Prognostic Impact of KRAS Mutation Status for Patients with Stage IV Adenocarcinoma of the Lung Treated with First-line Pembrolizumab Monotherapy

Objectives: Monotherapy with pembrolizumab is the preferred first-line treatment for metastatic non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression ≥50 %, without targetable oncogenic drivers. Although targeted therapies are in development for patients with specific Kirsten rat sarcoma (KRAS) mutations, these are not available in daily care yet. It is not clear whether there is a difference in survival on first-line pembrolizumab for patients with a high PD-L1 status with or without a KRAS mutation. We aim to compare this survival based on real-world data.

Materials And Methods: This is a real-world retrospective population-based study using data from the Netherlands Cancer Registry. We selected patients with stage IV lung adenocarcinoma with PD-L1 expression ≥50 % diagnosed between January 2017 and December 2018, treated with first-line pembrolizumab. Patients with EGFR mutations, ALK translocations or ROS1 rearrangements were excluded. The primary outcome parameter was overall survival.

Results: 388 (57 %) of 595 patients had a KRAS mutation. KRAS was seen more frequently in women than in men (65 % versus 49 % respectively, p < 0.001). The median overall survival was 19.2 months versus 16.8 months for patients with and without KRAS mutation, respectively (p = 0.86). Multivariable analysis revealed WHO performance score, number of organs with metastases and PD-L1 percentage as independent prognostic factors. KRAS mutation status had no prognostic influence (hazard ratio = 1.03, 95 % CI 0.83-1.29).

Conclusion: The survival of KRAS mutated versus KRAS wild-type lung adenocarcinoma patients, treated with first-line pembrolizumab monotherapy, is similar, suggesting that KRAS has no prognostic value with respect to treatment with pembrolizumab.