Second-Line Treatments in Non-small Cell Lung Cancer A Systematic Review of Literature and Metaanalysis of Randomized Clinical Trials

City Hospital, Department of Oncology, Via Settembrini 2, Rimini 47900, Italy.
Chest (Impact Factor: 7.48). 02/2009; 135(6):1596-609. DOI: 10.1378/chest.08-1503
Source: PubMed


To assess the efficacy of second-line treatments in non-small cell lung cancer (NSCLC).
A systematic review of literature with metaanalysis of randomized clinical trials (RCTs) was independently performed by three authors. A primary analysis included all RCTs comparing any approach (chemotherapy or therapy with epidermal growth factor receptor [EGFR] inhibitors) with placebo; a secondary analysis included all RCTs comparing any treatment with docetaxel therapy every 3 weeks. The 1-year survival rate (SR) of the primary analysis was the primary outcome of the study; the 1-year SR of the secondary analysis, response rate (RR), and time to progression of primary and secondary analyses were the secondary end points.
Fourteen RCTs met the selection criteria. The outcomes of 2,627 and 5,952 patients were analyzed in the primary and secondary analysis, respectively. A significant heterogeneity was documented in the primary analysis for 1-year SR with odd ratio [OR] = 0.763 (p = 0.029). No heterogeneity was documented for RR in the primary analysis, with OR = 0.165 (p < 0.001). A modest heterogeneity was documented in the secondary analysis for 1-year SR and RR, with 1-year SR OR = 0.924 (p = 0.122) and RR OR = 1.069 (p = 0.643).
Second-line treatments in NSCLC seem to improve the main outcomes better than supportive care. Docetaxel administration every 3 weeks probably remains the "gold standard" because at present the data in literature are not enough to support a greater efficacy of other alternative options. Further trials are needed to identify a clinical and biological profile that could predict the response to treatments and a criterion to select the patients to be treated with chemotherapy or EGFR inhibitors.

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Available from: Emiliano Tamburini, Mar 25, 2015
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    • "Although chemotherapy for advanced lung cancer is known to improve survival and quality of life compared with symptomatic treatment, lung cancers usually still progress after chemotherapy and are often aggravated by treatment-related complications2,3. Second-line chemotherapy could be carried out by altering other regimens in patients who stop first-line chemotherapy, allowing a greater survival rate compared with patients given symptomatic treatment only4,5. However, extension of overall survival (OS) is not guaranteed for all patients; some patients suffer from reduced survival or are overwhelmed by side effects of chemotherapy. "
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    ABSTRACT: Background This study analyzed the negative prognostic factors in patients who received second-line chemotherapy for advanced inoperable non-small cell lung cancer (NSCLC). Methods We retrospectively reviewed the records of 137 patients with inoperable stage III-IV NSCLC who received second-line chemotherapy. The effects of clinical parameters on survival were analyzed and the hazard ratios (HR) for mortality were identified by a Cox regression analysis. Results Sex, age older than 65 years, smoking history, cell type, T-stage, best response to first-line chemotherapy and first-line chemotherapy regimen were significant negative predictors in univariate analysis. The multivariate analysis showed that patients older than 65 years (HR, 1.530; 95% confidence interval [CI], 1.020-2.297), advanced T stage (T4 vs. T1; HR, 2.273; 95% CI, 1.010-5.114) and non-responders who showed progression with first-line chemotherapy (HR, 1.530; 95% CI, 1.063-2.203) had higher HR for death. Conclusion The age factor, T stage and responsiveness to first-line chemotherapy were important factors in predicting the outcome of patients with advanced NSCLC who received second-line chemotherapy. The results may help to predict outcomes for these patients in the future.
    Tuberculosis and Respiratory Diseases 07/2014; 77(1):13-7. DOI:10.4046/trd.2014.77.1.13
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    • "Although there is some knowledge about lung cancer patients' QOL undergoing palliative treatment, it has to be kept in mind that most of the studies investigated established treatment options in terms of superiority concerning patients' QOL (Dancey et al, 2004; Gebbia et al, 2010; Thongprasert et al, 2011) in a clinical trial setting with a highly selected patient population. Furthermore, information about patients' QOL is mostly limited to one line of treatment (predominantly 1st (Belani et al, 2006; Gebbia et al, 2010) and 2nd line CT (Dancey et al, 2004; Tassinari et al, 2009)). "
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    ABSTRACT: Background: Most lung cancer patients are diagnosed at an advanced disease stage and predominantly receive palliative treatment, which increasingly consists of several chemotherapy lines. We report on patients' quality of life (QOL) to gain knowledge on QOL during and across multiple lines of chemotherapy. This includes patients with (neo)adjuvant therapy up to 3rd or above line palliative chemotherapy. Methods: Lung cancer patients receiving outpatient chemotherapy at the Kufstein County Hospital completed an electronic version of the EORTC QLQ-C30. Linear mixed models were used for statistical analysis. Results: One hundred and eighty seven patients were included in the study. Surprisingly, irrespective of the chemotherapy line patients reported stable QOL scores during treatment. None of the calculated monthly change rates attained clinical significance, referring to established guidelines that classify a small clinical meaningful change as 5 to 10 points. According to treatment line, 3rd or above line palliative chemotherapy was associated with the worst QOL scores, whereas patients undergoing (neo)adjuvant or 1st line palliative chemotherapy reported fairly comparable QOL. Conclusion: The essential finding of our study is that all QOL aspects of the EORTC QLQ-C30 questionnaire remained unchanged during each chemotherapy line in an unselected population of lung cancer patients. Between treatment lines pronounced differences were found, indicating that later palliative chemotherapy lines are associated with higher QOL impairments. These changes in QOL may not primarily be related to the treatment, but rather refer to impairments due to disease progression and may be partly due to a consequence of the prior therapies.
    British Journal of Cancer 10/2013; 109(9). DOI:10.1038/bjc.2013.585 · 4.84 Impact Factor
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    ABSTRACT: A not negligible proportion of NSCLC patients may be considered eligible for a third-line therapy with a palliative intent. Unfortunately, it is not uncommon to observe toxic side-effects with lack of efficacy. Aim of our study was to analyse clinical factors potentially influencing the global outcome of advanced NSCLC patients receiving third-line therapy. Patients with histologically proven inoperable (IIIB) or metastatic (IV) NSCLC, who received a second- and third-line treatment (either with EGFR-TKIs or chemotherapy), were eligible for our analysis. 143 patients received a second-line treatment after failing a first line cisplatin-based chemotherapy. 52 patients from this series were offered a third-line treatment. In the third-line setting, a better overall survival (months) was related to sex and to response to second-line. Globally, our findings seem to indicate that an improved overall survival in third-line is more strictly dependent on response to second-line, thus suggesting that when planning a third-line treatment, response to second-line should be considered as a relevant factor for the decision making process.
    Lung cancer (Amsterdam, Netherlands) 09/2009; 68(3):433-7. DOI:10.1016/j.lungcan.2009.07.008 · 3.96 Impact Factor
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