Patients With Melanoma Treated With Anti–PD-1 Antibodies Beyond RECIST Progression
A pooled analysis by the U.S. Food and Drug Administration (FDA) has shown a benefit of treatment beyond progression, as defined by RECIST criteria, in many patients receiving anti–programmed cell death protein 1 (PD-1) antibodies for unresectable or metastatic melanoma. The analysis was reported in The Lancet Oncology by Beaver et al.
Study Details
The study included data from all submissions of trial reports and data to the FDA in support of applications for anti–PD-1 antibodies used alone or in combination in the treatment of unresectable or metastatic melanoma that allowed for continuation of antibody treatment beyond RECIST v1.1–defined progression in the anti–PD-1 group and that were approved by the FDA before January 1, 2017.
Individual patient data were pooled for patients who received at least one dose of an anti–PD-1 antibody in the included trials. Any patient receiving anti–PD-1 antibody after RECIST-defined progression date was included in the treatment beyond progression cohort. Treatment beyond progression response was defined as a decrease in target lesion tumor burden (sum of reference diameters) of ≥ 30% from the time of RECIST-defined progression that did not require confirmation at a subsequent assessment.
Outcomes With Continued Treatment
A total 2,624 patients from 8 multicenter trials were included in the analysis. A total of 1,361 (52%) had progressive disease on RECIST criteria; of these, 692 (51%) continued anti–PD-1 antibody treatment beyond progression and 669 (49%) did not.
Among 500 patients in the treatment-beyond-progression cohort who were evaluable for response, 95 (19%) exhibited ≥ 30% decrease in tumor burden from the time of RECIST-defined progression; the 95 patients with such response represent 14% of the total of 692 patients treated beyond progression and 4% of all 2,624 patients receiving anti–PD-1 antibodies. Among patients with RECIST-defined progression, median overall survival was 24.4 months in the treatment-beyond-progression cohort vs 11.2 months in the no-treatment-beyond-progression cohort.
Adverse Event Profile
Serious adverse events within 90 days after treatment discontinuation occurred in 362 (54%) of the treatment-beyond-progression cohort vs 295 (43%) of the no-treatment-beyond-progression cohort. Immune-related adverse within 90 days after discontinuation occurred in 78 (11%) vs 106 (16%) patients.
The investigators concluded, “Continuation of treatment beyond progression in the product labelling of these immunotherapies has not been recommended because the clinical benefit remains to be proven. Treatment beyond progression with anti–PD-1 antibody therapy might be appropriate for selected patients with unresectable or metastatic melanoma, identified by specific criteria at the time of progression, based on the potential for late responses in the setting of the known toxicity profile.”
The investigators reported no funding for the study.
Julia A. Beaver, MD, of the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research at the FDA, is the corresponding author for The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
