Efficacy and safety of osimertinib in treating EGFR‐mutated advanced NSCLC: A meta‐analysis

Abstract

Osimertinib is the only Food and Drug Administration‐approved third‐generation epidermal growth factor receptor (EGFR) tyrosine‐kinase inhibitor (TKI). A meta‐analysis was performed to aggregate the mixed results of published clinical trials to assess the efficacy and safety of osimertinib. A systematic search of the PubMed, Web of Science, and Cochrane Library electronic databases was performed to identify eligible literature. The primary endpoints were overall response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and adverse events (AEs). A total of 3,086 advanced nonsmall cell lung cancer (NSCLC) patients from 11 studies have been identified. The aggregate efficacy parameters for treatment‐naïve patients with EGFR‐TKI‐sensitizing mutations are as follows: ORR 79% (95% CI 75–84%), DCR 97% (95% CI 95–99%), 6‐month PFS 83% (95% CI 80–87%), and 12‐month PFS 64% (95% CI 59–69%). The aggregate efficacy parameters for advanced NSCLC harboring T790M mutations after earlier‐generation EGFR‐TKI therapy are as follows: ORR 58% (95% CI 46–71%), DCR 80% (95% CI 63–98%), 6‐month PFS 63% (95% CI 58–69%), and 12‐month PFS 32% (95% CI 17–47%). EGFR‐TKI‐naïve patients with EGFR‐positive mutations tend to have longer median PFS than EGFR‐TKI‐pretreated counterparts (19.17 vs . 10.58 months). The most common AEs were diarrhea and rash, of which the pooled incidences were 44 and 42%, respectively. Generally, osimertinib is a favorable treatment option for previously treated T790M mutation‐positive advanced NSCLC as well as a preferable therapy for untreated EGFR mutation‐positive advanced NSCLC. Additionally, osimertinib is well tolerated by most patients.

Osimertinib-associated ashy dermatosis–like hyperpigmentation

“…EGFR-TKIs are used effectively as a treatment for metastatic nonesmall-cell lung cancer with EGFR mutation. 1,3 First-and second-generation drugs include gefitinib, erlotinib, and afatinib. Although all have favorable efficacies, each agent differs in its affinity to EGFR.…”

“…Thus, it is associated with fewer dAEs compared with earlier-generation drugs. 3,4 Unlike immune checkpoint inhibitors (antiePD-1/PD-L1), EGFR-TKIs are rarely associated with lichenoid dermatitis. 5 Pigmentary changes caused by EGFR-TKIs are unusual.…”

First-generation EGFR-TKI plus chemotherapy versus EGFR-TKI alone as first-line treatment in advanced NSCLC with EGFR activating mutation: a systematic review and meta-analysis of randomized controlled trials

“…Inevitably, most patients who initially respond to an EGFR-TKI over 8-12 moths, eventually develop resistance to first-or second-generation drugs [6]. In order to prolong the survival outcome, combination therapy of EGFR-TKI with other therapeutic drugs is an emerging promising approach.…”

Author's Reply to: Osimertinib and jaw osteonecrosis? A case report

“…Indeed, jaw osteonecrosis was not identified as an adverse effect in our study. 1 So far, we have not encountered this rare adverse effect related to Osimertinib administration in clinical practice, and we did not find corresponding reports after consulting the relevant literature. It is a meaningful issue worthy of our attention and exploration.…”

“…A case report," in which they cited our study. 1 We read their letter with interest, and we have a few additional comments on this issue and the insights gained from their case report.…”