ItRECIST adapted efficacy assessment in solid tumors treated with intratumoral immunotherapy.
Authors: Oberoi Honey Kumar , Serres-Créixams Xavier , Alonso Guzman , Matos Ignacio , Hernando-Calvo Alberto , Muñoz-Couselo Eva , Diez Marc , Baraibar Iosune , Vieito Maria , Saavedra Santa Gadea Omar , Galvao Vladimir , Mur-Bonet Gemma , Cunill-Macià Guillem , Oliveira Mafalda , Felip Enriqueta , Macarulla Teresa , Elez Elena , Tabernero Josep , Brana Irene , Garralda Elena 
Published: June 2021

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Background: The development of human intratumoral therapy (HIT-IT) has surged as a promising strategy to overcome resistance to checkpoint inhibitors (CPI), promoting a stronger tumor-specific immune response while reducing systemic exposure. A broad variety of agents (i.e: oncolytic viruses, toll-like receptors agonists) administered both in superficial- and deep-seated lesions are being currently tested in clinical trials (CT). Due to the local intervention on tumors, radiological assessment by standard RECIST is challenging and new methods of response that capture and integrate the local and systemic response to HIT-IT are needed. We aimed to evaluate the feasibility and clinical utility of itRECIST (Goldmacher et al., 2020) in patients (pts) treated with HIT-IT in early phase CT. Methods: Retrospective analysis of a cohort of pts with different solid tumor types enrolled in CT including HIT-IT in our institution between August’18 and January’21. Clinical characteristics were collected. Efficacy in target-injected (T-I) and target-non-injected (T-NI) lesions was assessed by objective response rate (ORR) and disease control rate (DCR), as per itRECIST. Overall disease ORR and DCR were assessed per RECIST 1.1/iRECIST. Treatment-related adverse events (TRAEs) were assessed with CTCAE v.5.0. ORR was calculated with Clopper-Pearson method. Survival analysis was made using Kaplan-Meier method. Results: A total of 37 pts were included. Median age was 66 years, 19 pts (51%) were male, all pts had ECOG 0-1. 24 pts (65%) were CPI-naïve. Median previous lines of therapy was 2 (range [r]: 0-11). All pts (100%) received minimum 1 dose of HIT-IT. 6 pts (16%) were treated with monotherapy and 31 pts (84%) in combination with CPI. Median HIT-IT and CPI doses administered were 4 (r: 1-9) and 2 (r: 1-13), respectively. Injected lesions: cutaneous (16.2%), subcutaneous (21.6%), lymph node (32.4%), liver (29.7%). Median size of T-I lesions was 40 mm (r: 19-260). At data cutoff, 32 pts were evaluable. Median follow-up was 14.4 weeks (r: 1.0-81.1). Per RECIST 1.1, overall ORR was 6% (95% CI, 5-7) and DCR was 38% (95% CI, 21-56). Per itRECIST, ORR was 19% (95% CI, 7-36) and DCR was 63% (95% CI, 44-79) in T-I lesions (n = 32), and 10% (95% CI, 22-27) and 48% (95% CI, 29-67) in T-NI lesions (n = 29). Mean decrease in responding T-I and T-NI lesions was -47% (r: -21 to -100) and -41% (r: -26 to -59), respectively. No non-target (NT) lesion was injected. Median progression-free survival was 7.4 weeks (95% CI, 6.6 – 8.2). Median overall survival was 10.0 months (95% CI, 2.3 – 17.7). Incidence of TRAE was 58% (grade 1-2 IT-related pyrexia 43%; grade 3-4, 5%). No treatment-related deaths were recorded. Conclusions: ItRECIST is feasible to implement and adds precision to the radiological assessment of local and distant anti-tumor activity of HIT-IT. No safety issues were detected in our cohort.