NEW YORK (Reuters Health) - Some patients with advanced melanoma treated with pembrolizumab have atypical response patterns, and conventional Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) may underestimate the benefit of the drug in these patients, new findings hint.
Clinicians who are aware of this might be able to avoid otherwise premature termination of potentially effective treatment, Dr. F. Stephen Hodi of Dana Farber Cancer Institute, Boston, told Reuters Health by email.
The findings, online March 7 in the Journal of Clinical Oncology, stem from an analysis of data from the KEYNOTE-001 study.
Among 655 patients treated with pembrolizumab in the study, 327 had at least 28 weeks of imaging follow-up and 24 of these patients (7%) atypical responses, including 15 (5%) with early pseudoprogression and nine (3%) with delayed pseudoprogression.
Among 592 patients who survived at least 12 weeks, 84 (14%) had progressive disease based on RECIST v1.1 but nonprogressive disease based on immune-related response criteria (irRC).
At two-years, overall survival rates were 77.6% in patients with nonprogressive disease per both criteria, 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC and 17.3% in patients with progressive disease per both criteria.
"Although relatively infrequent, these unique response patterns have important potential implications for patient management, which is particularly true given observed differences in survival by RECIST v1.1 and irRC per central review," the authors write.
The 84 patients with progressive disease by RECIST v1.1 but nonprogressive disease by irRC had a longer overall survival (22.5 months) than the 177 patients with progressive disease per both criteria (8.4 months), "which suggests that RECIST v1.1 might underestimate the benefit of pembrolizumab in approximately 15% of patients," they note.
"These data suggest that patients may benefit from receiving treatment beyond initial evidence of radiographic progression and thus support the use of modified response criteria on the basis of immune-related response patterns," the authors say.
"RECIST v1.1, the conventional criteria for tumor measurement," they explain, "provide a simple, standardized method for defining the therapeutic effect of chemotherapeutic agents. The use of unidimensional tumor measurements facilitates their application while minimizing variability, but they are unable to capture responses that occur after disease progression, which might limit their usefulness when assessing response to immunotherapeutic agents. The irRC were developed to provide standardization for assessing response to immunotherapeutic agents."
"Prospective evaluations of irRC and RECIST v1.1 for patients who receive pembrolizumab and other immunotherapeutic agents are needed," they conclude.
The study was supported by Merck & Co. Several authors reported financial ties to Merck and other drug companies.
J Clin Oncol 2016.