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Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non-Small Cell Lung Cancer: A Meta-Analysis.

Xu JL, Jin B, Ren ZH, Lou YQ, Zhou ZR, Yang QZ, Han BH - PLoS ONE (2015)

Bottom Line: Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01).Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06).In addition, intercalated administration is an effective combinatorial strategy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.

ABSTRACT

Background: Whether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC.

Methods: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015).

Results: Nine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06).

Conclusion: Combination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation-positive disease. In addition, intercalated administration is an effective combinatorial strategy.

No MeSH data available.


Related in: MedlinePlus

Flow Diagram of Included and Excluded Studies.
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pone.0131278.g001: Flow Diagram of Included and Excluded Studies.

Mentions: A total of 1597 articles were identified by the initial search strategy. After excluding irrelevant studies, review articles, RCTs without adequate data, meta-analyses, observational studies, single arm trials and case reports, nine trials were finally included for this meta-analysis (S1 File shows a list of full-text excluded articles). The selection steps are summarized in the flow chart shown in Fig 1. These trials enrolled a total of 3599 patients. Among them [8–16], four trials were placebo-controlled double-blinded trials [11, 14–16]. Five trials used intercalated erlotinib plus chemotherapy as the drug delivery method, while other four trials used continuous erlotinib plus chemotherapy treatment. Three trials enrolled an Asian-dominant population [11, 13, 14]http://www.sciencedirect.com/science/article/pii/S1525730411002105 - bib22, while other six trials enrolled a Caucasian-dominant population [8–10, 12, 15, 16]. One trial only enrolled patients who never smoked [13]. Five studies compared gemcitabine based chemotherapy plus erlotinib versus gemcitabine based chemotherapy alone [8, 11, 12, 14, 15], two trials compared pemetrexed and erlotinib with either pemetrexed or erlotinib alone [9, 13], one trial compared erlotinib plus docetaxel versus erlotinib or docetaxel alone [10], and one assessed erlotinib plus paclitaxel based chemotherapy versus paclitaxel based chemotherapy alone [16]. One trial did not show HRs for PFS or OS [22], but later it was showed in another article [12]. In three studies, the EGFR mutation status was confirmed in 601 patients [11, 13, 16]. One of these three studies reported data for subgroup analysis according to mutation status [11], one reported them in another article [23], and one did not provide enough data [13]. The characteristics of eligible studies are summarized in Table 1.


Chemotherapy plus Erlotinib versus Chemotherapy Alone for Treating Advanced Non-Small Cell Lung Cancer: A Meta-Analysis.

Xu JL, Jin B, Ren ZH, Lou YQ, Zhou ZR, Yang QZ, Han BH - PLoS ONE (2015)

Flow Diagram of Included and Excluded Studies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493135&req=5

pone.0131278.g001: Flow Diagram of Included and Excluded Studies.
Mentions: A total of 1597 articles were identified by the initial search strategy. After excluding irrelevant studies, review articles, RCTs without adequate data, meta-analyses, observational studies, single arm trials and case reports, nine trials were finally included for this meta-analysis (S1 File shows a list of full-text excluded articles). The selection steps are summarized in the flow chart shown in Fig 1. These trials enrolled a total of 3599 patients. Among them [8–16], four trials were placebo-controlled double-blinded trials [11, 14–16]. Five trials used intercalated erlotinib plus chemotherapy as the drug delivery method, while other four trials used continuous erlotinib plus chemotherapy treatment. Three trials enrolled an Asian-dominant population [11, 13, 14]http://www.sciencedirect.com/science/article/pii/S1525730411002105 - bib22, while other six trials enrolled a Caucasian-dominant population [8–10, 12, 15, 16]. One trial only enrolled patients who never smoked [13]. Five studies compared gemcitabine based chemotherapy plus erlotinib versus gemcitabine based chemotherapy alone [8, 11, 12, 14, 15], two trials compared pemetrexed and erlotinib with either pemetrexed or erlotinib alone [9, 13], one trial compared erlotinib plus docetaxel versus erlotinib or docetaxel alone [10], and one assessed erlotinib plus paclitaxel based chemotherapy versus paclitaxel based chemotherapy alone [16]. One trial did not show HRs for PFS or OS [22], but later it was showed in another article [12]. In three studies, the EGFR mutation status was confirmed in 601 patients [11, 13, 16]. One of these three studies reported data for subgroup analysis according to mutation status [11], one reported them in another article [23], and one did not provide enough data [13]. The characteristics of eligible studies are summarized in Table 1.

Bottom Line: Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01).Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06).In addition, intercalated administration is an effective combinatorial strategy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.

ABSTRACT

Background: Whether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC.

Methods: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015).

Results: Nine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06).

Conclusion: Combination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation-positive disease. In addition, intercalated administration is an effective combinatorial strategy.

No MeSH data available.


Related in: MedlinePlus