Efficacy and Safety of Pemetrexed and Gefitinib in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis

Zhang, Zhihao; Wang, Xiyong; Xiao, Huaiqing; Wu, Dongqiang; Zhang, Dongliang; Yu, Qun; Yuan, Linna

doi:https://doi.org/10.1155/2021/5534823

Computational and Mathematical Methods in Medicine

On this page

Abstract Introduction Materials and Methods Results Discussion Data Availability Consent Conflicts of Interest Authors’ Contributions References Copyright Related Articles

Special Issue

Machine Learning and Network Methods for Biology and Medicine 2021

View this Special Issue

Research Article | Open Access

Volume 2021 | Article ID 5534823 | https://doi.org/10.1155/2021/5534823

Efficacy and Safety of Pemetrexed and Gefitinib in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis

Zhihao Zhang,¹Xiyong Wang,¹Huaiqing Xiao,¹Dongqiang Wu,¹Dongliang Zhang,¹Qun Yu,¹and Linna Yuan²

Academic Editor: Tao Huang

Received04 Feb 2021

Revised22 Mar 2021

Accepted09 Apr 2021

Published21 Apr 2021

Abstract

Object. This study is aimed at evaluating the efficacy and safety of pemetrexed and gefitinib in the treatment of non-small-cell lung cancer (NSCLC). Methods. Databases, including PubMed, the Cochrane Library, Embase, CNKI, and Web of Science, were applied to search for randomized controlled trials (RCTs) about the use of pemetrexed and gefitinib in the second-line treatment of locally advanced and metastatic NSCLC from database foundation to April 2020. Meta-analysis was conducted using the RevMan 5.3 software. Primary outcomes included progression-free survival (PFS) and overall survival (OS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and all grades of drug-related adverse events (AEs). Results. Totally, 14 RCTs and 1,334 patients were involved in the study. The results of meta-analysis showed that compared with pemetrexed, gefitinib was not superior in improving ORR (), DCR (), PFS (), and OS (). Subgroup analysis showed that in patients with mutant EGFR () and wild-type EGFR (), both pemetrexed and gefitinib produced a similar effect on PFS. In terms of safety, the incidence of rash () and diarrhea () in the gefitinib group was significantly higher than those in the pemetrexed group, while the occurrence of neutropenia () and fatigue () was significantly lower. Conclusion. Gefitinib and pemetrexed showed similar efficacy and safety, regardless of the type of EGFR. Both gefitinib and pemetrexed can be used as conventional drugs for the second-line treatment of locally advanced and metastatic NSCLC.

1. Introduction

Lung cancer remains the leading cause of cancer-related deaths worldwide [1]. Non-small-cell lung cancer (NSCLC) is the most common type, accounting for about 80%-85% of all lung cancers [2]. Most patients diagnosed with NSCLC are in advanced stage or locally advanced metastatic period. Platinum-based chemotherapy is used as the standard first-line chemotherapy regimen at present for advanced NSCLC [3], but it can only take effect on 30%-40% of patients and contribute to a median survival time of only 8 to 11 months [4]. Compared with the optimal supportive treatment, platinum-based chemotherapeutics can improve patient’s overall survival (OS) and progression-free survival (PFS). However, most patients will develop drug resistance after several periods of platinum-based first-line chemotherapy, on which occasion second-line chemotherapy is recommended [5]. At present, second-line chemotherapeutics mainly include docetaxel, pemetrexed, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) (gefitinib and erlotinib) [6]. This study is aimed at comparing the efficacy and safety of pemetrexed and gefitinib in the treatment of NSCLC.

