Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer.

INTRODUCTION: Patients with metastatic EGFR-mutant NSCLC inevitably have disease progression while on tyrosine kinase inhibitor (TKI) therapy. Co-occurring tumor suppressor gene (TSG) alterations have been associated with poor outcomes, however, detailed analyses of their impact on patient outcomes are limited. METHODS: Patients with EGFR-mutant NSCLC treated with EGFR TKIs who had tumor genomic profiling were included. Alterations in TP53 and five additional TSGs (RB1, NF1, ARID1A, BRCA1, and PTEN) were used to stratify the cohort into the following three subgroups: patients with tumors harboring a TP53 mutation plus a mutation in at least one additional TSG (TP53mut/TSGmut), those having a TP53 mutation without additional TSG mutations (TP53mut/TSGwt), and those with TP53wt. Patient characteristics and clinical outcomes were assessed in two independent cohorts. RESULTS: A total of 101 patients from the Yale Cancer Center and 182 patients from the American Association for Cancer Research Project GENIE database were included. In the Yale cohort, TP53 mutations were identified in 65 cases (64%), of which 23 were TP53mut/TSGmut and 42 were TP53mut/TSGwt. Although the presence of a TP53 mutation was associated with worse outcomes, the additional TSG alteration in TP53mut tumors identified a subset of patients associated with particularly aggressive disease and inferior clinical outcome in both the Yale and the GENIE cohorts. Specifically, in the Yale cohort for patients receiving first-line TKIs, those with TP53mut/TSGmut tumors had shorter progression-free survival (PFS) and overall survival (OS) than TP53mut/TSGwt (PFS: hazard ratio [HR] = 2.03, confidence interval [CI]: 1.12-3.69, p < 0.01, OS: HR = 1.58, CI: 0.82-3.04, p = 0.12) or TP53wt cases (PFS: HR 2.4, CI: 1.28-4.47, p < 0.001, OS: HR = 2.54, CI: 1.21-5.34, p < 0.005). Inferior outcomes in patients with TP53mut/TSGmut tumors were also found in those receiving osimertinib as second-line therapy. Similar findings were seen in patients in the GENIE cohort. CONCLUSIONS: Patients with TP53mut/TSGmut tumors represent a patient subgroup characterized by an aggressive disease phenotype and inferior outcomes on EGFR TKIs. This information is important for understanding the biological underpinnings of differential outcomes with TKI treatment and has implications for identifying patients who may benefit from additional therapeutic interventions beyond osimertinib monotherapy.

Durvalumab Immunotherapy: Nursing Management of Immune-Related Adverse Events During the Journey of Patients With Stage III Non-Small Cell Lung Cancer.

BACKGROUND: When resection is not an option, platinum-based chemoradiotherapy (CRT) has been the historic standard of care in non-small cell lung cancer (NSCLC). Prognosis remains poor with CRT alone. Durvalumab has shown significant improvement (versus placebo) in progression-free and overall survival in patients with unresectable stage III NSCLC without progression following CRT. OBJECTIVES: This article aims to provide an overview of the efficacy and safety outcomes with durvalumab in patients with stage III NSCLC and identify management strategies for potential adverse events (AEs). METHODS: A review of published literature and guidelines was performed to evaluate durvalumab clinical outcomes and AE management strategies. FINDINGS: Durvalumab has established efficacy in patients with unresectable stage III NSCLC and is now the standard of care following CRT. Nurses need to be trained to recognize potential immune-related AEs in patients treated with immune checkpoint inhibitors.

Safety of checkpoint inhibitors for cancer treatment: strategies for patient monitoring and management of immune-mediated adverse events.

Immune checkpoint inhibitors (ICPIs), in the form of monoclonal antibodies against CTLA-4, PD-1, and PD-L1, have dramatically changed the treatment approach in several advanced cancers. Due to their mechanism of action, these novel agents are associated with a unique spectrum of immune-mediated adverse events (imAEs), with a safety profile that indicates they are better tolerated than traditional chemotherapeutic agents. This article aims to provide education on the current knowledge about imAEs associated with ICPI treatment, including strategies and tools for the prompt identification, evaluation, and optimal management of these events. The identification and management of imAEs are reviewed based on published literature, labeling guidelines, and the authors' personal experience with patients. The imAE safety profiles of ICPIs vary, depending on the specific antibody and the type of cancer being treated. Although most imAEs are mild and easily managed, early identification and proactive treatment are essential actions serving both to reduce the risk of developing severe imAEs and to maximize the potential for patients to receive the benefits of ongoing ICPI treatment. As a primary point of contact for patients undergoing oncology treatment, nurses play a critical role in identifying imAEs, educating patients about the importance of timely reporting of potentially relevant symptoms, and assisting in the treatment and follow-up of patients who develop imAEs while on ICPI therapy.