When used in conjunction with definitive chemoradiation (CRT), the immunotherapy drug durvalumab has been shown to increase overall survival in patients with unresectable stage III non-small cell lung cancer (NSCLC). However, more information is needed about genetic factors of response and progression trends for durvalumab consolidation to improve the outcomes of patients with KRAS-driven illness as treatment options expand. Patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) who had previously undergone CRT and subsequently received durvalumab consolidation were the focus of this retrospective single-institution study.

Progression-free survival (PFS) and overall survival (OS) were compared between patients with KRAS-mutated and non-mutated malignancies from the beginning of durvalumab consolidation using Kaplan-Meier analysis. Fisher’s exact test was utilized to evaluate differences in the rates of intra- and extra-thoracic spread. Only 39 of the 74 individuals whose responses could be assessed had clinical genetic profiling done. KRAS mutations were found in the tumors of 18 patients, other actionable alterations (in EGFR, ALK, ERBB2, BRAF, MET, RET, or ROS1) were found in the tumors of 7 patients, and the tumors of 14 patients exhibited no modifications. The median progression-free survival time for the whole group was 16.1 months. The median PFS for patients with KRAS-mutated NSCLC was 12.6 months, while the median PFS for individuals with non-actionable tumors was 12.7 months (P= 0.77, log-rank). When comparing patients with KRAS-driven disease to patients with non-actionable tumors, the rate of progression outside of the thoracic cavity was shown to be considerably greater for patients with KRAS-driven disease (P= 0.015) than for patients with intrathoracic-only progression.

Durvalumab helped those with KRAS-mutated NSCLC just as much as it helped others with inoperable tumors. Unfortunately, Extrathoracic spread was also more common in patients with KRAS-mutated NSCLC than in those whose tumors were not amenable to treatment. This underlines the potential unmet requirements for new systemic treatments and surveillance approaches for KRAS-mutated advanced NSCLC.

Source: sciencedirect.com/science/article/pii/S1525730422001735