STK11 alterations in the pan-cancer setting: prognostic and therapeutic implications.

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  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.