Pemetrexed is a new antifolate drug, and its combination with platinum drugs (cisplatin or carboplatin) has been widely recognized as the mainstay in first-line chemotherapy of NSCLC. Pemetrexed works by disrupting folic-acid-dependent metabolic processes that are critical to cancer cells. Gefitinib is one of the first-generation reversible EGFR-TKIs, and it is usually used in second-line or third-line treatment for advanced NSCLC [7]. In a phase II clinical trial, gefitinib was identified to have a significant antitumor effect on progressive NSCLC or on NSCLC with brain metastasis [8], with good tolerance [9]. However, it was also reported that gefitinib could not increase the OS and disease-free survival (DFS) of NSCLC patients, and more toxic reactions occurred in patients [10]. In recent years, some scholars have probed into the efficacy and safety of gefitinib and pemetrexed in the second-line treatment of advanced NSCLC, yet most of the conclusions are different and the sample size is relatively small.

This study comprehensively compared the efficacy and safety of gefitinib and pemetrexed in the second-line treatment of locally advanced and metastatic NSCLC with a systematic evaluation method. We hope that this study can provide more evidences for the rational choice of second-line drugs in the treatment of locally advanced and metastatic NSCLC.

2. Materials and Methods

2.1. Inclusion and Exclusion Criteria

2.1.1. Type

Randomized controlled trials (RCTs).

2.1.2. Objective

(1)Patients who were diagnosed with locally advanced and metastatic (stage III b or IV) NSCLC by pathology or cytology(2)Patients who had undergone at least one course of platinum-based chemotherapy but failed(3)Patients who had at least one measurable focus(4)Patients who had an ECOG PS score of 0-2(5)Patients who had no obvious contraindications to chemotherapy

2.1.3. Interventions

Gefitinib was given by oral in the test group, while pemetrexed was given for systemic chemotherapy in the control group.

2.1.4. Outcome Index

(1)Objective response rate (ORR): according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) [11], ORR is divided into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). (2)Disease control rate (DCR): (3)Progression-free survival (PFS): time (months) from the start of treatment to disease progression or the last follow-up visit without progression(4)Overall survival (OS): time (months) from the start of treatment to death due to any cause(5)Adverse events (AEs) of all grades: according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 of the National Cancer Institute [12], drug-related AEs include rash, diarrhea, neutropenia, and fatigue

2.1.5. Exclusion Criteria

(1)Non-English or non-Chinese literature(2)Repeatedly published literature(3)Patients who had already been treated by pemetrexed or gefitinib or other micromolecular TKIs(4)Patients who had been treated by gefitinib or pemetrexed as first-line treatment or maintenance treatment(5)Patients who had other small cell lung cancers or other malignant tumors

2.2. Search Strategies

Databases including PubMed, the Cochrane Library, Embase, CNKI, and Web of Science were searched to find RCTs about the use of pemetrexed and gefitinib in the second-line treatment of locally advanced and metastatic NSCLC from foundation to April 2020. The search was performed using free words and subject terms together. Retrieval keywords and related medical subject headings (MeSHs) are as follows: “gefitinib”, “pemetrexed”, and “non-small cell lung cancer”. References from the conforming articles were also searched manually to check other related articles.

2.3. Literature Screening, Data Extraction, and Evaluation of the Risk of Bias for the Included Literature

Literature screening and data extraction were done by two researchers independently. The data were cross-checked, and if there was a discrepancy, they would discuss or ask for a third party. Data were extracted with a self-designed extraction form, including (1) basic information of the included literature, such as the first author and the published year; (2) baseline characteristics, such as case number, gender ratio, age, and follow-up time; and (3) outcome indexes and measurement data. The risk of bias for the included literature was evaluated by the bias risk assessment tool recommended in Cochrane 5.1.0 [13], including random sequence generation, allocation concealment, blind evaluation, incomplete result data, selective reporting, and other biases. Each quality item is classified as low risk, high risk, or unclear risk.

2.4. Statistics Analysis

Meta-analysis was conducted using RevMan 5.3. The odds ratio (OR) was used as the effect indicator for enumeration data, and the hazard ratio (HR) was used for measurement data. The effect size was provided with a point estimate value and a 95% confidence interval (CI). The chi-square test was used to study the heterogeneity of the study results (test standard, ), and the degree was quantitatively judged by . If and , there is no statistical heterogeneity among the studies, and a fixed-effects model will be used for meta-analysis. Instead, the origin of the heterogeneity will be further explored and a random-effects model will be used for meta-analysis after obvious clinical heterogeneity is excluded. Obvious clinical heterogeneity was treated by subgroup analysis or sensitivity analysis, or descriptive analysis only. In addition, potential publication bias was assessed via visual observation on the funnel plot. The test standard of meta-analysis was set to .

