Patients With Metastatic NSCLC Characterized by LKB1 Mutations Found Less Likely to Benefit From First-Line Chemotherapy

The following article features coverage from the IASLC 2019 World Conference on Lung Cancer meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to an analysis of “real-world” data presented at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, patients with metastatic NSCLC treated with first-line chemotherapy have worse clinical outcomes if they have disease characterized by mutations in LKB1.¹

Previous studies have identified inactivating mutations of the tumor suppressor gene, LKB1/STK11 (LKB1), as a predictor of resistance to immune checkpoint inhibitor therapy in patients with lung adenocarcinoma, particularly when comutations in in KRAS are also present.² Nevertheless, the potential prognostic role of these genomic alterations in patients treated with chemotherapy has been less well investigated.

This analysis used “real-world” data collected from patients with metastatic NSCLC treated between January 2013 and June 2017 with immune checkpoint inhibitor therapy or chemotherapy in the first- or second-line settings. Tumor specimens of all study patients had been analyzed using comprehensive genomic profiling, and all included patients were enrolled from the Flatiron Health Oncology database of electronic medical records.

Of the 2407 patients included in the analysis, 1847 patients had disease characterized by nonsquamous histology. Mutations in LKB1 and comutations in KRAS/LKB1 were present in the tumor specimens of 13.6% and 6.5% of patients, respectively.

For the overall study population, overall survival and progression-free survival were significantly worse for patients with disease characterized by either LKB1 or KRAS/LKB1 mutations who were treated with immune checkpoint inhibitor in the second-line setting, or with chemotherapy in the first-line, but not the second-line, setting. Similar findings with respect to these tumor mutation groups were observed for the subgroup of patients with nonsquamous disease.

“Results of this real-world study support previous clinical findings and suggest unique relevance of these mutations in first-line chemotherapy …” the study authors noted in conclusion.

Read more of Cancer Therapy Advisor‘s coverage of the IASLC annual meeting by visiting the conference page.

References

1. Shire N, Golozar A, Collins J, et al. LKB1 mutations in metastatic non-small cell lung cancer (mNSCLC): Prognostic value in the real world. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA07.02.
2. Skoulidis F, Hellmann MD, Awad MM, et al. STK11/LKB1 co-mutations to predict for de novo resistance to PD-1/PD-L1 axis blockade in KRAS-mutant lung adenocarcinoma. J Clin Oncol. 2017;35(suppl_15_abstr 9016).