In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21536-e21536
Abstract:
e21536 Background: The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti-programmed cell death-ligand 1 (PD-L1) drug therapy. BIM deletion induces apoptosis suppression and the effect of epidermal growth factor-tyrosine kinase inhibitor is reportedly attenuated in EGFR-mutated NSCLC patients with BIM deletion. This study retrospectively examined the effects of BIM deletion on CRT or PD-1 treatment in patients with NSCLC. Methods: Among patients with unresectable NSCLC at Higashi-Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and April 2018, we enrolled those treated with CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or PD-1 antibody treatment. Results: Of 1,224 patients with unresectable NSCLC, 88, 80, and 79 underwent CRT, chemotherapy, or PD-1 antibody treatments, respectively. Within these treatment groups, 15 (17%), 15 (19%) and 11 (14%) patients, respectively, had BIM deletion. Among patients receiving CRT, the progression-free survival and overall survival were significantly shorter in those with BIM deletion than in those without (150 vs. 254 days, p = 0.003; 429 vs. 710 days, p = 0.03). Moreover, multivariate Cox regression analysis showed BIM deletion to be an independent factor for anti-tumor effect or prognosis (hazard ratio [95% confidence interval] 2.042, [1.112–4.039], p = 0.029; 2.414, [1.063–4.984] , p = 0.036). These results were not observed in the chemotherapy and PD-1 treatment groups. To confirm the association between radiation therapy effect and BIM deletion, we performed in vitro experiments using two NSCLC cell lines (A549 and EBC-1). Suppressed BIM expression using siRNA (instead of BIM deletion) in these cells showed significantly suppressed antitumor effect and apoptosis 48 hours after 30-Gy irradiation but not chemotherapy. Conclusions: We showed that BIM deletion is an independent anti-tumor effect or prognostic factor for CRT. The results also indicated that BIM deletion was associated with the effects of radiation but not chemotherapy or PD-1 antibody treatment.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e21536
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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