Phase I clinical trials are an essential step for the development of new anticancer treatments. Next-generation phase I trials investigating novel drugs led to consistent improvements in terms of response rates and survival of the enrolled pts. The aim of our study is to evaluate the outcomes of patients enrolled in phase I trials testing targeted therapies (TT), immunotherapy (IT), and combinations.
We retrospectively reviewed clinical characteristics and outcomes of all consecutive pts with advanced/metastatic cancers who were screened and/or treated at our Early Drug Development Unit between Dec 2014 and Nov 2018. Factors associated with ORR and CBR were tested with logistic regression in univariate and multivariate analyses. Primary objectives of the study were to determine overall response rate (ORR) and disease control rate (DCR), according to RECIST 1.1 or iRECIST criteria. Factors associated with ORR and CBR were tested with logistic regression in univariate and multivariate analyses. Statistical significance threshold was set to a two-tailed 0.05 value.
723 pts were screened. Median age was 57 years (22-82). After study screening procedures, 481 pts (66.5%) resulted as not-eligible, mainly due to the absence of druggable molecular alteration(s) for biomarker-driven trials (56.1%), abnormal lab tests (12.7%), or poor performance status (11.4%). Conversely, the 242 (33.5%) eligible pts received IT (47.5%), TT (48.3%), or combinations (4.2%). Most common tumor types were breast, lung, gynecological, and gastrointestinal cancers (43.6%, 13.6%, 9.3%, 7.6%, respectively). ORR and CBR were 14.8% and 28.0%, respectively. Pts with less than 2 metastatic sites had a higher CBR (35% vs 17%; OR 2.67; 95% CI, 1.39-5.10; p=0.003), while pts who received less than 2 prior lines of systemic therapy presented higher ORR (18% vs 10%; OR 2.37; 95%, CI 1.03-5.44; p=0.004).
Our analysis confirms substantial improvements in terms of outcomes in next-generation phase I trials. Heavily pre-treated pts as well as those with higher burden of disease have worse outcomes, underlining that pts should be enrolled in earlier lines of therapy to maximize the clinical benefit.
Istituto Europeo di Oncologia IRCCS.
Has not received any funding.
G. Curigliano: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche, Pfizer, Novartis, Seattle Genetics, Lilly, Ellipses Pharma, Foundation Medicine and Samsung. All other authors have declared no conflicts of interest.