Abstract 1835P
Background
Overall survival (OS) of phase 1 (P1) cancer patients (pts) is difficult to predict. The Royal Marsden Hospital (RMH) prognostic score (which incorporates serum albumin, LDH, and no. of metastatic sites) and neutrophil-lymphocyte ratio (NLR) have been validated to predict OS in P1 trial pts in the Western population but not Asian pts. It is also important to validate the RMH score and NLR for newer phase I studies, including immunotherapy and vaccine studies. This study aims to validate the RMH score and NLR in a P1 clinical trials unit in Singapore and is the largest Asian study to date which includes novel P1 therapies.
Methods
We conducted a retrospective review of pts in P1 studies between Oct. 2013 – Nov. 2020 at the National University Cancer Institute, Singapore with electronic medical records available. Pt characteristics and survival data were analyzed. A Cox model was used to identify independent predictors of OS assuming two-sided 5% level of significance.
Results
We analyzed 414 pts treated in 42 P1 studies. Pt characteristics were as follows: age >60 (51%), male (37.9%), ECOG 0 vs 1-2 (47.3% vs 52.7%), comorbidities ≥2 (19.1%), prior therapies ≥3 (47.1%, range: 0-13), no. of metastatic sites ≥3 (45%), immunotherapy (17.9%), and vaccine studies (4.3%). The table shows the multivariable analysis of OS. Median OS duration with NLR <3, 3-9 and >9 were 15.1, 8.9 and 5 months, respectively. Pts with higher RMH score had a significantly shorter median OS duration as compared with RMH score 0 (Score 2: 8.2 vs. 16.4 mo, HR: 2.28, 95% CI: 1.64 – 3.18, p<0.001; Score 3: 3.2 vs. 16.4 mo, HR: 4.05, 95% CI: 2.6 – 6.3, p<0.001). Adjusting for ECOG performance status, tumor type and NLR, the RMH prognostic score remained an independent prognostic factor for OS (RMH 2-3 compared to 0-1, HR = 1.85; 95% CI= 1.39-2.49). However, the ROC area under curve declines as time progresses. Table: 1835P
| Characteristics | HR (95% CI) | p-value |
| Albumin ≥35 vs. <35 g/L | 1.66 (1.23 – 2.24) | < 0.001 |
| LDH ≤580 vs. >580 IU/L | 1.37 (1.06 – 1.79) | 0.018 |
| No.of metastatic sites 0-2 vs. ≥3 | 1.47 (1.15 – 1.87) | 0.002 |
| ECOG performance status 0 vs. 1-2 | 1.62 (1.26 – 2.08) | <0.001 |
| Tumor type: Breast GI Other | Ref 2.82 (1.99 – 3.99) 1.70 (1.24 – 2.33) | < 0.001 < 0.001 |
| NLR <3 NLR 3-9 NLR > 9 | Ref 1.50 (1.17 – 1.92) 2.15 (1.43 – 3.24) | <0.001 <0.001 |
Conclusions
RMH score and NLR both remain significant predictors of OS and are useful for patient selection for phase I studies in Asian pts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.