Systems assessment of intercalated combination of chemotherapy and EGFR TKIs versus chemotherapy or EGFR TKIs alone in advanced NSCLC patients

Yan, Han; Li, Qin; Wang, Wei; Zhen, Hongchao; Cao, Bangwei

doi:10.1038/srep15355

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…The median duration of EGFR-TKI treatment was 20 months, which was comparable with the results of the CTONG1104 (21.9 months) [20] and SELECT (20.0 months) studies [22]. However, the median duration was longer than that reported in the RADIANT study (11.9 months) [23]. Although a series of randomized controlled trials and retrospective studies have been carried out to evaluate the effect of adjuvant EGFR-TKIs after complete resection of lung cancer, further research is needed in patients with resected stage IIIA-N2 NSCLC.…”

Section: Discussionsupporting

confidence: 76%

Optimal Adjuvant Therapy in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer Harboring EGFR Mutations

Wen

Wang

et al. 2020

Oncol Res Treat

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Background: Some non-small-cell lung cancer (NSCLC) patients are unexpectedly diagnosed with stage IIIA-N2 disease at the time of thoracoscopy or thoracotomy. Because of the limited statistical evidence of induction chemotherapy for these patients, it is necessary to develop more profound treatment strategies. Methods: The demographic and clinical characteristics of patients with stage IIIA-N2 NSCLC harboring epidermal growth factor receptor (EGFR) mutations after radical resection were retrospectively reviewed. The patients were divided into 3 groups based on treatment: EGFR tyrosine kinase inhibitors (EGFR-TKIs, erlotinib or gefitinib), adjuvant chemotherapy (docetaxel plus cisplatin), and combination treatment (chemotherapy plus EGFR-TKIs). The effect of adjuvant therapy on survival rate was assessed using univariate and Cox regression analyses. Results: Patients receiving EGFR-TKIs alone showed significantly improved disease-free survival (DFS; p = 0.025) when compared to those receiving chemotherapy alone. Compared to chemotherapy alone, the combination of chemotherapy and EGFR-TKIs resulted did not significantly improve DFS (p < 0.001) and overall survival (OS p < 0.001). The combination of EGFR-TKIs with chemotherapy as adjuvant therapy led to improvements in both DFS (p = 0.116) and OS (p = 0.039) compared to patients receiving a EGFR-TKI monotherapy. Toxicities were mild in the 3 treatment groups. Conclusions: Our study demonstrated that adjuvant EGFR-TKI treatment significantly increased the DFS of patients with stage IIIA-N2 NSCLC when compared with cisplatin-based chemotherapy. The use of EGFR-TKIs and chemotherapy is recommended in the setting of combined-modality therapy.

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Section: Discussionsupporting

confidence: 76%

Optimal Adjuvant Therapy in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer Harboring EGFR Mutations

Wen

Wang

et al. 2020

Oncol Res Treat

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“…Chemotherapy is the most widely used method of NSCLC treatments [ 26 , 27 ]. However, accumulating evidence has shown that chemotherapeutic agents, such as DOX, MMC, Cis and PTX, can induce not only severe tumour inhibition but also side effects in a dose-dependent manner [ 28 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages

Yong

Cao

et al. 2018

J Exp Clin Cancer Res

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BackgroundLysosome-associated agents have been implicated as possible chemo-sensitizers and immune regulators for cancer chemotherapy. We investigated the potential roles and mechanisms of hydroxychloroquine (HCQ) in combination with chemotherapy in lung cancer treatment.MethodsThe effects of combined treatment on non-small cell lung cancer (NSCLC) were investigated using cell viability assays and animal models. The influence of HCQ on lysosomal pH was evaluated by lysosomal sensors and confocal microscopy. The effects of HCQ on the tumour immune microenvironment were analysed by flow cytometry.ResultsHCQ elevates the lysosomal pH of cancer cells to inactivate P-gp while increasing drug release from the lysosome into the nucleus. Furthermore, single HCQ therapy inhibits lung cancer by inducing macrophage-modulated anti-tumour CD8+ T cell immunity. Moreover, HCQ could promote the transition of M2 tumour-associated macrophages (TAMs) into M1-like macrophages, leading to CD8+ T cell infiltration into the tumour microenvironment.ConclusionsHCQ exerts anti-NSCLC cells effects by reversing the drug sequestration in lysosomes and enhancing the CD8+ T cell immune response. These findings suggest that HCQ could act as a promising chemo-sensitizer and immune regulator for lung cancer chemotherapy in the clinic.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0938-5) contains supplementary material, which is available to authorized users.

