Systemic Therapy after IO-VEGF

Several therapeutic combinations of immune-oncology (IO) plus vascular endothelial growth factor (VEGF) regimens have demonstrated positive results in phase 3 trials. However, according to Yasser Ged, MBBS, MRCP, and colleagues, there are few data available on outcomes to subsequent therapy in patients on IO-VEGF combination regimens with disease progression.

The researchers conducted a retrospective analysis on patients with advanced clear cell renal cell carcinoma (ccRCC) at the Memorial Sloan Kettering Cancer Center and Cleveland Clinic Cancer Institute. Eligible patients had initiated systemic therapy post IO-VEGF regimens, including combinations with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (IO-TKI) and combinations with anti-VEGF monoclonal antibodies (IO-mAB).

The primary objective of the analysis was an evaluation of overall survival post IO-VEGF. Secondary objectives included objective response rate (ORR) and progression-free survival, measured by Response Evaluation in Solid Tumors Criteria, version 1,1. Time from the start of systemic therapy post-IO-VEGF to the event of interest was evaluated using Kaplan-Meier methods and log-rank test.

A total of 59 patients were treated following discontinuation of IO-VEGF regimens. Of those 59% (n=35) received  IO-mAB and 41% (n=24) received IO-TKI. International Metastatic RCC Database Consortium scores at the start at the next line of therapy were favorable in 20% of the patients, intermediate in 60%, and poor in 20%.

The next line of therapy included VEGFR-TKI monotherapy in 76% of the cohort (n=45), mammalian target of rapamycin inhibitors in 5% (n=3), and unreported clinical trials in 9% (n=5). Regimens that contained VEGFR-TKI (n=51) included cabozantinib (n=22), axitinib (n=17), lenvatinib/everolimus (n=4), pazopanib (n=4), and others (n=4).

Median overall survival was 24.5 months; 12-month overall survival rate was 63%. The ORR was 27% (n=14/51) and median progression-free survival was 6.8 months. In comparison of IO-TKI with IO-mAB, there was no difference in post IO-VEGF overall survival (log rank p=.07).

“Post combination IO-VEGF treatment, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs continue to show clinical activity similar to historic experiences of patients post VEGF monotherapy,” the researchers said.

Source: Ged Y, Gupta R, Duzgol C, et al. Systemic therapy for advanced clear cell renal cell carcinoma (ccRCC) after progression on immune-oncology plus VEGF targeted therapy combinations (IO-VEGF). Abstract of a poster presented at the American Society of Clinical Oncology 2019 Annual Meeting, June 3, 2019, Chicago, Illinois.