activation)
  • TIM-3 (T-cell immunoglobulin and mucin domain 3)
  • GITR-Glucocorticoid-induced tumour necrosis factor (TNF)-like receptor

Immunotherapy agents currently in common use in Australia for treatment of solid organ malignancies:

  • Nivolumab: melanoma, non-small cell lung cancers, head and neck cancers , clear cell renal cell cancers
  • Pembrolizumab: melanoma, non-small cell lung cancers, urothelial cancers
  • Durvalumab: non-small cell lung cancers
  • Atezolizumab: non-small cell lung cancers

Image credit: PD-L1 positive lung adenocarcinoma Copyright © 2018 Michael Bonert  – Image cropped – CC BY-SA 4.0

References available on request.

Questions? Contact the editor.

Author competing interests: nil relevant disclosures.

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