Lymphocytes and neutrophils count after two cycles and TTF1 expression as early outcome predictors during immunotherapy (IT) in stage IV non-small cell lung cancer (NSCLC) patients.

Abstract

e20553 Background: NSCLC therapeutic paradigm has changed with immune checkpoint blockers. Biomarkers predicting clinical benefit are still lacking. As previously shown in melanoma, changes in absolute lymphocytes and neutrophils count (ALC and ANC) during IT (PD-1/PD-L1 inhibitors) may be related to response in NSCLC (Nakamuta et al, Oncotarget 2016). TTF1 expression has been associated with PD-L1 expression (Vieira et al, Lung Cancer 2016). We aimed to investigate TTF1 expression and changes in ALC and ANC after 2 cycles and their potential association with clinical outcomes to IT. Methods: We retrospectively analyzed 26 consecutive patients with stage IV NSCLC treated with IT at Clínica Universidad de Navarra (Spain) during 2016. Radiological response was evaluated according to RECIST v1.1. The potential correlation between ALC and ANC changes during the first two cycles and response to treatment [disease control rate (DCR) vs progression] was evaluated using Student’s T-test. Fisher’s exact test was used to study the association between changes in ALC ( < 1,000 vs > 1,000) and ANC ( < 4,000 vs > 4,000) after 2 cycles and response to IT. TTF-1 expression was correlated with treatment response. Overall survival (OS) was assessed with Kaplan-Meier analysis and Log-rank test according to ALC and ANC. Results: An ALC increase after 2 cycles was significantly associated with DCR compared to progression (192 vs -155; p = 0.043). ALC > 1,000 after 2 cycles was more frequent among patients experiencing DCR compared to progression (87% vs 50%; p = 0.07). ALC > 1,000 after 2 cycles was more frequently observed among patients with TTF1+ tumors (93% vs 55%; p = 0.03). Patients with ANC < 4,000 showed a longer median OS (NR vs 19.25 months; p = 0.03). TTF1 expression in adenocarcinoma (n = 18) was associated with response to IT (83% vs 16%, p = 0.01). Conclusions: Despite this retrospective small series’ limitations, our results show that ALC and ANC changes during IT and TTF1 expression may act as early predictors of clinical benefit in stage IV NSCLC patients treated with PD1/PD-L1 blockers. Our results warrant further investigation in larger prospective series.

Differential Expression of PD-L1 in Central and Peripheral and TTF1-Positive and -Negative Small-Cell Lung Cancer

“…The positive association between PD-L1 and TTF-1 expression has been reported in pulmonary sarcomatoid carcinomas ( 33 ). Furthermore, TTF-1 expression was shown to predict the response to immune checkpoint inhibitors in NSCLC ( 34 ). So it can be speculated that high TTF-1 expression could be a predictive marker for anti-PD-1/PD-L1 therapy in SCLC.…”

Durable complete response to immunotherapy in treatment‐resistant metastatic colorectal cancer with thyroid transcription factor 1 expression

“…TTF‐1 expression has most frequently been associated with microsatellite stability rather than MSI‐H CRCs 6. Of greatest interest, in patients with lung adenocarcinoma, TTF‐1 expression has been associated with increased PDL1 expression, dramatic responses to ICI therapy (83% versus 16%) and improved survival 9. Consequently, TTF‐1 may be an important predictive biomarker of ICI response in mCRC and warrants further investigation in this regard.…”