Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation

Josiah An; Melissa Yan; Nanmeng Yu; Adithya Chennamadhavuni; Muhammad Furqan; Sarah L Mott; Bradley T Loeffler; Timothy Kruser; Timothy L Sita; Lawrence Feldman; Ryan Nguyen; Mary Pasquinelli; Nasser H Hanna; Taher Abu Hejleh

doi:10.21037/tlcr-21-177

Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation

Transl Lung Cancer Res. 2021 Aug;10(8):3608-3615. doi: 10.21037/tlcr-21-177.

Authors

Affiliations

¹ Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
² Division of Hematology and Oncology, Indiana University Health - Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
³ Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
⁴ Turville Bay Radiation Oncology, SSM Health, Madison, WI, USA.
⁵ Department of Radiation Oncology, Northwestern Memorial Hospital, Chicago, IL, USA.
⁶ Division of Hematology and Oncology, The University of Illinois at Chicago, Chicago, IL, USA.

Abstract

Background: STK11 mutation (STK11^m ) in patients (pts) with stage IV non-small cell lung cancer (NSCLC) is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11^m in stage III NSCLC pts treated with concurrent chemoradiation (CCRT) with or without consolidation ICI is unknown.

Methods: Stage III NSCLC patients who received CCRT and had known STK11 mutational status were included in this retrospective study. The data on the STK11^m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11^w ) from the University of Iowa served as a comparison group. Patient demographics and clinical characteristics were collected. Cox regression models were used to explore the effect of STK11 mutation on survival.

Results: 75 pts with stage III NSCLC who had known STK11 mutational status were identified. 16/75 (21%) had STK11^m . 5/16 with STK11 ^m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11^m and 59 STK11^w pts were not statistically different (STK11^m vs. STK11^w ): mean age: 57 vs. 64 yrs, non-squamous histology: 8/11 (73%) vs. 37/59 (63%), KRAS mutation: 3/11 (27%) vs. 11/59 (19%), TP53 mutation: 6/11 (55%) vs. 15/59 (25%), PD-L1 ≥50%: 1/8 (13%) vs. 10/32 (31%), and consolidation ICI 6/11 (55%) vs. 17/59 (29%). Regarding the 6 STK11^m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 6 (range, 1-25) in the 17 pts with STK11^w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11^m pts was significantly worse than STK11 ^w pts (HR =2.25; 95% CI, 1.03-4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11^m vs. STK11^w patients (HR 1.47, 95% CI, 0.49-4.38, P=0.49).

Conclusions: In stage III NSCLC patients who received CCRT, STK11^m was associated with worse PFS compared to STK11^w . Larger studies are needed to further explore the prognostic implications of STK11^m in stage III NSCLC and whether ICI impacts survival for this subgroup.

Keywords: KRAS; Non-small cell lung cancer (NSCLC); STK11; TP53; immunotherapy.

Grants and funding

T32 HL007344/HL/NHLBI NIH HHS/United States