ASCO GU 2020: Combined Dual Checkpoint Inhibition and Stereotactic Body Radiotherapy in the Metastatic Renal Cell Carcinoma Setting (RADVAX RCC).
At the Oral Abstract Session on Renal Cell Carcinoma at the 2020 Genitourinary Cancers Symposium, Dr. Hans Hammers presented preliminary results of the RADVAX RCC trial, a single-arm trial in which patients with mRCC were treated with SBRT in combination with dual immune checkpoint inhibition with ipilimumab and nivolumab.
Patients with metastatic RCC with at least 2 metastatic sites who had received either no prior therapy, a TKI, or cytokines were enrolled. These patients received a combination of nivolumab and ipilimumab every 3 weeks according to the standard of care for 4 cycles during an “induction phase” followed by nivolumab alone indefinitely during a maintenance phase. (Nivolumab was initially given every 2 weeks but this was amended to every 4 weeks after a protocol amendment.) 1-2 metastatic sites were treated with SBRT in either 40 or 50 gy in 5 fractions. The outcomes of interest were objective response rate in non-irradiated lesions according to RECIST 1.1 as well as safety and tolerability.
A total of 25 patients were enrolled (out of only 29 screened from March 2017 – March 2019) at a single site. (A second site was approved but did not enroll any patients during the trial period.) 16% of patients had received IL2 previously and 26% had received a TKI previously. (None had received both.) 80% of patients were intermediate risk, 12% poor risk, and 8% favorable risk. 68% of patients had undergone nephrectomy. The median baseline sum of the longest diameters (SLD) of non-irradiated target lesions for use in determining response was 7.6cm.
In terms of efficacy, 56% of patients experienced a partial response (defined as a 30% reduction in SLD per RECIST 1.1), 24% had stable disease, and 16% had disease progression. (Data was missing from one patient.) Median progression-free survival was 8.2 months (95% CI 4.6-18.0) and the 12 month PFS rate was 36% (95% CI 0.18 – 0.54). These numbers are similar to those seen in Checkmate-214, in which patients randomized to nivo/ipi had a median PFS of 11.6 months and an objective response rate of 42%.
Quantitative data of response in the irradiated lesions was not presented, however, Dr. Hammers noted that large reductions in tumor volume were generally seen. This includes some cases where the primary tumor was still in place and was chosen as the radiation target.
In terms of safety, these were also similar to what would be expected from nivo/ipi alone. 36% of patients suffered grade 3-4 adverse events (again similar to the 46% seen in the nivo/ipi arm of Checkmate 214). There was only one case of toxicity related directly related to radiation, which was a case of pneumonitis.
Overall the safety results of this trial are encouraging. There is no strong signal so far that SBRT improves survival over nivo/ipi alone, however, this trial was not powered to provide such evidence.
Dr. Hammers concluded by suggesting that of SBRT might be particularly beneficial when used to specifically target metastatic lesions that are immunologically “cold”, which would both treat the individual lesions and potentially increase immune targeting of those cell lines. A future version of this study may incorporate this feature into its design.
Presented by: Hans J Hammers, MD, PhD, Associate Professor, and Medical Oncologist, University of Texas Southwestern Medical Center, Dallas, Texas
Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA @mcstroth at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
References:
1. Twyman-saint victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520(7547):373-7.