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“…In a randomized study, the median PFS was significantly longer with gefitinib plus pemetrexed than gefitinib alone (18.0 vs 14.0 months; P <0.05), but median OS was similar between the two groups (34.0 vs 32.0 months; P >0.05). 29 The system assessment study by Yan et al 30 showed that compared with EGFR-TKI monotherapy, the intercalated combination of chemotherapy and EGFR-TKIs seemed to be superior to EGFR-TKIs alone in terms of PFS ( P =0.004). Another study suggested that East Asian patient treatment with pemetrexed and erlotinib combination experienced a longer median PFS compared with erlotinib or pemetrexed alone ( P =0.004 vs erlotinib; P =0.001 vs pemetrexed).…”

Section: Discussionmentioning

confidence: 99%

Combination of EGFR-TKIs with chemotherapy versus chemotherapy or EGFR-TKIs alone in advanced NSCLC patients with EGFR mutation

Wen

Xia

Sun

et al. 2018

BTT

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PurposeBoth epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy are widely applied for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, and the combination of EGFR-TKIs and chemotherapy has been used for advanced NSCLC patients; however, little is known about the efficacy of the direct comparison among them.Patients and methodsThe demographic and clinical characteristics of 92 patients harboring advanced NSCLC with EGFR mutation were retrospectively reviewed. We evaluated the effects of EGFR-TKIs, chemotherapy, and EGFR-TKIs plus chemotherapy on advanced NSCLC patients with EGFR mutations, and the efficacy of combination of chemotherapy and EGFR-TKIs vs chemotherapy or EGFR-TKIs alone in advanced NSCLC patients was evaluated.ResultsThe statistical results showed that the intercalated combination of EGFR-TKIs plus chemotherapy significantly improved progression-free survival (PFS; HR, 1.76; 95% CI 1.03–3.01; P=0.036; median, 20.5 vs 16 months) compared with EGFR-TKI monotherapy, but no difference in overall survival (OS) was observed between these two groups (HR, 1.52; 95% CI 0.81–2.83; P=0.19; median, 36 vs 29 months). However, patients who received the combination of chemotherapy and EGFR-TKIs had longer PFS (HR, 2.78; 95% CI 1.57–4.93; P<0.0001; median, 20.5 vs 12 months) as well as OS (HR, 2.86; 95% CI 1.56–5.27; P=0.001; median, 36 vs 18 months) than those who received chemotherapy alone. Toxicities were mild among the three treatment groups. Rash and diarrhea were common adverse events (AEs) in the EGFR-TKI group, anemia and nausea in the chemotherapy group, and anemia and diarrhea in the combination group.ConclusionThis study demonstrated that the combination of chemotherapy with EGFR-TKIs as first-line treatment has a significant effect on PFS in patients with advanced NSCLC whose tumors harbor activating EGFR mutations. The combination treatment had more toxicity, but was clinically manageable.

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Systems assessment of intercalated combination of chemotherapy and EGFR TKIs versus chemotherapy or EGFR TKIs alone in advanced NSCLC patients

Cited by 5 publications

References 28 publications

Optimal Adjuvant Therapy in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer Harboring EGFR Mutations

Optimal Adjuvant Therapy in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer Harboring EGFR Mutations

Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages

Combination of EGFR-TKIs with chemotherapy versus chemotherapy or EGFR-TKIs alone in advanced NSCLC patients with EGFR mutation

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