期刊
EUROPEAN JOURNAL OF CANCER
卷 148, 期 -, 页码 215-229出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2021.01.050
关键词
STK11; Immunotherapy; Non-small cell lung cancer; KRAS; Cancer
类别
资金
- National Cancer Institute [P30 CA023100]
- Joan and Irwin Jacobs Fund philanthropic fund
The study revealed that mutations in the STK11 gene are closely associated with the malignancy and survival rates of tumors, especially when co-altered with KRAS. Patients with co-alterations of STK11 and KRAS in the pan-cancer setting had worse outcomes regardless of treatment type.
Background: STK11 is an important tumour suppressor gene reported to confer immunotherapy resistance in non-small-cell lung cancers (NSCLC) especially in the presence of KRAS co-alterations Methods: This study analysed 4446 patients for whom next-generation sequencing of tissue and/or circulating tumour DNA (ctDNA) had been performed. Results: Overall, 60 of 4446 tumours (1.35%) harboured STK11 alterations. STK11 alterations were associated with shorter median time to progression and overall survival (OS) across cancers from diagnosis: 6.4 months (5.1-7.9) versus 12 months (11.7-12.3; p = 0.001); and 20.5 (17.4-23.5) versus 29.1 (26.9-31.3; p = 0.03), respectively (pan-cancer). Pan-cancers, the me-dian progression-free survival (PFS; 95% CI) for first-line therapy (regardless of treatment type) for those with co-altered STK11 and KRAS (N = 27; versus STK11-altered and KRAS wild type [N = 33]), was significantly shorter (3 [1.3-4.7] versus 10 [4.9-15.7] months, p < 0.0005, p multivariate, 0.06); the median OS also was also shorter (p multivariate = 0.02). In pan-cancer patients treated with checkpoint blockade, STK11 and KRAS co-altered versus STK11-altered/KRAS wild type had a shorter median PFS and trend toward shorter OS (p = 0.04 and p = 0.06, respectively). In contrast, in examining STK11- altered versus wild-type pan-cancer patients treated with checkpoint blockade immuno-therapy, the two groups showed no difference in outcome (PFS [p = 0.4]; OS [p = 0.7]); STK11-altered versus wild-type lung cancer patients also did not fare worse on immunotherapy. Conclusions: Across cancers, STK11 alterations correlated with a poor prognosis regardless of therapy. However, STK11 alterations alone did not associate with inferior immunotherapy outcome in the pan-cancer setting or in NSCLC. Pan-cancer patients with co-altered STK11/KRAS did worse, regardless of treatment type. (C) 2021 Elsevier Ltd. All rights reserved.
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