In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 9061-9061
Abstract:
9061 Background: To treat LCNEC with non-small cell lung carcinoma type chemotherapy (NSCLC-ct, i.e. gemcitabine/taxanes or pemetrexed) or small cell lung carcinoma type (SCLC-ct, i.e. platinum-etoposide) is subject of debate. Molecular studies have identified two mutually exclusive subtypes in LCNEC, the co-mutated TP53 and RB1and the STK11/ KEAP1 (predominantly RB1 wildtype( wt )) group. We investigated if overall survival (OS) and progression free survival (PFS) correlates with targeted next-generation sequencing (TNGS) results in LCNEC treated with NSCLC-ct or SCLC-ct. Methods: For this population based retrospective cohort study all diagnoses of stage IV ct treated high grade neuroendocrine carcinomas (NEC, not being SCLC) were retrieved from the Netherlands Cancer Registry and Pathology Registry (PALGA) (2003-2012). Panel-consensus pathology revision of original tumor slides was performed on (N = 230) and TNGS for genes TP53, RB1, STK11 and KEAP1 analyzed with a multi-sample variant caller (Needlestack). Results: LCNEC was consensus diagnosed in 146/230 and 77 passed quality control for TNGS. Mean coverage was 2832x, a mutation( mt ) in TP53 was present in 87%, RB1 mt in 46%, STK11 mt in 13% and KEAP1 mt in 18% of sequenced LCNEC. RB1 was co-altered with TP53 in 94% of LCNEC; mutually exclusive to STK11 mt (100%) but not KEAP1 mt (57%). NSCLC-ct or SCLC-ct was specified in 92% of patients and RB1 wt LCNEC treated with NSCLC-ct (n = 22) showed a trend to better OS compared to SCLC-ct (n = 13) (8.5 months (95% confidence interval (CI): [6.3-10.6]) vs. 5.8 [5.5-6.1] months, p = 0.055). Due to reported resistance in NECs we analyzed NSCLC-ct without pemetrexed-ct; OS was significantly longer for NSCLC-ct (n = 15) compared to SCLC-ct (9.6 [7.7-11.6] vs. 5.8 [5.5-6.1] months, p = 0.026). PFS of RB1 wt NSCLC-ct treated patients was significantly longer than SCLC-ct (p = 0.044), without pemetrexed (p = 0.018). In patients with RB1 mt LCNEC OS/PFS was not significantly different for NSCLC-ct vs. SCLC-ct. Conclusions: In LCNEC with RB1 wt , NSCLC-ct correlates with a more favorable outcome compared to SCLC-ct. However, RB1 mt LCNEC treated with NSCLC-ct do similarly worse as SCLC-ct. Prospective studies should be initiated.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.9061
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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