3. Results

3.1. Literature Screening and Basic Characteristics of the Literature Involved in the Study

Totally, 522 references were initially obtained, 116 duplicates were eliminated, and 14 RCTs were eventually involved in the study after further screening by reading the title, the abstract, and the whole text [14–27]. The screening procedure is shown in Figure 1. Totally, 1,334 patients were involved, with 671 in the test group and 663 in the control group. Among the 14 RCTs, 6 were written in English and 8 were in Chinese. The basic characteristics of the involved studies are listed in Table 1. In addition, the risk of bias for the included studies was assessed using Cochrane’s bias risk assessment tool. Figure 2(a) shows the results of the overall risk of bias assessment, and Figure 2(b) shows the risk of bias for each included trial. The results showed that most of the included RCTs were of high quality.

(a) Overall risk of bias

(b) Risk of bias for each RCT

3.2. Meta-Analysis

3.2.1. ORR

Fourteen RCTs were involved. The results of meta-analysis using a random-effects model showed that the difference in ORR between the gefitinib group and the pemetrexed group was not statistically significant (, 95% CI (0.84, 2.20), ), as shown in Figure 3.

3.2.2. DCR

Thirteen RCTs were involved. The results of the meta-analysis using a random-effects model showed that the difference in DCR between the gefitinib group and the pemetrexed group was not statistically significant (, 95% CI (0.58, 1.32), ), as shown in Figure 4.

3.2.3. PFS and OS

Seven RCTs were involved to study patient’s PFS. The results of meta-analysis using a random-effects model showed that there was no statistically significant difference in PFS between the gefitinib group and the pemetrexed group (, 95% CI (0.53, 1.30), ) (Figure 5). In addition, subgroup analysis indicated that both gefitinib and pemetrexed showed a similar effect on PFS in patients with mutant EGFR (, 95% CI (0.12, 1.14), ) (Figure 6) and wild-type EGFR (, 95% CI (0.25, 5.96), ) (Figure 7). Five RCTs were involved to study patient’s OS. The results of meta-analysis using a random-effects model showed there was no statistically significant difference in OS between the gefitinib group and the pemetrexed group (, 95% CI (0.69, 1.33), ) (Figure 8).

3.2.4. Occurrence Rate of Rash

Thirteen RCTs were involved. The results of meta-analysis on a random-effects model showed that the occurrence rate of rash in the gefitinib group was markedly higher than that in the pemetrexed group and the difference was statistically significant (, 95% CI (5.66, 36.00), ) (Figure 9).

3.2.5. Occurrence Rate of Diarrhea

Fourteen RCTs were involved. The results of meta-analysis on a random-effects model showed that the occurrence rate of diarrhea in the gefitinib group was markedly higher than that in the pemetrexed group and the difference was statistically significant (, 95% CI (1.81, 8.41), ) (Figure 10).

3.2.6. Occurrence Rate of Neutropenia

Eleven RCTs were involved. The results of meta-analysis on a random-effects model showed that the occurrence rate of neutropenia in the gefitinib group was markedly lower than that in the pemetrexed group and the difference was statistically significant (, 95% CI (0.07, 0.73), ) (Figure 11).

3.2.7. Occurrence Rate of Fatigue

Ten RCTs were involved. The results of meta-analysis on a random-effects model showed that the occurrence rate of fatigue in the gefitinib group was markedly lower than that in the pemetrexed group and the difference was statistically significant (, 95% CI (0.19, 0.87), ) (Figure 12).

3.3. Publication Bias

Visually, the funnel plots were basically symmetrical (Figure 13), indicating that there was no publication bias in ORR, DCR, PFS, and OS.

