Highlights
- •STK11 alterations had shorter median time to progression and overall survival (OS).
- •Pan-cancer co-altered STK11/KRAS did worse, regardless of treatment type.
- •STK11 alterations alone did not associate with inferior immunotherapy outcome.
- •STK11 and KRAS and TP53 mutations had a significantly shorter PFS and OS.
Abstract
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 median 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 immunotherapy,
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.
Keywords
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Article info
Publication history
Published online: March 19, 2021
Accepted:
January 29,
2021
Received in revised form:
December 24,
2020
Received:
August 13,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
