Neoadjuvant nivolumab tested for metastatic RCC
medwireNews: Results from the ADAPTeR study suggest that giving nivolumab before and after cytoreductive nephrectomy or metastatic biopsy may be a feasible strategy for patients with treatment-naïve metastatic clear cell renal cell carcinoma (RCC).
The trial findings were presented in a poster at the ESMO Congress 2019 in Barcelona, Spain, by Lewis Au (Francis Crick Institute, London, UK) and co-authors, who say that the phase II study is the first to evaluate neoadjuvant PD-1 inhibitor therapy in this setting.
Fifteen patients were given four cycles of nivolumab 3 mg/kg every 2 weeks before undergoing either nephrectomy, where feasible, or multiple biopsies at their metastatic sites, followed by nivolumab therapy until progressive disease.
Thirteen patients experienced a treatment-related adverse event, including grade 3–4 events in four patients but the investigators say there were “no new safety signals relating to nivolumab”.
At the time of data cutoff, the participants had been followed-up for a median of 12.5 months and five patients were continuing with nivolumab therapy, with 66% having discontinued because of progressive disease.
The RECIST objective response rate was 27%, with four patients achieving a partial response and a further seven patients had stable disease.
Ad hoc analysis gave a median progression-free survival of 4.1 months, with durations of 4.1, 3.4 and 9.6 months for patients with poor, intermediate and favorable IMDC classifications, respectively. The corresponding rates for overall survival were 17.5 months, and 15.7, 13.2 and 24.3 months.
Of the nine patients who were not considered clinically suitable for nephrectomy after initial nivolumab treatment, four showed primary tumor shrinkage of between 2% and 33%.
The study design included use of multiregion biopsies at baseline, week 9, and at time of progressive disease, allowing whole-exome sequencing and evaluation of the tumor immune microenvironment, the team explains.
Preliminary analysis of 30 tumor samples for 60 gene expression markers in 14 immune cell populations revealed “heterogeneous tumor expression” with both hot (infiltrate) and cold (no infiltrate) sites. For example, one patient had four “cold” samples taken from two sites in the primary tumor and two metastatic sites, but also one “hot” sample from the primary site.
Furthermore, the investigators found that “[i]mmune infiltration status at baseline shows a general clustering for pre-existing immune infiltration (‘hot’) that appears to correlate with therapy response, where patients tended to derive clinical benefit for >6 months on treatment.”
They continue: “Most, but not all, on-treatment biopsies demonstrated similar infiltration patterns compared to baseline.”
Analyses of T-cell subsets and genomic analysis is ongoing in the study population, the authors add.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
This independent news article was supported by an educational grant from Pfizer and Merck KGaA