(a) ORR

(b) DCR

(c) PFS

(d) OS

4. Discussion

As a routine therapy for NSCLC, first-line chemotherapy can prolong a patient’s lifetime to some extent, yet its efficacy in patients with advanced NSCLC is poor and patients always have an unfavorable prognosis [28]. In recent years, with the emergence and development of molecular targeted therapies, studies found that molecular targeted therapy has increasingly shown its advantages in the treatment of lung cancer. In this study, we systematically evaluated the efficacy and safety of pemetrexed and gefitinib in the second-line treatment of locally advanced and metastatic NSCLC.

Pemetrexed is a multitargeted antimetabolite drug and a thymidylate synthase/dihydrofolate reductase inhibitor. It has a strong inhibitory effect on several folate-dependent enzymes. It can inhibit the synthesis of pyrimidine and purine by many methods, thus playing an antitumor role and reducing drug resistance [29]. Pemetrexed-based second-line therapy for advanced NSCLC was reported to have similar efficacy with docetaxel but have minor toxic and side effects [30]. In 2004, pemetrexed was approved to be used in second-line treatment for advanced NSCLC by the U.S. Food and Drug Administration. Gefitinib is a peroral micromolecular EGFR-TKI. It can inhibit the EGFR signaling pathway by competing with adenosine triphosphate (ATP) to bind to the catalyze zone of receptor tyrosine kinase, thus inhibiting cancer cell proliferation and promoting tumor cell apoptosis, ultimately mediating tumor growth and prolonging a patient’s lifetime [31]. A phase III IPASS test verified that [32] gefitinib used in first-line therapy for advanced NSCLC can increase ORR and DCR and prolong PFS without severe AEs. However, gefitinib cannot be used in all patients with advanced NSCLC, and its efficacy is more obvious in the benefit population. Rosell and the fellows found when they screened EGFR mutations on 2,105 Spanish patients with lung cancer that the rate of EGFR mutation was high in nonsmoking and female patients with adenocarcinoma [33]. Women, Asians, nonsmokers, and patients with adenocarcinoma are now considered as the benefit populations of gefitinib treatment. The China Food and Drug Administration approved gefitinib for the first-line treatment of patients suffering from advanced NSCLC with EGFR-sensitive mutations on February 22, 2011. Notably, here, we found that for patients with EGFR mutation-positive NSCLC, gefitinib was not superior to pemetrexed in terms of PFS, which might be related to the predominance of the patients who smoked, had adenocarcinoma, had EGFR-sensitive mutation-negative NSCLC, or had unknown mutations in all included studies. In recent years, second-line therapy has become a hotspot in NSCLC research, and many scholars have explored the role of gefitinib as a second-line drug in the treatment of NSCLC. In order to compare the efficacy of gefitinib and docetaxel in patients with advanced NSCLC who had received first-line chemotherapy, Kim and fellows designed a phase III randomized trial (INTEREST) [34]. 1,466 patients from 24 countries and 149 hospitals were involved into this trial, and the results showed that gefitinib produced similar efficacy with docetaxel and there was no significant difference regarding OS and PFS between the two therapies. This trial identified the important role of gefitinib in the second-line treatment of NSCLC. A recent meta-analysis discussed the efficacy of gefitinib in the treatment of advanced NSCLC. The results showed that gefitinib may be more beneficial to patients with EGFR mutations compared with standard first-line or second-line chemotherapy or maintenance therapy [35]. Our study is mainly aimed at the gefitinib-based second-line treatment. However, in patients with EGFR mutations, compared with pemetrexed, gefitinib-based second-line treatment in locally advanced and metastatic NSCLC produced no benefit in PFS, while the differences in ORR, DCR, and OS between pemetrexed and gefitinib groups were not statistically significant, which is consistent with previous studies [36]. In addition, we found that in terms of AEs, the occurrence rate of rash and diarrhea in the gefitinib group was higher than that in the pemetrexed group, while the occurrence of neutropenia and fatigue in the gefitinib group was significantly lower than that of the pemetrexed group.

