Recent reports have described the safety and clinical utility of combining anti-PD1 checkpoint inhibition with radiotherapy. Abscopal effects - radiotherapy inducing clinically meaningful distant responses in unirradiated sites - have been hypothesized, though clinical proof is scarce.
We analyzed efficacy and toxicity of combined stereotactic ablative radiotherapy (SABR) and anti-PD1 in consecutive melanoma and non-squamous cell lung cancer (NSCLC) patients that underwent stereotactic radiotherapy for a limited number of growing metastases during anti-PD-1 in our institute since January 2017.
Ten patients, 8 with metastatic melanoma and 2 patients with metastatic NSCLC, were included in this series. SABR was given at a median of 11,5 months (range 3-21 months) after the start of anti-PD1 treatment (nivolumab or pembrolizumab). A single metastasis was irradiated in 8 patients, 2 simultaneously in 1 patient and 3 in the last patient. Disease control of the irradiated lesion was established in all 10 patients. With a median follow-up of 5,5 months (range 1-16 months) all patients were still alive without the need to start a subsequent systemic therapy. Additionally, abscopal effects, defined as a significant decrease of unirradiated metastases that were previously stable under immunotherapy, were seen in 4/10 patients after SABR. One patient developed a pneumonitis (outside high dose radiation field) shortly after SABR that was considered to be related to nivolumab. No other severe toxicities of the combined treatments were observed.
These data show that combining SABR and checkpoint inhibition for patients with oligo-progressive disease during PD1-inhibition is a strategy that can induce long-term disease control and additionally can lead to abscopal effects in unirradiated tumor sites. In order to explore feasibility for all patients with oligo-progressive disease during PD1-inhibition, prospective clinical studies are needed.
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University Medical Center Utrecht.
Has not received any funding.
K.P. Suijkerbuijk: Consulting, Advisory relationship: Bristol-Myers Squibb, MS; Honoraria (institution): Novartis, Roche. G. Groenewegen: Consulting, Advisory relationship: BMS, MSD; Speakers fee: Astellas; Honoraria received paid to institution. All other authors have declared no conflicts of interest.