Study clarifies optimal duration of anti-PD-1 checkpoint inhibitor therapy


By Michael Woodhead

2 Apr 2019

Patients with advance melanoma may be able to discontinue treatment with anti-PD-1 therapy after six months with a low risk of relapse, according to findings from a real-world cohort that included Australian patients.

After a median follow up of 18 months after electively discontinuing pembrolizumab or nivolumab, 78% of patients remained free of progression, a retrospective study  of 185 patients with advanced melanoma found.

Disease progression was less frequent   in patients with a complete response (14%) at the time of discontinuing therapy, compared to those who were a partial response (32%) or stable disease, according to the findings published in Annals of Oncology.

In addition, six out of 19 patients (32%) who were retreated with anti-PD-1 therapy showed a new anti-tumour reponse, the study showed.

The study authors said that in real world settings treatment with PD-1 blockers was of a shorter duration than in clinical trials such as KEYNOTE-001, and the optimal duration of therapy has not been established.

Duration of therapy had been arbitrarily set at two years or until disease progression or treatment-limiting toxicity, but experience from trials had suggested that patients experienced ongoing benefit after discontinuing therapy earlier.

In the cohort under evaluation, the media treatment exposure was 12 months and the best objective tumour response at the time of discontinuation was complete response in 63% of patients, partial response in 24% and stable disease in 9% of patients. Overall, 78% of patients remained free of progression at a median 18 months after discontinuation.

The researchers said it was notable that among the patients with a complete response the risk of progression after discontinuation was significantly higher for those treated for less than 6 months, with a median progression free survival of 18.9 months versus not reached for patients treated for more than 6 months.

There was no difference in risk of disease progression between patients with complete response treated for 6 to 12, 12 to 18, 18 to 24 or more than 24 months.

The researchers said the findings showed that further investigation into the optimal duration of therapy was warranted,  elective discontinuation was common in real world settings.

“Continuing therapy means that patients remain at risk of treatment related adverse events, which may affect quality of life. Secondly, unnecessary continuation of therapy is associated with a significant financial burden with drug costs, administration infrastructure, and out-of-pocket expenses to patients,” they wrote.

Other predictors that may help treatment discontinuation decisions included complete metabolic tumour response on FDG-PET/CT at one year and measurement of circulating tumour DNA, they added.

“Our data can help guide the design of future prospective clinical trials examining this important issue,” concluded the study authors, who included oncologists from Princess Alexandra Hospital and Greenslope Private Hospital, Brisbane, Melanoma Institute Australia and the University of Sydney and the Northern Sydney Cancer Centre, Royal North Shore Hospital, Mater Hospital, Sydney.

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