ABSTRACT
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, pâ¯<â¯0.001). The median overall survival was 19.2 months versus 16.8 months for patients with and without KRAS mutation, respectively (pâ¯=â¯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 ratioâ¯=â¯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.
Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Proto-Oncogene Proteins p21(ras) , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Antibodies, Monoclonal, Humanized , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Humans , Lung/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Netherlands , Prognosis , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Retrospective StudiesABSTRACT
Improved conflict handling is important to reduce relational discord. Touch potentially has beneficial effects on three important characteristics of conflict discussions, i.e., physiological reactivity, affect and communication behavior. We studied effects of hand-holding between partners during conflict discussions (N = 47 student couples) and after conflict discussions (N = 53 student and N = 45 clinical couples). During conflict discussions hand-holding caused lower heart rate reactivity, higher positive affect and improved communication in men, and in women lower positive affect but improved communication. After conflict discussions hand-holding resulted in lower heart rate reactivity and higher heart rate variability in student couples and higher positive affect in student and clinical couples. Touch seems a promising add-on intervention in couple therapy.
