Immune checkpoint blockers (ICB) in combination with antiangiogenic drugs showed synergistic efficacy in several tumor types. New patterns of progression have recently been defined upon treatment with ICB alone including atypical responses such as pseudoprogression (PsPD), dissociated response (DisR). This study aimed at describing patterns of progression observed with patients treated with combination ICB with antiangiogenic drugs.
We conducted a monocentric retrospective analysis of patients (pts) enrolled in phase I trials at Gustave Roussy evaluating the combination of ICB and antiangiogenic drugs. Radiological CT scans were centrally reviewed by a radiologist senior according to iRECIST criteria including progressive disease (PD), partial response (PR) and stable disease (SD). HPD was defined as a progression at the first evaluation with delta tumor growth rate exceeding 50%. PsPD was defined as initial progression followed by stabilization or decrease of tumor size, DisR as a concomitant size decrease in some tumor lesions and size increase in others. Both PsPD and DisR are defined as atypical responses. Overall response rate (ORR) included partial response (PR) and complete response (CR) and disease control rate (DCR) included PR, CR and stable disease.
Between December 2016 and June 2020, 111 pts were included in the analysis, the most common tumor types were pleura (20%), kidney (18%) and bladder (17%). The ORR and DCR were 23% (n=24) and 59% (n=65), respectively. Twenty-one patients (19%) experienced progressive disease (PD) as the best response. PsPD, DisR and HPD were observed in 7 (6%), 11 (10%) and 7 (6%) pts, respectively. DisR and PsPD were associated with longer PFS (median PFS: 6.9 and 18.9 months, respectively, p>0.05 NS) and OS (median OS: 28.4 and 31.1 months, respectively, p>0.05 NS) compared with SD (PFS=4.17 months, OS=12.7 months).
Patients treated with ICBs and antiangiogenic agents display atypical responses. Survival may be longer in patients with DisR responses and PsPD disease when compared to HPD, PD and SD patients.
Legal entity responsible for the study
Gustave Roussy, Villejuif.
Has not received any funding.
All authors have declared no conflicts of interest.