This study has some limitations. First of all, most studies included were conducted in China, and the results may not fully reflect the treatment situation in other countries, and the sample size is small. Second, in the included studies, there are biases in the length of follow-up time, treatment strategy, and time, which may cause the heterogeneity of clinical results to a certain extent. Although we conducted a subgroup analysis regarding the wild/mutant EGFR, there was still a large heterogeneity in the results, which may be related to the small cohort for EGFR mutations. Third, different first-line treatment methods may have an impact on final clinical outcomes. For example, a review discussed the necessity of EGFR-TKIs in first-line treatment for NSCLC, so as to provide the most effective therapeutic regimen in initial treatment [37]. Finally, meta-analysis is limited to the data provided by the original study authors. In some cases, information such as disease status, smoking status, and pathological subtype is incomplete and cannot be used for subgroup analysis.

In conclusion, gefitinib and pemetrexed for the treatment of locally advanced and metastatic NSCLC patients with failed first-line chemotherapy have similar efficacy and safety. In the future, more well-designed RCTs are needed for further verification.

Data Availability

The data used to support the findings of this study are included within the article. The data and materials in the current study are available from the corresponding author on reasonable request.

Consent is not applicable.

Conflicts of Interest

The authors declare that they have no potential conflicts of interest.

Authors’ Contributions

All authors contributed to data analysis and drafting and revising the article, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

