ESTRO 2021 Abstract Book

S490

ESTRO 2021

Proffered papers: Proffered papers 37: Immuno and targeted agents

OC-0625 Immuno-radiotherapy in solid tumors: preliminary results of the randomized phase 2 CHEERS trial M. Spaas 1,2 , N. Sundahl 1,2 , S. Rottey 3,2 , V. Kruse 4 , D. De Maeseneer 3,5 , F. Duprez 1 , P. Dirix 6 , V. Surmont 7 , Y. Lievens 1,2 , R. Van den Begin 8 , D. Van Gestel 8 , V. Renard 9 , D. Reynders 10 , E. Goetghebeur 10 , P. Ost 6,2 1 Ghent University Hospital, Radiation Oncology, Ghent, Belgium; 2 Ghent University, Cancer Research Institute Ghent (CRIG), Ghent, Belgium; 3 Ghent University Hospital, Medical Oncology, Ghent, Belgium; 4 AZ Nikolaas, Medical Oncology, Sint-Niklaas, Belgium; 5 AZ Sint-Lucas, Medical Oncology, Bruges, Belgium; 6 Iridium Cancer Network, Radiation Oncology, Wilrijk, Belgium; 7 Ghent University Hospital, Pulmonary Medicine, Ghent, Belgium; 8 Jules Bordet Institute, Radiation Oncology, Brussels, Belgium; 9 AZ Sint-Lucas, Medical Oncology, Ghent, Belgium; 10 Ghent University, Applied Mathematics, Computer Science and Statistics & Stat-Gent, Ghent, Belgium Purpose or Objective Immune checkpoint blockade (ICB) has improved the outcome for many cancer types, but the majority of patients fails to respond to ICB monotherapy. Stereotactic body radiotherapy (SBRT) has the potential to improve the therapeutic ratio of ICB. We aimed to assess the addition of SBRT to ICB as compared to ICB monotherapy in patients with advanced solid tumors. Materials and Methods This multicenter randomized, open-label phase II trial was conducted in 4 Belgian hospitals. Patients with locally advanced or metastatic disease were randomly assigned (1:1) to receive anti-PD-(L)1 ICB alone as per standard of care (control arm) or combined with SBRT 3 x 8 Gy to a maximum of 3 lesions prior to the second or third ICB cycle, depending on the frequency of administration (experimental arm). Randomization was stratified according to tumor histology (melanoma, RCC, urothelial carcinoma, HNSCC, NSCLC) and disease burden (≤ or >3 cancer lesions).The primary endpoint was progression-free survival (PFS) as per iRECIST. Secondary endpoints included objective response rate (ORR), local control rate (LCR) and toxicity. Endpoints were assessed in the intention-to-treat population. Results Between March 2018 and October 2020 a total of 99 patients were randomized to either the control arm (n=52) or the experimental arm (n=47). Of those, 3 patients (control n=1 vs. experimental n=2) withdrew consent hence were not included in the analysis. More than 70% of patients had >3 tumor lesions at time of inclusion, other patient characteristics are represented in Table 1. Seven patients allocated to the experimental arm did not complete the study-prescribed SBRT course due to early disease progression (n=5) or intercurrent illness (n=2). With a median follow-up of 8.0 months (range 0.7-33.1) versus 11.2 months (range 0.7-35.0), respectively, median PFS was 2.8 months in the control arm as compared to 4.4 months in the experimental arm (p=0.7) (HR 0.91; 95% CI 0.55-1.49). ORR did not differ significantly between both arms (22 vs. 27%; p=0.5), despite a LCR of 77% in irradiated patients. Acute treatment-related toxicity of any grade and G3-4 occurred in 78.4% and 17.6% of patients in the control arm vs 77.8% and 17.8% in the experimental arm, respectively. No G5 adverse events occurred. The most common AEs included pruritus and fatigue.

Table 1. Baseline patient characteristics

Control arm (n=52) Experimental arm (n=47)

Primary tumor histology – no. (%) HNSCC Melanoma NSCLC RCC UC

11 (21) 12 (23) 4 (8) 8 (15) 17 (33)

9 (19) 11 (23) 3 (6) 6 (13) 18 (38)

Number of lesions – no. (%) ≤3 >3 AJCC stage – no. (%) III IV ICB regimen – no. (%) atezolizumab 3-weekly nivolumab 2-weekly nivolumab 4-weekly pembrolizumab 3-weekly

15 (29) 37 (71)

12 (26) 35 (74)

2 (4) 49 (93)

6 (13) 41 (88)

6 (12) 21 (40) 4 (8) 20 (38)

5 (11) 21 (45) 2 (4) 19 (40)

Number of SBRT-treated lesions – no. (%) 1 2 3

17 (36) 14 (30) 8 (17)

Figure 1. Progression-free survival