Researchers from The University of Texas MD Anderson Cancer Center have demonstrated that patients with metastatic non-squamous non-small cell lung cancer (NSCLC) harboring specific mutations in the STK11 and/or KEAP1 tumor suppressor genes were more likely to benefit from adding the immunotherapy tremelimumab to a combination of durvalumab plus chemotherapy to overcome treatment resistance typically seen in this patient population. Study results, published today in Nature, identify KEAP1 and STK11 as potential biomarkers to stratify patients most likely to benefit from the addition of CTLA-4 immune checkpoint inhibitors, including tremelimumab. In these patients, adding tremelimumab to durvalumab and chemotherapy resulted in higher overall response rates (42.
9%) relative to patients who received durvalumab plus chemotherapy (30.2%) or chemotherapy alone (28%). These findings were further substantiated in preclinical models, supporting the use of dual checkpoint inhibitors for patients with these mutations.
"STK11 and KEAP1 alterations are common in patients with NSCLC and are linked to poor clinical outcomes with current standard-of-care first-line treatments," said co-lead author Ferdinandos Skoulidis, M.D., Ph.
D., associate professor of Thoracic/Head and Neck Medical Oncology "While prior research suggested potential benefits from adding CTLA-4 inhibitors to PD-1 or PD-L1 inhibitors, we have no reliable biomarkers to predict which patients would see the best outcomes. This.