Certain patients with advanced melanoma treated with pembrolizumab had unique response patterns, such as early or delayed tumor pseudoprogression, and Response Evaluation Criteria in Solid Tumors (RECIST) criteria might underestimate the immunotherapy benefit in this subset.

Among 592 patients who survived 12 weeks or more, 84 (14%) had progressive disease per RECIST v1.1 but nonprogressive disease per immune-related response criteria (irRC). Overall survival (OS) was longer in this group compared with the 177 patients who had progressive disease per both RECIST v1.1 and irRC: median OS was 22.5 months (95% CI, 16.5 to not yet reached) vs. 8.4 months (95% CI, 6.6 to 9.9), investigators reported (J Clin Oncol. 2016 March 7. doi: 10.1200/JCO.2015.64.0391).

“RECIST v1.1 might underestimate the benefit of pembrolizumab in approximately 15% of patients. 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. Furthermore, clinicians aware to these criteria might be able to avoid otherwise premature termination of potentially effective treatment,” wrote Dr. F. Stephen Hodi Jr., director of immuno-oncology at Dana Farber Cancer Institute, Boston, and colleagues.

Two-year OS rates for patients with nonprogressive disease per both criteria, progressive disease per RECIST v1.1 and nonprogressive disease per irRC, and progressive disease per both criteria were 77.6%, 37.5%, and 17.3%, respectively.

Conventional response criteria such as RECIST might underestimate benefit of immune checkpoint blockade, such as ipilimumab and pembrolizumab, because objective response and prolonged disease stabilization can occur after an initial increase in tumor burden or new lesions. To better characterize atypical response patterns observed in trials of ipilimumab in melanoma, irRC were developed, where the initial evidence of disease progression is handled differently. The current study retrospectively examined responses from KEYNOTE-001 melanoma expansion cohorts, which enrolled 655 patients with advanced melanoma; 327 had 28 weeks or more of imaging follow up and were eligible for atypical response analysis.

In total, 24 of 327 patients (7.3%) had atypical responses, including 15 (4.5%) with early pseudoprogression and nine (2.8%) with delayed pseudoprogression. Patterns of atypical response included regression of tumor burden and stable disease despite the development of new lesions, and initial increases in the size of target lesions followed by decreases without evidence of new lesions.

The irRC uses bidimensional tumor measurements, which introduce greater variability than unidimensional measurements. In addition, the investigators note that irRC may not fully capture all patterns of clinical response to immunotherapies.

“Given the rapid development of effective immuno-oncology agents in multiple cancers, there is a growing effort to develop new standard response criteria for patients treated with immunotherapy to provide for robust clinical end points in evaluating these new treatments,” the investigators wrote.



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