References

R. L. Siegel, K. D. Miller, H. E. Fuchs, and A. Jemal, “Cancer statistics, 2021,” CA: a Cancer Journal for Clinicians, vol. 71, no. 1, pp. 7–33, 2021.
View at: Publisher Site | Google Scholar
W. D. Travis, A. G. Nicholson, E. Brambilla et al., “The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification,” Journal of Thoracic Oncology, vol. 10, no. 9, pp. 1243–1260, 2015.
View at: Publisher Site | Google Scholar
M. D. Hellmann, B. T. Li, J. E. Chaft, and M. G. Kris, “Chemotherapy remains an essential element of personalized care for persons with lung cancers,” Annals of Oncology, vol. 27, no. 10, pp. 1829–1835, 2016.
View at: Publisher Site | Google Scholar
F. R. Hirsch, G. V. Scagliotti, J. L. Mulshine et al., “Lung cancer: current therapies and new targeted treatments,” The Lancet, vol. 389, no. 10066, pp. 299–311, 2017.
View at: Publisher Site | Google Scholar
S. Zhou, L. Zuo, X. He, J. Pi, J. Jin, and Y. Shi, “Efficacy and safety of rh-endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh-endostatin plus pemetrexed maintenance in non-small cell lung cancer: a retrospective comparison with standard chemotherapy,” Thoracic Cancer, vol. 9, no. 11, pp. 1354–1360, 2018.
View at: Publisher Site | Google Scholar
Z. Liu, Z. Wei, Y. Hu et al., “A phase II open-label clinical study of comparing nab-paclitaxel with pemetrexed as second-line chemotherapy for patients with stage IIIB/IV non-small-cell lung cancer,” Medical Oncology, vol. 32, no. 8, p. 216, 2015.
View at: Publisher Site | Google Scholar
D. S. Ettinger, D. E. Wood, W. Akerley et al., “NCCN guidelines insights: non-small cell lung cancer, version 4.2016,” Journal of the National Comprehensive Cancer Network, vol. 14, no. 3, pp. 255–264, 2016.
View at: Publisher Site | Google Scholar
D. Kazandjian, G. M. Blumenthal, W. Yuan, K. He, P. Keegan, and R. Pazdur, “FDA approval of gefitinib for the treatment of patients with metastatic EGFR mutation-positive non-small cell lung cancer,” Clinical Cancer Research, vol. 22, no. 6, pp. 1307–1312, 2016.
View at: Publisher Site | Google Scholar
F. Cappuzzo, A. Morabito, N. Normanno et al., “Efficacy and safety of rechallenge treatment with gefitinib in patients with advanced non-small cell lung cancer,” Lung Cancer, vol. 99, pp. 31–37, 2016.
View at: Publisher Site | Google Scholar
H. Wo, J. He, Y. Zhao, H. Yu, F. Chen, and H. Yi, “The efficacy and toxicity of gefitinib in treating non-small cell lung cancer: a meta-analysis of 19 randomized clinical trials,” Journal of Cancer, vol. 9, no. 8, pp. 1455–1465, 2018.
View at: Publisher Site | Google Scholar
E. A. Eisenhauer, P. Therasse, J. Bogaerts et al., “New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1),” European Journal of Cancer, vol. 45, no. 2, pp. 228–247, 2009.
View at: Publisher Site | Google Scholar
A. Figueiredo, M. A. Almeida, M. T. Almodovar et al., “Real-world data from the Portuguese nivolumab expanded access program (EAP) in previously treated non small cell lung cancer (NSCLC),” Pulmonology, vol. 26, no. 1, pp. 10–17, 2020.
View at: Publisher Site | Google Scholar
J. P. Higgins and S. J. N.-S. Green, “Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie,” Cochrane Handbook For Systematic Reviews Of Interventions Version 5.0.0, vol. 5, Article ID S38, 2008.
View at: Google Scholar
J. Hong, S. Y. Kyung, S. P. Lee et al., “Pemetrexed versus gefitinib versus erlotinib in previously treated patients with non-small cell lung cancer,” The Korean Journal of Internal Medicine, vol. 25, no. 3, pp. 294–300, 2010.
View at: Publisher Site | Google Scholar
J. M. Sun, K. H. Lee, S. W. Kim et al., “Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial,” Cancer, vol. 118, no. 24, pp. 6234–6242, 2012.
View at: Publisher Site | Google Scholar
H. Dai, L. Xu, C. Xia, and W. Chen, “A randomized clinical study of gefitinib and pemetrexed as second line therapy for advanced non-squamous non-small cell lung cancer,” Zhongguo Fei Ai Za Zhi, vol. 16, no. 8, pp. 405–410, 2013.
View at: Publisher Site | Google Scholar
Q. Zhou, Y. Cheng, J. J. Yang et al., “Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter randomized trial,” Annals of Oncology, vol. 25, no. 12, pp. 2385–2391, 2014.
View at: Publisher Site | Google Scholar
Y. S. Kim, E. K. Cho, H. S. Woo et al., “Randomized phase II study of pemetrexed versus gefitinib in previously treated patients with advanced non-small cell lung cancer,” Cancer Research and Treatment, vol. 48, no. 1, pp. 80–87, 2016.
View at: Publisher Site | Google Scholar
