A meta-analysis of comparing EGFR-TKI with chemotherapy as the second-line treatment of NSCLC patients with wild-type EGFR.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19166-e19166 ◽  
Author(s):  
Guanghui Gao ◽  
Shengxiang Ren ◽  
Aiwu Li ◽  
Yayi He ◽  
Xiaoxia Chen ◽  
...  

e19166 Background: The efficacy of comparing the EGFR-TKI with standard chemotherapy in the second-line treatment of advanced NSCLC with wide-type EGFR were still controversial. To derive a more precise estimation of the two regimens, a meta-analysis was performed. Methods: Medical databases and conference proceedings were searched for randomized controlled trials which compared EGFR-TKI (gefitinib or erlotinib) with standard second-line chemotherapy (docetaxel or pemetrexed) in patients with NSCLC. Endpoints were overall survival, progression-free survival and overall response. Results: Three eligible trials (INTEREST, TITAN and TAILOR) were identified. Lacking for data of overall survival of TAILOR trial, So we only make a preliminary meta-analysis for overall survival. The intention to treatment (ITT) analysis demonstrated that the patients receiving EGFR-TKI had a significantly shorter progression-free survival (PFS) than patients treated with chemotherapy (hazard ratio (HR) = 1.31; 95% confidence intervals (CI) = 1.10-1.56; P = 0.002). The overall survival (OS) and overall response rate (ORR) were coparable between this two groups (HR = 0.96; 95%CI = 0.77-1.19; P = 0.69; relative risk (RR) = 0.37; 95%CI = 0.09-1.54; P = 0.17). Conclusions: Although chemotherapy had a clear superiority in PFS as second-line treatment for patients without EGFR mutations compared with EGFR-TKI, OS and ORR were equal in this two regimens. The toxicity profiles might play an important role in the decision to choose EGFR-TKI or chemotherapy. These findings still need to be verified in larger confirmatory studies in future.

2018 ◽  
Vol 8 (2) ◽  
pp. 38-45
Author(s):  
M. Yu. Fedyanin ◽  
A. A. Tryakin ◽  
S. A. Tjulandin

Objective: to assess the efficacy of anti-angiogenic agents incorporated into second-line chemotherapeutic regimens for metastatic colon cancer depending on the KRAS gene mutation status.Materials and methods. We selected completed prospective randomized controlled phase III clinical trials evaluating the efficacy of antiangiogenic agents (bevacizumab, ramucirumab and aflibercept) added to second-line chemotherapy for metastatic colon cancer with subanalysis of treatment efficacy depending on the KRAS gene mutation status. Meta-analysis was performed using the ReviewManager (RevMan) v. 5.3 (The Cochrane Collaboration, Denmark).Results. Three studies (ML18147, RAISE, VELOUR) involving 2165 patients (1137 with KRAS wild-type tumors and 1028 with KRAS-mutant tumors) met the inclusion criteria and were included into this meta-analysis. The majority of patients (84 %) received bevacizumab in the first-line treatment. The results of our meta-analysis suggest that adding an anti-angiogenic drug to chemotherapy in patients with KRAS wildtype colon cancer significantly improved both progression-free survival (hazard ratio (HR) 0.71; 95 % confidence interval (CI) 0.62–0.80; р<0.00001; I2 = 22 %, p = 0.21) and overall survival (HR 0.76; 95 % CI 0.66–0.88; р= 0.0001; I2 = 0, p = 0.59). In patients with KRASmutant colon cancer, incorporation of an anti-angiogenic drug into the treatment regimen was not associated with better overall survival (ОР0.9; 95 % CI 0.79–1.03; р= 0.11; I2 = 0, p = 0.98), although improved progression-free survival (HR 0.78; 95 % CI 0.68–0.89; р= 0.0002; I2 = 0, p = 0.46). Conclusion. Continuation of anti-angiogenic therapy in the second-line treatment for metastatic colon cancer is most effective in patients with KRAS wild-type tumors. In individuals with KRAS-mutant tumors, continuation of bevacizumab or switch to another anti-angiogenic agent in the second-line treatment improves progression-free survival and has a statistically insignificant effect on overall survival.


2018 ◽  
Vol 33 (4) ◽  
pp. 372-378 ◽  
Author(s):  
Yuanyuan Hu ◽  
Jie Shen ◽  
RuiKe Liu ◽  
ZhiMei Feng ◽  
ChangNing Zhang ◽  
...  

Background: The pretreatment prognostic nutritional index has been considered a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC), but this remains controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of the prognostic nutritional index in patients with NSCLC. Methods: We systematically searched PubMed, EMBASE, Web of Science, and CNKI. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between the prognostic nutritional index and the oncological outcomes of patients with NSCLC, including overall survival, disease-free survival/recurrence-free survival, and progression-free survival. Results: Fifteen studies were included in this meta-analysis. Twelve of these studies explored the association between the prognostic nutritional index and the overall survival of patients with NSCLC. Our pooled analysis indicated that a low prognostic nutritional index was significantly related to adverse overall survival (HR 1.61; 95% CI 1.44, 1.81; P < 0.001). Our results also showed that the prognostic nutritional index was a negative predictor for disease-free survival/recurrence-free survival, and progression-free survival in patients with NSCLC. Conclusion: Our meta-analysis demonstrated that there was a close association between the prognostic nutritional index value and prognosis in NSCLC patients and that the prognostic nutritional index may act as a useful prognostic biomarker in NSCLC patients.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8042-8042 ◽  
Author(s):  
Jinji Yang ◽  
Ying Cheng ◽  
Mingfang Zhao ◽  
Qing Zhou ◽  
Hong hong Yan ◽  
...  

