HMRI and University of Newcastle researchers have discovered that treating patients who have late-stage treatment resistant melanoma with a combination of two existing drugs significantly increases their survival times.
Led by Professor Nikola Bowden and Dr Andre van der Westhuizen from HMRI’s Drug Repurposing and Medicines Research program, the project’s findings have been published in the American Association for Cancer Research journal Cancer Research Communications.
The drug repurposing trial focused on patients with end stage melanoma whose cancers had become resistant to frontline immunotherapy treatment, a class of drugs known as Immune Checkpoint Inhibiters (ICB). ICBs interfere with a cancer cells’ ability to ‘hide’ from the body's immune system allowing a patient’s own body to fight the cancer.
The team found that by treating patients with a combination of two already approved chemotherapy drugs, Azacitidine and Carboplatin, they were able to re-sensitise the cancer cells to ICB treatment.
Professor Bowden said the study provided a potential new treatment for patients who, until now, had run out of options
“In this paper we have shown in a phase II study that treatment with Azacitidine and Carboplatin could be effective in priming for anti-immunotherapy (Avelumab) in patients with advanced ICB-resistant melanoma,” Professor Bowden said.
The team has been investigating these drugs since 2015 and, between 2017 and 2021, 20 patients, were given the two repurposed chemo drugs in order to ‘prime’ them for a subsequent immunotherapy treatment.
The patients survived an average of 47 weeks, with four of the patients still alive today following the treatment they received in the trial.
“For some of the patients, it was like the tumours were frozen in time and they stayed the same for a very long time. Some patients even experienced a reduction in tumour size and number,” Professor Bowden said.
The drug repurposing trial was combined with a new form of immunotherapy.
Professor Bowden explains: “Melanoma cells send out a signal to the immune system that says, ‘I’m meant to be here’. The chemo drug combination we used mobilise the immune system to attack the tumours while the immunotherapy blocks that signal.”
This trial was initially funded by the Hunter Melanoma Foundation and generous community donations, including a $20,000 donation from the late Valerie Ryan.
The second stage of clinical trials are underway using updated immunotherapy drugs.
“Initial results suggest that this group of patients are doing even better on the new drugs,” Professor Bowden said.
To read the American Association for Cancer Research Journal article, click here.
* HMRI is a partnership between the University of Newcastle, Hunter New England Health, and the community.
Cancer Research Communications
Method of Research
Randomized controlled/clinical trial
Subject of Research
Repurposing Azacitidine and Carboplatin to Prime Immune Checkpoint Blockade–resistant Melanoma for Anti-PD-L1 Rechallenge
Article Publication Date