Purpose
SABR is a locally effective modality for metastatic renal cell carcinoma (RCC) (1,
2).
Preclinical data in RCC has demonstrated improved disease control in both irradiated and unirradiated sites with single fraction SABR and anti-PD1 checkpoint blockade (3),
although prospective clinical trials with this combination have not yet been reported.
Methods and materials
RAPPORT is a single arm,
phase 1b/II clinical trial (NCT02855203).
Patients with 1-5 oligometastases from clear cell RCC were eligible.
They received a single fraction SABR of 18-20Gy to all metastases (or 30Gy in 10 fractions of conventional radiotherapy if SABR was not feasible) followed by 8 x 3 weekly cycles of 200mg intravenous pembrolizumab.
This is a preplanned interim safety analysis of the first 12 patients who completed SABR and 12 weeks of pembrolizumab.
Adverse events were graded using CTCAE v4.0.
Results
The mean age was 62 years,
with 7 males and 5 females enrolled.
In total 37 metastases were irradiated,
with 32 (86%) receiving SABR and 5 (14%) receiving conventional radiotherapy.
The number of lesions per patient was 1 in 3 patients (25%),
3 in 4 patients (33%),
4 in 3 patients (25%) and 5 in 2 patients (17%).
The predominant site of metastases was the lung (n=24,
65%).
No treatment courses were abandoned due toxicity,
although one patient ceased treatment early due to progressive disease....
Conclusion
The combination of SABR + pembrolizumab in a small cohort of patients to date is well tolerated.
Based on this the independent safety monitoring committee have recommended continuation of planned recruitment (n=30).
Personal information
Shankar Siva is a radiation oncologist and NHRMC ECF fellowship holder at the Peter MacCallum Cancer Centre.
He chairs the SABR service there and is the PI of multiple investigator initiated prospective clinical trials.
References
1. Siva S,
Kothari G,
Muacevic A,
Louie AV,
Slotman BJ,
Teh BS,
et al.
Radiotherapy for renal cell carcinoma: renaissance of an overlooked approach.
Nat Rev Urol.
2017;14(9):549-63.
2. Kothari G,
Foroudi F,
Gill S,
Corcoran NM,
Siva S.
Outcomes of stereotactic radiotherapy for cranial and extracranial metastatic renal cell carcinoma: a systematic review.
Acta oncologica.
2015;54(2):148-57.
3. Park SS,
Dong H,
Liu X,
Harrington SM,
Krco CJ,
Grams MP,
et al.
PD-1 Restrains Radiotherapy-Induced Abscopal Effect.
Cancer immunology research.
2015;3(6):610-9.
