Ullas Batra1, Mansi Sharma2, Shrinidhi Nathany3, Abhishek Bansal4, Sunil Pasricha5, Parveen Jain2, Anurag Mehta6, Harkirat Singh2. 1. Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India. ullasbatra@gmail.com. 2. Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India. 3. Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India. 4. Radiology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India. 5. Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India. 6. Laboratory Services, Molecular Diagnostics and Transfusion Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India.
Abstract
INTRODUCTION: EGFR (epidermal growth factor receptor) mutant NSCLC (non-small cell lung carcinoma) comprises 35-40% of cases in the Asian NSCLC cohort, compared to 15-20% in the rest of the world. Improved response rates have been observed in terms of PFS (progression-free survival) and ORR (overall response rate) when treated with EGFR TKIs (tyrosine kinase inhibitors). However, resistance eventually ensues regardless of the generation of TKI used. Preclinical studies have reported that PDL1 (programmed death ligand 1) is a downstream target of EGFR and is interposed by IL-6/JAK/STAT3 (interleukin-6/Janus kinase/signal transducer and activator of transcription 3), NF-κB (nuclear factor kappa beta), and p-ERK1/2/p-c-Jun pathways. Hence, it may potentially be repressed by EGFR TKIs. In this retrospective exploratory analysis, we studied whether PDL1 expression affects efficacy of EGFR TKIs and clinical outcome in patients with untreated metastatic EGFR-mutated lung adenocarcinoma. METHODS: This single-center retrospective, exploratory analysis was performed between January 2015 and December 2019. Among 1350 cases of NSCLC, 470 were EGFR mutant, of which PDL1 expression testing was done in 193 patients who were included in this study. RESULTS: Median age was 60 years (range 24-87 years). A total of 116 patients (60.1%) had inframe deletion in exon 19, 52 (26.9%) had L858R, and 25 (13%) had uncommon mutations. The number of patients with PDL1 tumour proportion score (TPS) < 1% was 109 (56.5%); 1-49%, 57 (29.5%); and ≥ 50%, 27 (14%). Comparing clinical characteristics among various PDL1 groups, there were no statistically significant correlations obtained. However, patients with PDL1 > 50% were smokers, and showed a trend for higher disease burden at diagnosis. Median PFS of PDL1 < 1% was 10.14 months, compared to 9.4 months in the PDL1 > 1% group; however, the values did not reach statistical significance. CONCLUSION: The current study was an exploratory retrospective study; however, the results add to the growing body of evidence that PDL1 expression in EGFR-mutated NSCLC does not have any prognostic significance. Also the efficacy of EGFR TKIs is not influenced by variations in PDL1 TPS.
INTRODUCTION: EGFR (epidermal growth factor receptor) mutant NSCLC (non-small cell lung carcinoma) comprises 35-40% of cases in the Asian NSCLC cohort, compared to 15-20% in the rest of the world. Improved response rates have been observed in terms of PFS (progression-free survival) and ORR (overall response rate) when treated with EGFR TKIs (tyrosine kinase inhibitors). However, resistance eventually ensues regardless of the generation of TKI used. Preclinical studies have reported that PDL1 (programmed death ligand 1) is a downstream target of EGFR and is interposed by IL-6/JAK/STAT3 (interleukin-6/Janus kinase/signal transducer and activator of transcription 3), NF-κB (nuclear factor kappa beta), and p-ERK1/2/p-c-Jun pathways. Hence, it may potentially be repressed by EGFR TKIs. In this retrospective exploratory analysis, we studied whether PDL1 expression affects efficacy of EGFR TKIs and clinical outcome in patients with untreated metastatic EGFR-mutated lung adenocarcinoma. METHODS: This single-center retrospective, exploratory analysis was performed between January 2015 and December 2019. Among 1350 cases of NSCLC, 470 were EGFR mutant, of which PDL1 expression testing was done in 193 patients who were included in this study. RESULTS: Median age was 60 years (range 24-87 years). A total of 116 patients (60.1%) had inframe deletion in exon 19, 52 (26.9%) had L858R, and 25 (13%) had uncommon mutations. The number of patients with PDL1 tumour proportion score (TPS) < 1% was 109 (56.5%); 1-49%, 57 (29.5%); and ≥ 50%, 27 (14%). Comparing clinical characteristics among various PDL1 groups, there were no statistically significant correlations obtained. However, patients with PDL1 > 50% were smokers, and showed a trend for higher disease burden at diagnosis. Median PFS of PDL1 < 1% was 10.14 months, compared to 9.4 months in the PDL1 > 1% group; however, the values did not reach statistical significance. CONCLUSION: The current study was an exploratory retrospective study; however, the results add to the growing body of evidence that PDL1 expression in EGFR-mutated NSCLC does not have any prognostic significance. Also the efficacy of EGFR TKIs is not influenced by variations in PDL1 TPS.
Authors: K Azuma; K Ota; A Kawahara; S Hattori; E Iwama; T Harada; K Matsumoto; K Takayama; S Takamori; M Kage; T Hoshino; Y Nakanishi; I Okamoto Journal: Ann Oncol Date: 2014-07-09 Impact factor: 32.976
Authors: Helen Brown; Johan Vansteenkiste; Kazuhiko Nakagawa; Manuel Cobo; Thomas John; Craig Barker; Alexander Kohlmann; Alexander Todd; Matilde Saggese; Juliann Chmielecki; Aleksandra Markovets; Marietta Scott; Suresh S Ramalingam Journal: J Thorac Oncol Date: 2019-10-09 Impact factor: 15.609