Secondary sarcopenia is defined as a decrease in muscle mass due to disease or malnutrition. Several studies have reported that secondary sarcopenia is an indicator of postoperative recurrence. We hypothesized that there is a correlation between the effect of immune checkpoint inhibitors (ICIs) and sarcopenia. We retrospectively analyzed 38 patients with advanced non-small cell lung cancer (NSCLC) who were treated with ICIs between February 2016 and April 2018. Patients were divided into two groups according to the change rate of the psoas major muscle area (PMMA) at the L2–L3 position and investigated the correlation between the change rate of the PMMA and the efficacy of ICIs was investigated. The objective response and disease control rates were lower in patients with sarcopenia than in those without sarcopenia. Patients with sarcopenia exhibited a significantly shorter median progression-free survival (PFS) than non-sarcopenia patients. Moreover, focusing on good Eastern Cooperative Oncology Group performance status patients, sarcopenia patients showed a shorter PFS than non-sarcopenia patients. Patients with sarcopenia are associated with poor outcomes for immunotherapy among those with advanced NSCLC, based on retrospective analysis. Further research is needed to validate the clinical biomarkers involved in ICI responders.
Background
Treatment with epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) leads to initial response in most patients with EGFR‐mutated non‐small cell lung cancer (NSCLC). In contrast, little is known of the subpopulation of patients with NSCLC with EGFR mutations who exhibit clinical outcomes that require treatment with immune checkpoint inhibitors (ICIs). Therefore, to identify eligible cases to treat with ICIs, we retrospectively analyzed the correlation between clinical features and the efficacy of ICIs in patients with EGFR mutations.
Patients and Methods
We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who were treated with ICIs after developing resistance to EGFR‐TKIs between February 2016 and April 2018 at 6 institutions in Japan. The association between clinical outcomes and the efficacy of ICIs was investigated.
Results
We enrolled 27 patients who harbored EGFR‐activating mutations. The objective response and disease control rates were higher in patients with uncommon EGFR mutations than in those with common EGFR mutations (71% vs 35.7% and 57% vs 7%, P = 0.14 and P < 0.01, respectively). Patients with uncommon EGFR mutations or without T790M mutations exhibited a significantly longer median progression‐free survival than those with common EGFR mutations or with T790M mutations (P = 0.003 and P = 0.03, respectively).
Conclusion
Patients with uncommon EGFR mutations and without T790M mutations are associated with the best outcomes for treatment with immunotherapy among those with EGFR‐mutated NSCLC, based on retrospective analysis. Further research is needed to validate the clinical biomarkers involved in ICI responders with EGFR mutations.
Cancer immunotherapy, including atezolizumab monotherapy, is a promising alternative strategy for patients with advanced non-small-cell lung cancer (NSCLC). Several inflammatory indices have been reported as potential biomarkers regarding the effectiveness of various treatments. This study aimed to analyze the efficacy of atezolizumab monotherapy using baseline inflammatory markers in NSCLC patients. We retrospectively enrolled 81 NSCLC patients who received atezolizumab monotherapy at six different medical institutions in Japan. The Cox proportional hazards model was used to assess the impact of the clinical variables, including inflammatory indexes, on clinical outcomes. Median progression-free survival (PFS) and overall survival (OS) were 60 days and 252 days, respectively. The objective response rate was 7.4%, and the disease control rate was 54.3%. Patients with high neutrophil to lymphocyte ratio (NLR), low lymphocyte to monocyte ratio (LMR), and/or high platelet to lymphocyte ratio (PLR), at baseline, demonstrated substantially shorter PFS and OS compared to those with a low NLR, high LMR, and/or low PLR. The multivariate analysis demonstrated that a high baseline NLR was substantially associated with short PFS and short OS. Our retrospective observations suggest that inflammatory indices may be a potential negative prognostic factor of atezolizumab monotherapy outcomes in NSCLC patients.
Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors rarely elicit complete responses in patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC), as a small population of tumor cells survives due to adaptive resistance. Therefore, we focused on the mechanisms underlying adaptive resistance to lorlatinib and therapeutic strategies required to overcome them. We found that epidermal growth factor receptor (EGFR) signaling was involved in the adaptive resistance to lorlatinib in ALK-rearranged NSCLC, activation of which was induced by heparin-binding EGF-like growth factor production via c-Jun activation. EGFR inhibition halted ALK-rearranged lung cancer cell proliferation by enhancing ALK inhibition-induced apoptosis via suppression of Bcl-xL. Xenograft models showed that the combination of EGFR inhibitor and lorlatinib considerably suppressed tumor regrowth following cessation of these treatments. This study provides new insights regarding tumor evolution due to EGFR signaling after lorlatinib treatment and the development of combined therapeutic strategies for ALK-rearranged lung cancer.
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