Some patients with unresectable or metastatic melanoma who receive immunotherapy and continue therapy after progression have decreased tumor burden, and survival is improved when the therapy is continued as well, according to a new pooled analysis.
Since the approval of immune therapies for melanoma, concerns have been raised regarding the adequacy of standard RECIST criteria to identify responses and progression. “Patients who receive immunotherapy might develop an atypical response pattern, wherein they initially meet conventional response criteria for progressive disease but later have decreases in tumor burden,” wrote study authors led by Julia A. Beaver, MD, of the US Food and Drug Administration in Silver Spring, Maryland.
To assess the clinical benefit in patients who continue immunotherapy beyond traditionally defined progression, the investigators conducted a pooled analysis of eight multicenter clinical trials totaling 2,624 patients. All patients had unresectable or metastatic melanoma, and all included trials allowed for continuation of the anti–PD-1 antibody beyond RECIST-defined progression. The studies included three KEYNOTE trials (P001, P002, and P006) and five CheckMate trials (0035, 037, 066, 067, 069); the results were published online ahead of print in Lancet Oncology.
Among the full cohort, 1,361 patients (52%) had progressive disease, and 692 of those patients (51%) received continued anti–PD-1 therapy beyond the point of progression. Of those patients treated beyond progression, 19% of evaluable patients had a 30% or more decrease in tumor burden when using RECIST-defined progression as the reference point. This represented 14% of all those treated beyond progression, and 4% of the entire cohort treated with the immunotherapy agents.
Patients with progressive disease who were treated beyond progression had a median overall survival of 24.4 months, compared with 11.2 months in those who were not treated after progression; those in the full cohort with no disease progression had a median overall survival of 32.5 months.
In those who were not treated after progression, 54% had a serious adverse event up to 90 days after treatment discontinuation. In the group with those treated beyond progression, 43% had a serious adverse event.
“In this pooled analysis, although more than half of patients with unresectable or metastatic melanoma with RECIST-defined progression received continued anti–PD-1 antibody treatment beyond progression, only a modest number of these patients seemed to have subsequent decreases in their target lesion tumor burden that reached the level of a response in our analysis,” the authors concluded. They noted that questions still remain regarding the clinical benefit of this approach, and “as such, continuation of treatment beyond progression in the product labeling of anti–PD-1 antibody therapies has not been recommended.”