ASCO 2017 Annual Report again picks immunotherapy as “Advance of the Year “

ASCO, the American Society of Clinical Oncology, is probably best known to followers of the pharma and biotech industries for its high profile annual conference, always the subject of intense sector analyst scrutiny.  ASCO also publishes a highly-readable annual report highlighting clinical advances in cancer therapy and the shape of future research.

Once again, immunotherapy (dubbed “Immunotherapy 2.0” by ASCO) takes the honours as “Advance of the Year”, underscoring the breakthrough nature of this approach to cancer treatment and its expanding role across a growing number of cancer indications.

Put very simply, immunotherapy utilises the patient’s own immune system to combat cancer. Tumours thrive by deploying a variety of countermeasures which are highly effective in subverting the immune response.  A mechanism common to several tumour types is surface expression of proteins that lock onto receptors (“immune checkpoints”) present on T cells,  resulting in their deactivation. By deliberately blocking this interaction, T-cell “seek and destroy” functions can be restored.

Immune checkpoint inhibitors were first approved on the basis of their efficacy in metastatic melanoma, with the first being Yervoy® (ipilimumab: Bristol Myers Squibb) in 2011, followed by Keytruda® (pembrolizumab: Merck) and Opdivo® (nivolumab: Bristol Myers Squibb) in 2014 and,  most recently, Tecentriq® (atezolizumab: Roche) for the treatment of some forms of lung cancer. A number of other biologic immune checkpoint inhibitors are in late stage clinical evaluation.

From the outset, checkpoint inhibitor treatment has been notable for impressive increases in patient survival, although not across the board. Reliable identification of those patients most likely to benefit from checkpoint inhibitor therapy remains a frustration. Optimum duration of therapy also remains to be established. Given the cost of checkpoint inhibitor treatment (around £30,000 before an undisclosed discount in the UK and around $150,000 in the US), patient selection and length of treatment are of key importance to healthcare systems already struggling with soaring cancer therapy expenditure.

Recent checkpoint inhibitor approvals include treatment of head and neck, bladder and renal cancers and Hodgkin’s lymphoma, and evaluation is progressing in liver, breast, gastric and other cancers. The need to attain market dominance is a major driver of clinical trial activity: at the end of 2016, Merck’s Keytruda® was being trialled against 30 tumour type in more than 350 registered studies, of which around 100 studies will evaluate treatment combinations.

Hundreds of micro and mid-cap companies are looking to stake a claim in the immunotherapy (aka “immuno-oncology) space. Some are hopeful that repurposed drugs can modify the tumour microenvironment to favour the immune system, while others believe that combination with checkpoint inhibitors and other agents can boost the so far disappointing efficacy of cancer vaccines.

Tumour immunology remains poorly understood. Potential big winners in next generation immunotherapy are those companies engaged in the unravelling of tumour defence mechanisms to find exploitable vulnerabilities.

Who knows, but given the rate of progress, the 2027 ASCO “Advance of the Year” could well be “Immunotherapy 12.0”.

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ASCO 12^th Annual Report on Progress Against Cancer. 2017 Clinical Advances. Online 1^st February 2017    http://tinyurl.com/zwzv5vg