P1.04-56 Landscape of Tumor Mutational Burden in Indian NSCLC Patients

Abstract

Background: Following to approval of Pembrolizumab for patients with advanced NSCLC, PD-L1 IHC 22C3 pharmDx (Dako) was adopted as a companion diagnostic test. While PD-L1 IHC 28-8 pharmDx (Dako) was established as a complementary diagnostic for Nivolumab. Recently many groups demonstrated the intra-tumor heterogeneity of these PD-L1 expressions, but there have been a few reports about the intra-patient or inter-tumor heterogeneity. We aimed to investigate the inter-tumor heterogeneity of PD-L1 IHC 22C3 and 28-8 pharmDx (Dako). Method: Between December 1, 2014 and May 7, 2018, total 517 patients with NSCLC underwent surgical resection at our hospital. We excluded all patients with no informed consent, with no lymph node metastasis, with chemotherapy/radiotherapy before surgery and with never enough volume of material for genetic testing. Finally, 35 formalin-fixed paraffin-embedded primary tumors with paired metastatic lymph nodes were available in this study. After staining by PD-L1 IHC 22C3 and 28-8 pharmDx (Dako) respectively, we counted tumor cells exhibiting membrane staining and calculated Tumor Proportion Score (TPS). Afterward, all cases were classified into three subgroups as follows; No Expression (TPS: <1%), Low Expression (TPS: 1-49%) and High Expression (TPS: 50%). Result: Average age of 35 patients was 66.8 years old and there were 10 females (28.6%), 10 never smokers (28.6%), 27 adenocarcinomas (77.1%) and 11 tumors with EGFR mutation. The number of cases in No Expression, Low Expression and High Expression in 22C3 were 7 (20.0%), 22 (62.8%) and 6 (17.1%) in primary tumor, meanwhile 18 (51.4%), 13 (37.1%) and 4 (11.4%) in metastatic lymph node, respectively. The concordant rate was 28.6% between TPS subgroups in primary tumor and that in metastatic lymph node. About 28-8 antibody, No Expression, Low Expression and High Expression were 8 (22.9%), 21 (60.0%) and 6 (17.1%) in primary tumor, meanwhile 18 (51.4%), 11 (31.4%) and 6 (17.1%) in metastatic lymph node, respectively. The concordant rate was 31.4% between TPS subgroups in primary tumor and that in metastatic lymph node. Conclusion: Our result demonstrated apparent discrepancy of TPS between primary tumor and metastatic lymph node in both PD-L1 IHC 22C3 and 28-8.

Impact of the STK11/KRAS co-mutation on the response to immunotherapy in a real-world pan-cancer cohort

“…19 It was shown to worsen the treatment outcome in patients receiving both chemotherapy and ICI, though prognostic significance is less pronounced in the cohort of patients receiving ICI. 6,16,20,21 Consequently, STK11 may play both a prognostic and predictive role, which agrees with our results. Since STK11 mutations are frequently observed in PD-L1-low/TMB-low patients 22,23 this marker may provide an additional molecular-defined cohort of patients with NSCLC, which may benefit more from immunotherapy.…”

“…5 The high mutational burden correlates with the immunogenic microenvironment of the tumor and the increased expression of tumor-specific neoantigens, which can become a target for activated immune cells. 6 Evidence suggests alterations in frequently mutated genes (KRAS, TP53, STK11, KMT2C, LRP1B, POLE and others) as drivers of response or resistance to ICI treatment. Somatic mutations in serine/threonine kinase 11 (STK11) have been proposed as a prognostic marker that correlates with poor treatment outcome in non-small cell lung cancer (NSCLC).…”

“…5 The high mutational burden correlates with the immunogenic microenvironment of the tumor and the increased expression of tumor-specific neoantigens, which can become a target for activated immune cells. 6…”