8042 Background: Pemetrexed or gefitinib is one of the standard second-line treatments for advanced non-squamousNSCLC in East Asia. The CTONG 0806 a multi-center, randomized, controlled, open-label phase II trial was designed to explore the efficacy of pemetrexed versus gefitinib as the second-line treatment in advanced NSCLC patients without EGFR mutation. Methods: The patients with locally advanced or metastatic, non-squamous NSCLC previously treated with platinum-based chemotherapy and no EGFR mutation in exons 18-21 were enrolled. Patients were 1:1 randomized to receive either gefitinib 250 mg per oral every day (G arm) or pemetrexed 500 mg/m2 iv day 1 with vitamin B12 and folic acid supplement every 21 days (P arm) until disease progression, unacceptable toxicity, or discontinuation of treatment due to other reason. The primary endpoint was progression-free survival (PFS). The secondary endpoints were 4-month and 6-month progression-free survival rate, overall survival (OS), objective response rate (ORR), quality of life using the FACT-L questionnaire and safety, EGFR and K-ras mutation status were evaluated and correlated with outcomes. Results: From Feb. 2009 to Aug. 2012, 157 evaluable patients were randomized (81 cases in G arm and 76 in P arm). Baseline age, gender, and ECOG performance status were balanced between arms. The primary endpoint of PFS was met with 1.6 months for G arm versus 4.8 months for P arm, the HR is 0.51 (95% CI 0.36~0.73, P<0.001). Overall response rates were 14.7 % and 13.3 % (P=0.814) and DCR were 32.0% and 61.3% (P<0.001) for G arm and P arm, respectively. OS data were not yet mature. More skin rash and diarrhoea were seen in G arm, but more fatigue and ALT increased in P arm. CTCAE grade 3 or 4 of AEs was 12.3% in G arm and 32.9% in P arm (p=0.002). The further analyses of efficacy evaluated by IRR and biomarkers analysis will be presented on the ground. Conclusions: CTONG0806 is the first trial to show significant improvements in PFS and DCR with pemetrexed compared with gefitinib in second-line setting for advanced NSCLC with EGFR wild type. Patients with EGFR wild type did not benefit from EGFR TKI gefitinb in second-line setting. Clinical trial information: NCT00891579.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9506-9506 ◽  
Author(s):  
Makoto Maemondo ◽  
Tatsuro Fukuhara ◽  
Haruhiro Saito ◽  
Naoki Furuya ◽  
Kana Watanabe ◽  
...  

9506 Background: In NEJ026, a phase III trial comparing bevacizumab plus erlotinib (BE) to erlotinib monotherapy (E) for EGFR-mutated non-small-cell lung cancer (NSCLC), we demonstrated the progression-free survival (PFS) of BE was significantly superior to E (Saito et al. Lancet Oncol. 2019 May;20(5):625-635.). However overall survival analysis were immature at the cutoff date. Methods: Chemotherapy-naïve pts with advanced non-squamous NSCLC harboring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. Results: The 226 pts were assigned to BE (n=112) and E (n=114). For the follow-up OS analysis, the data cut-off date was 30 November 2019. Median follow up time was 39.2 months. Median OS was 50.7 months (95% CI, 37.3 months to not reached) with BE and 46.2 months (95% CI, 38.2 months to not reached) with E (hazard ratio, 1.00; 95% CI, 0.68 to 1.48). Twenty-nine patients (25.9%) in BE and twenty-six patients (23.2%) in E were treated by osimertinib as second line treatment. The median survival time between enrollment and progressive disease of second-line treatment (median PFS2) was 28.6 months (95% CI, 22.1 months to 35.9) with BE and 24.3 months (95% CI, 20.4 months to 29.1 months) with E (hazard ratio, 0.80; 95% CI, 0.59 to 1.10). In both arms, the median OS of patients with osimertinib second-line treatment were longer than other second-line chemotherapy groups [50.7 months (95% CI, 38.0 months to 50.7 months) vs 40.1 months (95% CI, 29.5 months to not reached), (hazard ratio, 0.645; 95% CI, 0.40 to 1.03), respectively. Conclusion: The additional effect of bevacizumab on erlotinib monotherapy for NSCLC with EGFR mutations gradually decreased in the order of PFS2 and survival, with no significant differences. Clinical trial information: UMIN000017069 .


