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Mutations Linked to Poorer Outcomes in Lung Cancer Identified in MYSTIC Trial

By: Lauren Harrison, MS
Posted: Monday, November 4, 2019

Patients with metastatic non–small cell lung cancer (NSCLC) who have mutations in the genes STK11 or KEAP1 seem to have poorer outcomes across treatment groups than patients without these mutations. In addition, among patients who received the anti–PD-L1 agent durvalumab plus the anti–CTLA-4 agent tremelimumab, a mutation in ARID1A was associated with survival benefits compared with wild-type ARIDA. Naiyer A. Rizvi, MD, of Columbia University Medical Center in New York, presented these exploratory data from the MYSTIC trial at the International Association for the Study of Lung Cancer (IASLC) 2019 World Conference on Lung Cancer in Barcelona (Abstract OA04.07).

The MYSTIC trial is a phase III, randomized, open-label study of durvalumab monotherapy or durvalumab plus tremelimumab versus chemotherapy as a first-line treatment of metastatic NSCLC. Circulating tumor DNA from baseline blood samples was profiled from 1,003 patients using the GuardantOMNI platform. Survival outcomes were then analyzed in patients with or without nonsynonymous somatic mutations in STK11, KEAP1, or ARID1A.

Approximately 16% of patients had a mutation in STK11, 28% in KEAP1, and 12% in ARID1A. Patients who had mutations in STK11 or KEAP1 were found to have shorter median overall survival than patients with wild-type STK11 or wild-type KEAP1 across all treatment types (durvalumab, 10.3 vs. 13.3 months; durvalumab plus tremelimumab, 4.4 vs. 11.3 months; chemotherapy, 6.7 vs. 13.1 months). In the durvalumab-plus-tremelimumab-treatment arm, patients who had mutations in ARID1A had a longer median overall survival than did patients who had ARID1A wild-type disease (23.2 vs. 9.8 months).

Disclosure: The study authors’ disclosure information may be found at wclc2019.iaslc.org.



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