Y. H. Xu, J. S. Mei, and J. Zhou, “Randomized study of gefitinib versus pemetrexed as maintenance treatment in patients with advanced glandular non-small cell lung cancer,” International Journal of Clinical and Experimental Medicine, vol. 8, no. 4, pp. 6242–6246, 2015.
View at: Google Scholar
L. Lin, J. Zhao, J. Hu et al., “Comparison of the efficacy and tolerability of gefitinib with pemetrexed maintenance after first-line platinum-based doublet chemotherapy in advanced lung adenocarcinoma: single-center experience,” OncoTargets and Therapy, vol. 9, pp. 6305–6314, 2016.
View at: Publisher Site | Google Scholar
X. M. Liu, “Clinical efficacy and safety of gefitinib versus pemetrexed second line treatment of non-small cell lung cancer,” The Chinese Journal of Clinical Pharmacology, 2015.
View at: Google Scholar
L. H. Zhao, H. Y. Wang, and D. F. Zhang, “A clinical study for gefitinib versus pemetrexed in second-line treatment of advanced non-small cell lung cancer,” Chinese Journal of Clinical Oncology and Rehabilitation, vol. 20, pp. 1235–1238, 2013.
View at: Google Scholar
T. T. Song, H. R. Gai, W. Li, and F. J. Hu, “Clinical efficacy of gefitinib in treating advanced non-small cell lung cancer,” Chinese Journal of Difficult and Complicated Cases, vol. 14, no. 8, pp. 778–781, 2015.
View at: Google Scholar
M. Q. Wang, L. X. He, D. W. Peng, S. Q. Jiang, X. Z. Cheng, and Z. Z. Xie, “A comparative study regarding pemetrexed and gefitinib in the second-line treatment for advanced NSCLC,” China Tropical Medicine, vol. 12, pp. 1361–1363, 2012.
View at: Google Scholar
D. G. Zhang and X. L. Ruan, “A clinical study for gefitinib versus pemetrexed in the second-line treatment of advanced non-small cell lung cancer,” Oncology Progress, vol. 14, no. 1, pp. 78–80, 2016.
View at: Google Scholar
J. Zhang, S. Q. Liu, J. Zhang, L. Y. Ban, and T. Zhou, “Efficacy and cost-effectiveness of different second-line treatment regimens for advanced non-small cell lung cancer,” Chinese Clinical Oncology, vol. 17, pp. 908–911, 2012.
View at: Google Scholar
Y. H. Zhang and H. B. Wang, “A clinical study on gefitinib and pemetrexed in treating advanced recurrent non-small cell lung cancer,” Chinese Journal of Clinical Rational Drug Use, vol. 2, pp. 14–16, 2009.
View at: Google Scholar
H. F. Qin, L. L. Qu, H. Liu, S. S. Wang, and H. J. Gao, “Serum CEA level change and its significance before and after gefitinib therapy on patients with advanced non-small cell lung cancer,” Asian Pacific Journal of Cancer Prevention, vol. 14, no. 7, pp. 4205–4208, 2013.
View at: Publisher Site | Google Scholar
Y. Kawano, F. Ohyanagi, N. Yanagitani et al., “Pemetrexed and cisplatin for advanced non-squamous non-small cell lung cancer in Japanese patients: phase II study,” Anticancer Research, vol. 33, no. 8, pp. 3327–3333, 2013.
View at: Google Scholar
N. Hanna, F. A. Shepherd, F. V. Fossella et al., “Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy,” Journal of Clinical Oncology, vol. 22, no. 9, pp. 1589–1597, 2004.
View at: Publisher Site | Google Scholar
Y. H. J. C. Zhang and JoCRDU, “Comparison of clinical efficacy on gefitinib vs pemetrexed as IV non-small cell lung cancer who had failed to first-line treatment,” The Chinese Journal of Clinical Pharmacology, 2009.
View at: Google Scholar
M. Fukuoka, Y. L. Wu, S. Thongprasert et al., “Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS),” Journal of Clinical Oncology, vol. 29, no. 21, pp. 2866–2874, 2011.
View at: Publisher Site | Google Scholar
R. Rosell, T. Moran, C. Queralt et al., “Screening for epidermal growth factor receptor mutations in lung cancer,” The New England Journal of Medicine, vol. 361, no. 10, pp. 958–967, 2009.
View at: Publisher Site | Google Scholar
E. S. Kim, V. Hirsh, T. Mok et al., “Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial,” The Lancet, vol. 372, no. 9652, pp. 1809–1818, 2008.
View at: Publisher Site | Google Scholar
E. H. Sim, I. A. Yang, R. Wood-Baker, R. V. Bowman, and K. M. Fong, “Gefitinib for advanced non-small cell lung cancer,” Cochrane Database of Systematic Reviews, no. 1, article CD006847, 2018.
View at: Publisher Site | Google Scholar
H. Wang, Z. Zhang, F. Liu, M. Zhou, and H. Lv, “Pemetrexed versus gefitinib as second-line treatment for advanced non-small cell lung cancer: a meta-analysis based on randomized controlled trials,” Pteridines, vol. 30, pp. 171–176, 2019.
View at: Publisher Site | Google Scholar
J. Roeper, S. Kurz, C. Grohe, and F. Griesinger, “Optimizing therapy sequence to prevent patient attrition in EGFR mutation-positive advanced or metastatic NSCLC,” Future Oncology, vol. 17, no. 4, pp. 471–486, 2021.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Zhihao Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

605

Downloads

818

Citations