Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations

Abstract

Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR -mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR -activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients.

Concomitant Gastric Acid Suppressants on the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Meta-Analysis

“…Studies. Inclusion criteria were (1) observational studies published as full-length articles; (2) included adult patients (18 years or above) with a confirmed diagnosis of NSCLC treated with EGFR-TKIs; (3) patients with concomitant use of AS, including PPIs and H2RAs, who considered as exposure; (4) compared progression-free survival (PFS) or overall survival (OS) between patients with and without concomitant use of AS; and (5) reported relative risk for the association between concomitant use of AS and survival outcomes in multivariate analysis including possible confounding factors. e definition of concomitant use of AS was consistent with the criteria adopted in the original articles.…”

“…The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become an effective treatment for patients with non-small-cell lung cancer (NSCLC) [ 1 , 2 ]. For patients with NSCLC with EGFR mutations, TKIs have been reported to confer better survival benefits than conventional cytotoxic anticancer therapies [ 3 ].…”

“…2 = 0.00; Chi 2 = 0.09, df = 1 (P = 0.76); I 2 = 0% Test for overall effect: Z = 7.89 (P < 0.00001) Heterogeneity: Tau 2 = 0.22; Chi 2 = 23.52, df = 4 (P < 0.0001); I 2 = 83% Test for overall effect: Z = 2.06 (P = 0.04) Heterogeneity: Tau 2 = 0.08; Chi 2 = 27.14, df = 7 (P = 0.0003); I 2 = 74% Test for overall effect: Z = 4.03 (P = 0.0001) Heterogeneity: Not applicable Test for overall effect: Z = 1.10 (P = 0.27)…”

RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With EGFR-Mutated Metastatic NSCLC

“…EGFR tyrosine kinase inhibitors (TKIs) are standard-of-care first-line treatment for EGFR- mutated NSCLC. 6 , 7 , 8 Nevertheless, many patients eventually develop treatment resistance and experience disease progression on EGFR TKI therapy. Approximately 30% to 60% of patients with NSCLC treated with first- and second-generation EGFR TKIs acquire the EGFR T790M resistance mutation, whereas resistance mechanisms to the third-generation EGFR TKI osimertinib (OSI) are heterogeneous and mostly not targetable.…”

Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR‑mutant lung cancer with HIF‑1α/TGF‑α expression

“…In particular, epidermal growth factor receptor ( EGFR ) gene mutations are the most frequent driver mutations in never-smokers or individuals with Asian ethnicity. EGFR tyrosine kinase inhibitors (TKIs) are standard therapies for patients with lung cancer harboring EGFR mutations ( 1 , 2 ); however, their inhibitory effects are insufficient to achieve complete remission and acquired resistance usually develops within two years ( 2 ). The third-generation EGFR-TKI osimertinib is the standard of care for patients with NSCLC harboring EGFR T790M, which is the most common mechanism of resistance for first- or second-generation EGFR-TKIs.…”