Selecting the appropriate pts to receive IO remains a challenge due to the lack of optimal biomarkers. We investigated the association between sites of metastatic disease and CO in pts enrolled on IO-based phase 1 clinical trials.
We conducted a retrospective review of 90 pts treated on IO-based phase 1 clinical trials at Winship Cancer Institute of Emory University between 2009-2017, including sites of metastasis. Overall survival (OS) and progression-free survival (PFS) were measured from the first dose of IO to date of death or clinical or radiographic progression, respectively. Clinical benefit (CB) was defined as a complete response (CR), partial response (PR), or stable disease (SD). Univariate analysis (UVA) and multivariate analysis (MVA) was carried out using Cox proportional hazard model or logistic regression model.
The median age was 63 years and 53% of pts were men. The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). Sites of metastasis were lymph node (N = 58), liver (N = 40), lung (N = 37), bone (N = 24), and brain (N = 8). Most pts (81%) were Royal Marsden Hospital (RMH) good risk. Liver metastases were associated with significantly shorter OS, PFS, and lower rate of CB (Table).Table: 1221P
UVA and MVA† of liver metastases with CO
|HR (CI)||p-value||HR (CI)||p-value||HR (CI)||p-value||HR (CI)||p-value||OR (CI)||p-value||OR (CI)||p-value|
|No liver metastases (n = 50)||0.42 (0.23-0.78)||0.006*||0.38 (0.17-0.84)||0.017*||0.60 (0.39-0.93)||0.024*||0.73 (0.42-1.26)||0.255||2.64 (1.11-6.28)||0.028*||1.09 (0.27-4.44)||0.903|
|Median: 21.9 months 12 month survival: 60%||Median: 3.6 months 12 month survival: 13%||Rate: 56% (6 PR, 22 SD, 17 PD, 5 NE)|
|Liver metastases (n = 40)||Median: 8.1 months 12 month survival: 19%||Median: 1.8 mos 12 month survival: 5%||Rate: 33% (1 CR, 1 PR, 11 SD, 24 PD, 3 NE)|
Covariates included in MVA were age, whether IO is indicated for the pts histology, ECOG PS, RMH risk group, number of metastatic sites and histology*
statistically significant PD: Progressive disease, NE: Not evaluable
Liver metastases are a poor prognostic factor in pts treated on IO-based phase 1 clinical trials. These findings should be validated in a larger study. Equal Contribution: MAB, JMS, DJM.
Clinical trial identification
Legal entity responsible for the study
Emory University IRB.
Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of the Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
M.A. Bilen: Consulting/advisory role: Exelixis, Sanofi; Research funding: Bayer, Bristol-Myers Squibb, Genentech/Roche, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Peleton, Pfizer. B.C. Carthon: Consulting/advisory role: Astellas Medivation, Pfizer, Blue Earth Diagnostics; Travel accommodations: Bristol-Myers Squibb. W.L. Shaib: Research funding: ArQule, Lilly. C. Wu: Honorarium: BioTheranostics; Research funding: Amgen, Bristol-Myers Squibb, Vaccinex, Boston Biomedical. R. Kudchadkar: Consulting/advisory role: Bristol-Myers Squibb, Novartis, Array BioPharma; Honorarium: Bristol-Myers Squibb; Research funding: Merck. B. El-Rayes: Consulting/advisory role: Merrimack, BTG, Bayer, Loxo, RTI Health Solutions; Member of the speakers’ bureau: Lexicon, Bristol-Myers Squibb; Honorarium: from Lexicon, RTI Health Solutions, Bayer; Research funding: Taiho Pharmaceutical, Bristol-Myers Squibb, Boston Biomedical, Cleave Biosciences, Genentech, AVEO, Pfizer, Novartis, Hoosier Cancer Research Network, Five Prime Therapeutics, PPD Inc., Merck, ICON Clinical research. S.S. Ramalingam: Consulting/advisory role: Amgen, Boehringer Ingelheim, Celgene, Genetech/Roche, Lilly/ImClone, Bristol-Myers Squibb, AstraZeneca, Abbvie, Merck, Takeda; Travel accommodations: EMD Serono, Pfizer, AstraZeneca. T.K. Owonikoko: Consulting/advisory role: Novartis, Celgene, Lilly, Sandoz, Abbvie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol-Myers Squibb, MedImmune; Intellectual property of the following: “Overcoming acquired resistance to chemotherapy treatments through suppression of STAT3” and “Selective chemotherapy treatments and diagnostic methods related thereto”; Research funding: Novartis, Astellas Pharma, Celgene, Bayer, Stem CentRx, Regeneron, AstraZeneca/MedImmune, Abbvie, G1 Therapeutics, and Bristol-Myers Squibb. All other authors have declared no conflicts of interest.