Low relapse risk after stopping PD-1 inhibitor therapy in melanoma

Skin cancers

5 Feb 2020

The risk of relapse is low in patients with advanced melanoma who have achieved complete remission (CR) on PD-1 inhibitors and subsequently elect to discontinue treatment.

An international study of 185 patients including Australians who discontinued treatment with either pembrolizumab or nivolumab – without indications such as disease progression or treatment-limiting toxicity – found overall 78% remained free of disease progression after a mean follow-up of 32 months.

Most of those (86%) who had achieved CR before discontinuation of the treatment remained disease free compared to 68% of patients who had a partial response (PR) and 50% of those with stable disease (SD).  

The median time on treatment with either of the PD-1 inhibitors was 12 months overall or 11 months for those with CR, 15 months for those with PR and 14 months for those with SD.

Most patients had previously been treated with ipilimumab (49%) or a BRAF-inhibitor (15%). In 43% of patients, the PD-1 inhibitor was a first-line therapy. 

The study found sites of progression after discontinuation were typically new lesions (65%) rather than progression at a previously existing metastatic site (35%).

The best objective response following relapse and retreatment with a PD-1 inhibitor was CR in 11% of patients, PR in 21% of patients and SD in 26% of patients. Almost a third (32%) did not respond to retreatment.

The study, published in Annals of Oncology, said the findings were consistent with other evidence that durable responses can be achieved after relatively short durations of other immunotherapies.  

The authors said it was important to establish guidelines for optimal treatment duration given patients could otherwise be left on treatment for longer than needed and exposed to the risk of treatment related adverse events.

“Secondly, unnecessary continuation of therapy is associated with a significant financial burden with drug costs, administration infrastructure and out-of-pocket expenses to patients.”

“Our study is the first to report treatment duration and outcome (including outcome after retreatment with anti-PD-1) after elective treatment discontinuation in a large real-world cohort of 185 advanced melanoma patients,” they said.

“We observed that the risk of PD following treatment discontinuation was significantly associated with best overall response, and significantly lower in patients with a CR.”

“Although the number of patients being retreated at the time of progression is relatively small (N = 19), our case series indicates, in line with the data from the KEYNOTE-006 trial, that retreatment can lead to renewed antitumour activity in a subset of patients after a treatment break.”

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