Dynamics of neutrophil to lymphocyte ratio (NLR) predict effectiveness of PD1/PDL1 inhibition

Background

Baseline neutrophil/lymphocyte ratio (NLR) has repeatedly been associated with progression free (PFS) and overall survival (OS) of patients with advanced cancer. We explored whether changes in NLR can predict PFS of advanced cancer patients (pts) enrolled into Phase-1 (Ph-1) trials and treated with anti-PD1/PDL1 inhibitors.

Methods

Stage IV cancer patients enrolled into Ph-1 trials between September 2013 and May 2016, and treated with an anti-PD1/PDL1 checkpoint inhibitors were included in this study. NLR was calculated at baseline, before starting treatment (cycle 1 day 1), and after 2 cycles (cycle 3 day 1) of treatment. Royal Marsden Prognostic Score (RMPS) was calculated at baseline for all patients enrolled. Kaplan-Meier estimation and Cox regression analyses with a random effect for tumour entity (to account for heterogeneity between tumour types) were used to assess the impact of NLR changes on PFS. Pts who were not able to receive at least 2 cycles of treatment were excluded to avoid guarantee time bias.

Results

Of 67 pts treated, 12 were excluded because not receiving 2 full cycles of anti-PD1/PDL1 treatment. In total 55 pts were eligible (median age of 61 years, PS 0/1 = 65.5% / 34.5%, female = 34.5%). Tumour types were non-small cell lung cancers (n = 18, 32.7%), renal cell (n = 8, 14.5%), upper gastrointestinal (n = 10, 18.2%), breast (n = 7, 12.7%), urothelial (n = 8, 14.5%), colorectal (n = 2, 3.6%), ovarian (n = 1, 1.8%), and small bowel cancers (n = 1, 1.8%). Before trial enrolment pts received a median of 1 treatment line (range 1-6), and presented with a median number of 2 metastatic sites (range 0-4). 24 (43.6%) patients had a RMPS of 1 or higher. 26 (47.3%) patients received an anti-PDL1 monoclonal antibody (MAb) and 29 (52.7%) an anti-PD1 MAb. Patients with increasing NLR between baseline and 2 cycles had a significantly shorter PFS in univariate analysis (HR 1.63, 95% CI 1.27 – 2.11, p 

Conclusions

Changes in the NLR (as continuous variable) after 2 cycles of treatment with anti-PD1/PDL1 treatment independently predict PFS in patients with multiple types of advanced cancer.

Clinical trial identification

Legal entity responsible for the study

Sarah Cannon Research Institute UK

Funding

Sarah Cannon Research Institute UK

Disclosure

All authors have declared no conflicts of interest.