IPI score (derived neutrophil/(leukocytes minus neutrophils)ratio [dNLR]>3 plus LDH>upper limit normal) is a emerging tool to predict overall survival (OS) with ICIs in different tumor types. HPD has been reported in 15% of pts on ICIs using different criteria, including ours (PD at first restaging with ≥40% increase in sum of target lesions or ≥ 20% with appearance of multiple new lesions; Matos et al, ASCO 2018). We aimed to assess the prognostic value of IPI and the relevance of HPD in pts enrolled in Ph1T with TAs.
Retrospective analysis of a consecutive cohort of pts treated with experimental TAs at VHIO Ph1T Unit over the last 3 years (we excluded pts in the first dose escalation cohorts of each trial as well as TAs matched to validated biomarkers). Overall survival (OS) was correlated with VHIO HPD criteria and IPI.
In total, 180 pts were treated with TAs (34% FGFR, 26% PI3K, 19% MET, 13% NOTCH, 5% IDH, 3% RAF). In 39% of the cases, TAs were matched to an emerging enrichment molecular alteration. Median age 59y, 58% female, most common tumor types: 20% colorectal, 17% breast, 9% gynecological, 8% biliary tract. Best response was PD in 55%, SD in 41%, PR in 4%. Our HPD criteria was met in 10% of the cases, across all tumor types and targets (highest prevalence in colorectal pts treated with PI3K inhibitors, 5/18, 28%). Median progression-free survival was 1.8 months (m) [95% CI 1.7-2.2], not affected target selected, molecular match or IPI score (p > 0.2). Median OS was 7.9 m [6.7-10], significantly different as per IPI score (IPI0 18 m [7.8-NA]; IPI1 7.7 m [6.5-9.9]; IPI2 2.6 m [1.7-NA]; p < 0.001). Importantly, in pts with PD as best response while on TAs, HPD did not negatively affect OS (p = 0.43).
Our results show that a prognostic score developed in cohorts treated with ICIs also predicts long-term outcome with TAs in Ph1T. HPD criteria can be met with TAs treatment, but the lack of survival impact (different from internal and external cohorts exposed to ICIs) suggests that it is not a relevant clinical finding.
Clinical trial identification
Legal entity responsible for the study
Vall d´Hebron Institute Oncology.
Has not received any funding.
J. Tabernero: Advisory boards: Bayer, Boehringer Ingelheim, Genentech/Roche, Lilly, MSD, Merck Serono, Merrimack, Novartis, Peptomyc, Roche, Sanofi, Symphogen and Taiho. E. Garralda: Advisory role: Roche, NeoMed Therapeutics, Ellypses Pharma. All other authors have declared no conflicts of interest.