To improve patient selection is crucial issue in phase 1 trial. Many prognostic factors and scoring systems such as the Royal Marsden Hospital score which includes serum albumin, LDH, and number of metastatic sites have been reported. However, it is unclear whether these factors could adapt to phase 1 trials of immunocheck point inhibitor because of the specific features and clinical course of immunotherapy. Therefore, we investigated the factors that have affected survival in oncology phase 1 trials of immunocheckpoint inhibitors.
We retrospectively evaluated 65 phase 1 trials at our institution conducted between June 2009 and November 2016 from our database. Patients who received immunocheck point inhibitors for advanced solid tumor were eligible. Some121 patients enrolled in 11 trials were eligible. Outcome and factors affecting survival were investigated.
Eighty two events (67.8%) occurred. Median survival time (MST) of overall population from the day of administration of the investigational drugs was 12.8 months (95% confidence interval [CI]: 9.5-13.1). In univariate analysis, serum albumin ≺ 3.5g/dl, lactate dehydrogenase > normal upper limit, > 2 sites of metastasis, male, hemoglobin > 10.5 g/dl, neutrophil to lymphocyte ratio > 3 were significant poor prognostic factors. In multivariate analysis, serum albumin (hazard ratio [HR] 2.01 95% CI: 1.06-3.66), lactate dehydrogenase (HR 2.26 95%CI: 1.38-3.68), > 2 sites of metastasis (HR 3.86 95%CI: 2.31-6.44) and male (HR 2.22 95%CI: 1.30-3.86) were poor prognostic factors of overall survival.
In our study, the prognostic factors of overall survival in phase 1 trials of immunocheck point inhibitors were revealed similar features and were consistent with classical prognostic factors.Legal entity responsible for the study
National Cancer Center Hospital
Clinical trial identification
Legal entity responsible for the study
National Cancer Center Hospital
T. Shimizu: Reserch fund Bristol-Myers Squibb FivePrime PharmaMar honoreria ONO Pharmaceutical Co. Ltd. ONO Pharma Taiwan Co.Ltd. Chugai Pharmaceutical Co. Ltd. S. Kitano: Paid consultant for a company or supplier Ono. Daiichi-Sankyo. Astra Zeneca. Merek (MSD), Chugai, Eizai, Kyowa Kirin). Unpaid consultant for a company or supplier Boehringer Ingelheim,Ohtsuka, Merck Serono, Novaltis, Research support from a company or supplier Astellas, Gilead, Eizai, Regeneron Board member/committee appointments for a society Japanese Society of Medical Oncology,Japanese Association of Cancer Immunology, Japan Society for Biological Therapy, Japan Society of Urologic Oncology, Japanese Society of Renal Cancer, Y. Fujiwara: Grants/Research Support Recipient: AstraZeneca, BMS, Chugai, Daiichi-Sankyo, Eisai, Incyte, MerckSerono, MSD Speaker’s Bureau: BMS, ONO, Taiho, Boehringer Ingelheim, All other authors have declared no conflicts of interest. K. Yonemori: Lecture\'s fee Taiho, Eisai, Mochida, Novartis Grant Novartis. S. Iwasa: Research Grant: Bristol-Myers Squibb, Merck Serono, Chugai, Novartis, Lilly, Daiichi-Sankyo. Leuture\'s fee: Lilly. N. Yamamoto: Research grants: Quintiles, Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO. Advisory role: Eisai, Takeda, Onco Therapy Science. Speakers: BMS, Pfizer, AstraZeneca, Eli Lilly, ONO, Chugai