Skin cancers

Controversy debate: neoadjuvant vs adjuvant therapy in melanoma


The use of neo-adjuvant therapy as standard care in people with locoregional and oligometastatic melanoma looks promising but it is not yet ready for prime time, concludes a ‘controversy’ debate that pitted neo-adjuvant against adjuvant or combination therapy. 

At the opening of the session European Society of Medical Oncology (ESMO) Congress  2019 delegates were asked if neoadjuvant therapy in patients with resectable melanoma provided an advantage over adjuvant therapy: 44% voted ‘yes’, 41.3% ‘don’t know’, and  14.7% ‘no’.

Taking to the podium to debate the pros of neo-adjuvant therapy, surgical oncologist Dr Alexander van Akkooi from the Netherlands Cancer Institute noted that neo-adjuvant and adjuvant therapy have the same goal – to treat residual undetectable micrometastatic (either regional or distant) disease.  

“The order of treatment is simply the difference, in case of adjuvant it is given after surgery and in case of neo-adjuvant you start with systemic therapy first,” he said. 

Both options had their pros and cons – adjuvant therapy had less toxicity and there were large phase 3 randomised controlled trials that showed strong evidence for the approach. 

However, the advantages of neo-adjuvant therapy were that treatment had a shorter duration, relapse-free survival was typically increased and there was also the potential to reduce the extent of surgery and tailor further treatment.

Results from the OPACIN-NEO trial, the NADINA trial as well as a pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC) all pointed to the fact that neo-adjuvant therapy was looking “very promising” in the melanoma setting, Dr Akkooi said. 

However, he conceded that more studies would be needed, as well as phase III prospective RCTs to evaluate neo-adjuvant versus node dissection followed by one year of anti-PD-1. 

He added that in November the INMC were due to meet with the FDA to ask if they would accept pathological complete response as a primary endpoint to register for neo-adjuvant therapy trials.

“This will allow for rapid testing of various drugs or combinations of drugs,” he said. 

Pros of adjuvant and combination therapy

Taking to the podium to argue for adjuvant and combination therapy, Dr Mario Mandala from the Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy agreed that neo-adjuvant therapy was promising in the treatment of melanoma but said that he believed it was not ready for “prime time”. 

Unlike neo-adjuvant therapy, the use of adjuvant therapy in melanoma was based on “fact and not hope” he quipped, and this was evident from adjuvant trials such as two EORTC trials led [here and here] by Alexander M. Eggermont and colleagues.

“With neo-adjuvant therapy, patients who do not respond may not have curative surgery which is the standard of care, and there is a risk of toxicity which can cause surgical complications as well as logistical issues with patient management,” he told delegates.

Nevertheless, he said the rationale for neo-adjuvant therapy in this setting was biologically strong. 

“There is some clinical data that shows that there is improved efficacy of neo-adjuvant therapy compared to adjuvant therapy but we need to test this in other clinical studies,” he noted. 

“We need to share ideas, combine knowledge of academia with companies and we need to standardise our approach in science and more phase 3 randomised trials of neo-adjuvant versus adjuvant are needed,” he concluded. 

After the debate: Neo-adjuvant therapy in patients with resectable melanoma provides an advantage over adjuvant therapy: 73% voted ‘yes’, 15.6% ‘don’t know’ and 11.5% ‘no’

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