A phase II multicenter study of stereotactic radiotherapy (SRT) for oligoprogression in metastatic renal cell cancer (mRCC) patients receiving tyrosine kinase inhibitor (TKI) therapy.

Abstract

5065 Background: SRT is increasingly considered to delay the need to change systemic therapy in metastatic cancer patients who develop oligoprogression. This prospective phase II study evaluated the use of SRT in the setting of mRCC patients who developed oligoprogression while on 1st or 2nd line TKI therapy. Methods: IMDC favourable or intermediate risk mRCC patients (pts) who had previous stability or response on ≥ 3 months of TKI therapy were eligible if they developed radiographic progression of ≤ 5 metastases. The oligoprogressive tumours were treated with SRT while other metastases which were stable or responding to TKI therapy were left alone. TKI therapy was temporarily stopped during SRT, and the same TKI drug then resumed. Endpoints included local control of the irradiated lesions, progression free survival (PFS), overall survival (OS), and cumulative incidence of changing systemic therapy after study entry. Results: 37 pts (median age 63, IMDC favourable 12, intermediate 25) with 57 oligoprogressive tumours were enrolled. 35 pts were on sunitinib and 2 on pazopanib. Median duration of TKI therapy prior to study entry was 18.6 months. 4 pts had IL-2 therapy prior to a 2nd line TKI. 21 pts had a solitary oligoprogressive tumour, while 17 pts had 2-3 oligoprogressive tumours treated with SRT. Median biological effective dose (BED10) was 72 Gy, corresponding to an SRT dose of 40 Gy in 5 fractions. Irradiated tumour sites were the following: 21 lung/pleural, 15 bone, 7 lymph node, 4 adrenal, 4 liver, 3 brain, 2 spleen, and 1 pancreas. At a median followup of 11.6 (1.8-53.5) months the median PFS from study entry was 9.6 months (95%CI 7.4-20.5) with the vast majority of progression occurring outside of the irradiated areas. The 2-year local control of the irradiated tumours was 96%. The 2-year OS from study entry was 77%. The cumulative incidence of changing systemic therapy was 47% at 1 year and 75% at 2 years, with a median time to a change in systemic therapy of 12.6 months. There were no grade 3-5 SRT related toxicities. Conclusions: To our knowledge, this is the first prospective evaluation of the use of SRT for oligoprogressive metastatic cancer. Local control of irradiated oligoprogressive mRCC tumours was high. After delivering SRT, mRCC patients did not need a change in their systemic therapy for a median of 1 year, effectively increasing the PFS of their TKI therapy. This novel approach should be studied in patients with oligoprogression on immunotherapy. Clinical trial information: NCT02019576 .

Management of advanced kidney cancer: Kidney Cancer Research Network of Canada (KCRNC) consensus update 2021

“…A Canadian phase 2 trial of using SBRT in 37 mRCC patients with oligoprogression while on sunitinib or pazopanib has been reported in abstract form. 95 At a median followup of 11.6 (1.8-53.5) months, the median PFS from study entry was 9.6 months (95% CI 7.4-20.5), with the vast majority of progression occurring outside of the irradiated areas. The two-year local control of the irradiated tumors was 96%.…”

“…Such an approach has previously been studied primarily in metastatic non-small-cell lung cancer patients who developed oligoprogression while on TKIs. 95…”

Stereotactic Ablative Radiation Therapy for Oligoprogressive Renal Cell Carcinoma

“…21 A prospective phase II study investigating SAbR treatment of 37 patients with oligoprogressive RCC was recently reported, and revealed a 9.6 months mPFS, which is comparable to our findings (NCT02019576). 30 One challenge to deploying SAbR for oligoprogression is identifying the patient population most likely to benefit. In our study, oligoprogressive patients treated with SAbR while on an ICI-containing regimen appeared to have better mPFS than those receiving either vascular endothelial growth factor or mTOR inhibitors.…”

Stereotactic radiotherapy for oligoprogressive ER-positive breast cancer (AVATAR)

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