Faculty Collaboration Database

STK11 alterations in the pan-cancer setting: prognostic and therapeutic implications. Eur J Cancer 2021 May;148:215-229

Date

03/22/2021

Pubmed ID

33744718

Pubmed Central ID

PMC10344467

DOI

10.1016/j.ejca.2021.01.050

Scopus ID

2-s2.0-85102865132 (requires institutional sign-in at Scopus site)   22 Citations

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.

Author List

Krishnamurthy N, Goodman AM, Barkauskas DA, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Circulating Tumor DNA
Female
Follow-Up Studies
Humans
Immunotherapy
Male
Middle Aged
Mutation
Neoplasms
Prognosis
Survival Rate
Young Adult