Abstract
BackgroundThe role of immune checkpoint inhibitors (ICIs) in NSCLC patients with EGFR mutations are controversial. In this study, we aim to investigate the therapeutic efficacy of ICIs alone or in combination in patients with EGFR mutated NSCLC in late-line settings, and explore the factors that may predict the efficacy of ICIs.Patients and MethodsWe retrospectively collected the clinical and pathological information of 75 patients with confirmed EGFR mutations. All patients have developed acquired resistance to EGFR-TKIs, and were treated with ICIs in late line settings from January 2019 to January 2021, at Shandong Caner Hospital and Institute. Therapeutic efficacy was evaluated by tumor response and survival.ResultsThe median follow-up period was 7.3months (range 1.8-31.8 months). The overall response rate (ORR) was 8.0%, and the disease control rate (DCR) was 78.7%. The median PFS for all patients was 3.9 months (95% CI, 2.7-5.0), while the median OS was 9.9 months (95% CI, 5.3-14.6). We found that patients with longer response duration to EGFR-TKIs (≥10 months) showed a longer PFS when treated with immunotherapy compared with patients with shorter PFS-TKI (<10 months), the median PFS in two groups were 5.2 months [95%CI 4.2-6.2] and 2.8 months [2.0-3.6]) respectively (HR, 0.53, 95%CI, 0.31-0.91, P=0.005). In exploratory analysis, we found that concurrent extracranial radiotherapy and higher body mass index (BMI) are associated with longer PFS (P values are 0.006 and 0.021 respectively).ConclusionsWe found that combination regimen of immunotherapy plus chemotherapy plus antiangiogenetic agents may yield longer survival in patients with EGFR mutated NSCLC. We also found that patients with longer PFS-TKI, concurrent extracranial radiotherapy and higher BMI may benefit more from immunotherapy.
Highlights
Epidermal growth factor receptor (EGFR) mutations remains the most common driver mutations in patients with lung adenocarcinomas (LUAD), with an incidence of 50% in Asians and 9.8% in Caucasian Europeans [1, 2]
Pre-clinical evidences suggested that activation of EGFR would up-regulate the expression of progressive disease (PD)-L1 through numerous signaling pathways, including p-ERK1/2/p-cJun and JAK/STAT3, and blockade of PD-1 would improve the survival of murine models with EGFR mutated lung adenocarcinomas by promoting T cell infiltration and downregulating pro-tumorigenic cytokines [4–6]
We found that concurrent extracranial radiotherapy is associated with longer progression-free survival (PFS) (HR, 0.48, 95%CI 0.25-0.91, P=0.0404) (Figure 4A)
Summary
Epidermal growth factor receptor (EGFR) mutations remains the most common driver mutations in patients with lung adenocarcinomas (LUAD), with an incidence of 50% in Asians and 9.8% in Caucasian Europeans [1, 2]. The progression-free survival (PFS) of first- and secondgeneration EGFR-TKIs, including Gefitinib, Erlotinib, Icotinib, and Afatinib, is usually around 9-13 months, while the third generation EGFR-TKI, Osimertinib, yielded a PFS of 18.9 months. Despite these progress, drug resistance and disease progression are inevitable. ICIs, especially those targeting PD-1 and PD-L1 has been proven to be effective in patients with advanced NSCLC, their roles in patients harboring EGFR mutations are still in debate. It is welldemonstrated that ICIs alone or in combination with TKIs could not yield improvements in survival in patients with EGFR mutations compared with general unselected NSCLC patients [7–10]. We aim to investigate the therapeutic efficacy of ICIs alone or in combination in patients with EGFR mutated NSCLC in late-line settings, and explore the factors that may predict the efficacy of ICIs
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