Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer.

Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective for treatment of EGFR- or ALK-mutated lung cancer. Nevertheless, they are associated with several unique toxicities. Although the available US Food and Drug Administration (FDA)-approved drug label can provide guidance for safety monitoring, its integration into clinical practice has not been previously described. We studied the conduct of safety monitoring activity (SMA) at a large academic institution. On the basis of FDA-approved drug labels, two drug-specific SMAs were identified for osimertinib, crizotinib, alectinib, or lorlatinib. Electronic medical records of patients initiated on these drugs from 2017 to 2021 were retrospectively reviewed. Each course of treatment was evaluated for the occurrence of SMAs and the corresponding adverse events. Analyses included 130 treatment courses from 111 unique patients. For each SMA evaluated, the prevalence of SMA conduct ranged from 10.0% to 84.6%. The most frequently conducted SMA was ECG for lorlatinib therapy and the least was creatine phosphokinase analysis for alectinib. We observed none of the assessed SMAs being conducted in 41 treatment courses (31.5%). EGFR inhibitor predicted a higher likelihood of both SMAs being conducted than ALK inhibitors (P = .02). Serious, grade 3 or 4 adverse events were observed in 21 treatment courses (16.2%), including one grade 4 transaminitis related to alectinib. On the basis of our experience, the conduct of SMA was more challenging to implement for ALK inhibitor than for EGFR inhibitor. Clinicians should be vigilant and review the FDA-approved drug label before prescribing.

Efficacy of tyrosine kinase inhibitors against lung cancer with EGFR exon 18 deletion: Case report and pooled analysis.

BACKGROUND: Within the exon 18 of EGFR, a complex, in-frame deletion-delE709_T710ins-has been described among pulmonary adenocarcinomas with an estimated prevalence of 0.3%. Available evidences suggest that some EGFR tyrosine kinase inhibitors (TKI) have activity against this cancer. However, due to the rarity of this mutation, it remains unclear which TKI is the most effective. METHODS: We reported our experience using afatinib followed by osimertinib in a patient with this mutation. We performed a systematic review of literature and conducted a pooled analysis to compare the outcomes of treatment with first generation TKIs vs. afatinib. Cases with compound mutations were excluded. RESULTS: Our patient achieved a partial response to afatinib with a progression-free survival of 11 months. Upon disease progression, osimertinib failed to control the disease. Literature review identified 14 cases being reported: 8 received first generation TKI and 6 received afatinib. Among those with tumor response assessed, partial response occurred in 2 out of 7 patients (28.6%) treated with first generation TKI compared with 6 out of 6 patients (100%) treated with afatinib, p = 0.03. The median progression-free survival (PFS) was 3.1 months vs. 7.0 months, respectively, p = 0.005. Insufficient evidences were available to assess for the efficacy of osimertinib. CONCLUSION: Based on currently available data, afatinib was associated with a greater tumor response rate and a longer PFS than the first generation TKIs.