Concurrent administration of checkpoint inhibitors and radiotherapy (Immuno-RT) remains investigational and is the subject of multiple clinical trials. Nivolumab is an anti-programmed death-1 receptor monoclonal antibody that exhibits checkpoint-mediated immune response against tumor cells. Nivolumab has received regulatory approval for the second-line management of metastatic non-small cell lung cancer (NSCLC) & renal cell carcinoma (RCC). Ionising radiation could increase the diversity & quantity of tumoral antigen presentation, thereby augmenting anti-tumour immune response achieved with checkpoint inhibitors. The aim of this study was to assess the efficacy & toxicity of concurrent administration of nivolumab and radiotherapy.
We identified 6 patients that received concurrent nivolumab and radiotherapy to 19 lesions; metastatic NSCLC (n = 4), metastatic RCC (n = 2). Treatment-related toxicities were identified by retrospective review of patient notes. Measurable lesions were assessed by RECIST 1.1 criteria. Pain score was used to assess symptomatic responses.
Stereotactic and conformal radiotherapy were delivered to 9 and 10 lesions, respectively. Treatment sites (number of lesions): lung (n = 8), hip (n = 3), brain (n = 4), shoulder, scalp, ethmoid and adrenal. The gap between radiotherapy & nivolumab did not exceed 2 weeks for all patients. No grade 3-4 toxicities were observed. Two of the lung cancer patients developed grade 1 pneumonitis. Fractionation schedules included 48Gy/4 fractions (#), 40Gy/4#, 34Gy/4#, 22Gy/1#, 30Gy/10#, 25Gy/5#, 20Gy/4# and 20Gy/5#. Of the 14 measurable lesions, 86% had excellent response including complete response of 3 lesions. Symptomatic benefit was observed in 4 out of 6 treatment sites (66%).
The of role of concurrent nivolumab & radiotherapy in patients with metastatic NSCLC and RCC has never been reported previously. In our study, concurrent administration of nivolumab and radiotherapy appears to be well tolerated with excellent radiological and symptomatic responses. Ongoing clinical trials may help determine the future role of Immuno-RT in the rapidly evolving treatment paradigm of metastatic NSCLC and RCC management.
Clinical trial identification
Legal entity responsible for the study
J. Ansari: Paid honoraria for lectures and/or advisory boards for Amjen, AstraZeneca, Pfizer, Novartis, Boehringer Ingleheim, Bristol-Myers Squibb, Roche and Sanofi. A. Shaukat: lecture fees and advisory board for Bristol-Myers Squibb. A. Alhamad: Advisory board for Bristol-Myers Squibb. All other authors have declared no conflicts of interest.