The study was done among melanoma patients in whom the cancer cells had already spread to the local lymph gland. There is then a great chance of a recurrence of the disease. Half of the patients received, as adjuvant treatment, pembrolizumab and the other half a placebo after surgical removal of the tumour. An adjuvant treatment is intended to reduce the risk of recurrence of the cancer after surgery.
After one year, in 75 percent of patients who received pembrolizumab, the cancer had not yet returned. This was the case with 61 percent of the placebo group. The risk of recurrence of the cancer was, therefore, 43 percent smaller in the pembrolizumab group than in the placebo group.
Surgeon-oncologist Alexander van Akkooi, Dutch coordinator of the study, and internist-oncologist Christian Blank conducted the study in the Netherlands Cancer Institute in Amsterdam. They are happy with the results. Van Akkooi: 'This is the second study that shows the added value of a form of immunotherapy in a relatively early stage of melanoma. With this, we hope that, ultimately, fewer patients will get a further metastatic melanoma and thus have a greater chance of long-term survival.'
Pembrolizumab (brand name Keytruda) is a so-called checkpoint inhibitor, a form of immunotherapy that aims to prevent the cancer cells from sabotaging the effect of immune cells (the T-cells). The medicine has not yet been approved as an adjuvant treatment in the Netherlands, 'but we expect that to happen this year', says van Akkooi. The drug has already been approved in the European Union and in the USA as a remedy against metastatic or inoperable melanoma and other cancers.
Immunotherapy is, as yet, a standard treatment for only a few forms of cancer. In melanoma, cancer of the pigment cells and the most aggressive form of skin cancer, immunotherapy has already shown very good results and has thus been extremely important to - some of - the melanoma patients. However, it is mainly used in an advanced stage of melanoma, when the cancer has already spread throughout the body.
This new study is also the third major study showing that some form of adjuvant therapy in high-risk patients with melanoma works well. "That makes the results very powerful," says Blank. 'Previously, research showed that a high dose of ipilimumab and nivolumab (also forms of immunotherapy) had a beneficial effect. But dabrafenib and trametinib (targeted treatments against the cancer cell itself) have also shown a favourable effect as an adjuvant treatment. '
This double-blind randomized Phase 3 study was coordinated by the European Organization for Research and Treatment of Cancer (EORTC) in collaboration with pharmaceutical company, Merck. More than 1000 patients from 23 countries took part. The Netherlands had an important share in the study and stood in the top five, with 100 patients, of whom 50 were from the Netherlands Cancer Institute.
The research is still ongoing, to be able to measure effects in the long term. But now that immunotherapy as an adjuvant therapy appears to work well, the question arises whether immunotherapy might be used earlier, namely before the surgery. Christian Blank is indeed studying this. In the Netherlands Cancer Institute, under his leadership, a unique clinical study is being conducted on the effects of a so-called neo-adjuvant immune therapy, which patients are given before the surgery. The first outcomes are expected in the course of 2018.
Another step takes us back to the lab. It would be best to be able to predict in advance who would benefit from a treatment with pembrolizumab and who might better be given a different adjuvant treatment. 'For, every immune system is unique', says Blank. In a new study, he therefore tries to characterize tumours, from biopsies that have been donated by patients, according to their own specific immune-fingerprint.
'Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma, Christian Blank, Alexander van Akkooi et al. New England Journal of Medicine 15 April 2018
Alexander van Akkooi
Christian Blank and his research group
- watch the video about checkpoint inhibitors (in Dutch)
- also watch the video about immunotherapy in general (in Dutch)
- Name of the study: EORTC 1325/KEYNOTE-054