TY - JOUR
T1 - Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation
AU - An, Josiah
AU - Yan, Melissa
AU - Yu, Nanmeng
AU - Chennamadhavuni, Adithya
AU - Furqan, Muhammad
AU - Mott, Sarah L.
AU - Loeffler, Bradley T.
AU - Kruser, Timothy Joseph
AU - Sita, Timothy L.
AU - Feldman, Lawrence
AU - Nguyen, Ryan
AU - Pasquinelli, Mary
AU - Hanna, Nasser H.
AU - Hejleh, Taher Abu
N1 - Funding Information:
This work was supported by grants from the United States Public Health Service (CA 12428 and GM 19010), the American Cancer Society (NPI61B and NP 174), and by con-tracts with the United States Department of Energy \[EY-76-5-03-0326 (PA7 and 32)\]. We thank Richard Cone for instruction in several of the analytical procedures. K. Sato and M. Sekiguchi, J. Mol. Biol. 102, 15 (1976). a S. Yasuda and M. Sekiguchi, Proc. Natl. Acad. Sci. U.S.A. 67, 1839 (1970).
Publisher Copyright:
© Translational Lung Cancer Research. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - Background: STK11 mutation (STK11m) in patients (pts) with stage IV NSCLC is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11m 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 STK11m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11w) 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 STK11mutation on survival. Results: 75 pts with stage III NSCLC who had known STK11mutational status were identified. 16/75 (21%) had STK11m. 5/16 with STK11m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11m and 59 STK11w pts were statistically insignificant (STK11m vs. STK11w): 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 STK11m 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 STK11w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11m pts was significantly worse than STK11w pts (HR =2.25; 95% CI, 1.03–4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11m vs. STK11w patients (HR 1.47, 95% CI, 0.49–4.38, P=0.49). Conclusions: In stage III NSCLC patients who received CCRT, STK11m was associated with worse PFS compared to STK11w. Larger studies are needed to further explore the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.
AB - Background: STK11 mutation (STK11m) in patients (pts) with stage IV NSCLC is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11m 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 STK11m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11w) 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 STK11mutation on survival. Results: 75 pts with stage III NSCLC who had known STK11mutational status were identified. 16/75 (21%) had STK11m. 5/16 with STK11m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11m and 59 STK11w pts were statistically insignificant (STK11m vs. STK11w): 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 STK11m 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 STK11w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11m pts was significantly worse than STK11w pts (HR =2.25; 95% CI, 1.03–4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11m vs. STK11w patients (HR 1.47, 95% CI, 0.49–4.38, P=0.49). Conclusions: In stage III NSCLC patients who received CCRT, STK11m was associated with worse PFS compared to STK11w. Larger studies are needed to further explore the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.
KW - Immunotherapy
KW - KRAS
KW - Non-small cell lung cancer
KW - STK11
KW - TP53
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U2 - 10.21037/tlcr-21-177
DO - 10.21037/tlcr-21-177
M3 - Article
C2 - 34584860
AN - SCOPUS:85114117897
VL - 10
SP - 3608
EP - 3615
JO - Translational Lung Cancer Research
JF - Translational Lung Cancer Research
SN - 2226-4477
IS - 8
ER -