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21600-e21600
Author(s):  
Xiaoyang Zhai ◽  
Yaru Tian ◽  
Weiwei Yan ◽  
Ning An ◽  
Hui Zhu

e21600 Background: PD-1/PD-L1 inhibitor monotherapy has been approved as second line therapy in advanced non-small-cell lung cancer (NSCLC). The study aims to compare clinical outcome of PD-1 inhibitor plus chemotherapy with PD-1/PD-L1 inhibitor monotherapy as 2nd/subsequent line therapy in advanced NSCLC. Methods: The clinical data of NSCLC patients who received PD-1/PD-L1 inhibitor as 2nd/subsequent line therapy were retrospectively collected in our study. According to the therapy modality, patients were assigned to PD-1/PD-L1 inhibitor monotherapy group and PD-1 inhibitor plus chemotherapy group. Disease control rates (DCRs), progression free survival (PFS) and overall survival (OS) were evaluated between the 2 groups. The prognostic role of derived neutrophils-to-lymphocyte ratio (dNLR) on the outcomes was also evaluated at the same time. Results: From April 2017 to October 2019, a total of 84 patients were enrolled in the current study. Twenty-six patients were allocated to the PD-1/PD-L1 inhibitor monotherapy group and fifty-eight patients were allocated to PD-1 inhibitor plus chemotherapy group. Chemotherapy regimens were detailed as follow: liposome paclitaxel (n = 15), nab-paclitaxel(n = 12), docetaxel(n = 9), pemetrexed(n = 6), and others(n = 16). Disease control rates (DCRs) and overall survival (OS) were not significantly different between the two groups. Progression free survival (PFS) in the PD-1/PD-L1 inhibitor monotherapy was longer(median PFS: NR vs 4.4 months, p = 0.02). Univariate and multivariate analyses suggested that derived neutrophils-to-lymphocyte ratio (dNLR) was independent prognostic factor of OS and gender was independent prognostic factor of PFS. In the second-line therapy subgroup of 38 patients, OS and PFS were not significantly different in the two groups. In the subgroup of 46 patients of over 2nd line, PD-1/PD-L1 inhibitor monotherapy group had longer PFS (median PFS: NR vs 4.0 months, p = 0.01).The incidence of any grade adverse events (AEs) was no significant difference in the two groups. One patient in the PD-1 inhibitor plus chemotherapy group died of immune-related pneumonitis. Conclusions: The addition of chemotherapy to PD-1 inhibitor as 2nd/subsequent line therapy had similar clinical outcomes compared with PD-1/PD-L1 inhibitor monotherapy of advanced NSCLC patients.


2019 ◽  
Vol 10 (4) ◽  
pp. 3516-3522
Author(s):  
Seftika Sari ◽  
Tri Murti Andayani ◽  
Dwi Endarti ◽  
Kartika Widayati

Effectiveness data can describe the results or performance of an intervention (treatment) in daily clinical practice and also provide recommendations to policymakers regarding the need or not of health technology to be implemented into the health care system. Research related to the effectiveness of afatinib and gefitinib is still minimal, especially in Indonesia. This study aims to provide an overview of the effectiveness of afatinib and gefitinib in daily clinical practice (the real world) as first-line therapy. This research is an observational study with a retrospective approach that observes the medical records of NSCLC patients who have EGFR mutations in Dr. Sardjito General Hospital Yogyakarta and Dr. Kariadi General Hospital Semarang, Java Island, Indonesia in the period January 2016 - March 2019. The effectiveness seen is the Progress Free Survival and Overall Survival based on the patient's medical records and analyzed using the Kaplan Meier test to see survival. There were 113 patients identified, 27 patients using afatinib and 86 patients using gefitinib. Afatinib had significantly superior progression-free survival (448 days or 14.7 months; 95% CI = 12-17.4 months; p = 0.002) compared to gefitinib (344 days or 11.3 months; 95% CI = 8, 4-14.3 months), however, overall survival of afatinib is no better than gefitinib (472 days or 15.5 months; 95% CI = 13.8-17.2 months vs 653 days or 21.4 months; 95% CI = 18-24.8 months) with a value of p = 0.302. Afatinib has superior progression-free survival compared to gefitinib, but not overall survival as first-line therapy in NSCLC patients with EGFR mutations.


2021 ◽  
Author(s):  
Wen jie Xie ◽  
Shuai Zhang ◽  
Lei Su ◽  
Yan hong Li ◽  
Xi Zhang ◽  
...  

Aim: We performed an updated meta-analysis to evaluate the efficacy and safety of lenvatinib in cancer patients. Materials & methods: Databases were searched to identify relevant trials. Data were extracted to evaluate overall survival, progression-free survival, overall response rate and grade ≥3 adverse events. Results: The pooled analysis demonstrated that lenvatinib significantly improved progression-free survival (hazard ratio: 0.43; 95% CI: 0.23–0.80; p = 0.008), overall survival (hazard ratio: 0.85; 95% CI: 0.75–0.97; p = 0.013) and overall response rate (relative risk: 6.89; 95% CI: 2.22–21.36; p = 0.001) compared with control therapy. However, the use of lenvatinib can increase the risk of severe infection. Conclusion: Lenvatinib-containing regimens are associated with better progression-free survival, overall survival and overall response rate, but can induce severe infection.


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