Tumor growth rate as an early indicator of the efficacy of anti-PD-1 immunotherapy in advanced melanoma.

Abstract

e21050 Background: As immunotherapeutics take longer time to show clinical efficacy compared with chemotherapy and targeted therapy, it is critical to select patients with low tumor growth rate (TGR) prior immunotherapy as to get sufficient time for immunotherapeutics to play functions. However, which threshold of TGR before immunotherapy may be associated with good outcome remains unknown. Methods: Medical records from patients with advanced refractory melanoma prospectively treated in clinical trials (NCT02836795 and NCT03013101) of anti-PD-1 antibody toripalimab were analyzed. TGR was computed during the pretreatment period (reference) and the treatment period (treatment). Associations between TGR and objective response at the first evaluation, progression free survival (PFS), overall survival (OS) were computed. Results: We analyzed a total of 142 patients enrolled in these two clinical trials. Excluded for no measurable lesions in pretreatment period or incomplete imaging data through the pretreatment/treatment periods, a total of 90 patients could be explored for the relationship of TGR and the efficacy of anti-PD-1 antibody. TGR and hyperprogression were defined as Champiat S. used to make. The distribution of TGR is as follows: median 63.7 (range: -51~720). A total of 15 (16.7%), 41 (45.6%), 34 (37.8%) and 0 patients exhibited PR, SD, PD, CR, respectively. An association between lower TGR (TGR ≤55) and objective response was observed (P≤0.001). Among evaluable patients at week 8, 83.9% (13+34/56) and 26.5% (2+7/34) showed PR/SD from baseline tumor measurements for the group of TGR≤55 and TGR > 55, respectively. Median PFS was 5.5 0.9m in the group of TGR≤55 compared 1.8 0.4m in the group of TGR > 55 (P≤0.001). Median OS was not reached in the group of TGR≤55 group and was 15.9 1.8m in the group of TGR > 55 (p = 0·02). Two patients were confirmed pseudoprogression in the follow-up. The TGR of these two patients was lower than 55. Five patients experienced hyperprogression. The TGR of each patient was 9, 12, 54, 56, 78, respectively. Conclusions: Melanoma patients with TGR≤55 prior anti-PD-1 antibody therapy are more likely to benefit from this regimen. However, it could not predict patients who may develop hyperprogression after anti-PD-1 antibody therapy. Clinical trial information: NCT02836795 and NCT03013101.