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Role of Survival Post-Progression in Phase III Trials of Systemic Chemotherapy in Advanced Non-Small-Cell Lung Cancer: A Systematic Review.

BACKGROUND: In advanced non-small-cell lung cancer (NSCLC), with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP) has improved over the years and to what degree SPP correlates with overall survival (OS).

METHODS AND FINDINGS: Median progression-free survival (MPFS) time and median survival time (MST) were extracted in phase III trials of first-line chemotherapy for advanced NSCLC. SPP was pragmatically defined as the time interval of MST minus MPFS. The relationship between MPFS and MST was modeled in a linear function. We used the coefficient of determination (r(2)) to assess the correlation between them. Seventy trials with 145 chemotherapy arms were identified. Overall, median SPP was 4.7 months, and a steady improvement in SPP was observed over the 20 years (9.414-day increase per year; p<0.001) in parallel to the increase in MST (11.253-day increase per year; p<0.001); MPFS improved little (1.863-day increase per year). Overall, a stronger association was observed between MST and SPP (r(2) = 0.8917) than MST and MPFS time (r(2) = 0.2563), suggesting SPP and MPFS could account for 89% and 25% of the variation in MST, respectively. The association between MST and SPP became closer over the years (r(2) = 0.4428, 0.7242, and 0.9081 in 1988-1994, 1995-2001, and 2002-2007, respectively).

CONCLUSIONS: SPP has become more closely associated with OS, potentially because of intensive post-study treatments. Even in advanced NSCLC, a PFS advantage is unlikely to be associated with an OS advantage any longer due to this increasing impact of SPP on OS, and that the prolongation of SPP might limit the original role of OS for assessing true efficacy derived from early-line chemotherapy in future clinical trials.

Comparison of pemetrexed plus cisplatin with other first-line doublets in advanced non-small cell lung cancer (NSCLC): A combined analysis of three phase 3 trials.

In a first-line study of advanced NSCLC, pemetrexed-cisplatin was more effective among patients with adenocarcinoma and large-cell carcinoma compared with gemcitabine-cisplatin (median survival of 11.8 versus 10.4 months, P=.005), while survival with pemetrexed-cisplatin was shorter than with gemcitabine-cisplatin in patients with squamous cell carcinoma. The comparability of pemetrexed-cisplatin to other commonly used regimens within histology subgroups needs to be explored.

METHODS: This retrospective analysis combined the patient-level data from three phase 3 randomized controlled trials that compared the efficacy of different third generation platinum- and non-platinum based doublets. Unadjusted median survival times and Cox covariate-adjusted treatment hazard ratio (HR) estimates were calculated. Overall results and subgroups by histological type were reported.

RESULTS: This combined analysis consisted of 3467 patients. In the overall analysis, adjusted HRs favored pemetrexed (HR <1.0) to each of the other 5 regimens, though none of these HRs were statistically significant. Among patients with non-squamous histology, pemetrexed-cisplatin produced favorable HRs to each of the other regimens, achieving statistical significance when compared with vinorelbine-cisplatin (HR=0.67; 95% confidence intervals [CI]: 0.50, 0.91) and gemcitabine-cisplatin (HR=0.85; 95% CI: 0.75, 0.97). Among patients with squamous histology, 4 of the 5 comparison regimens produced favorable HRs (HR >1.0) when compared with pemetrexed-cisplatin, with only the comparison with gemcitabine-cisplatin achieving statistical significance (HR=1.23; 95% CI: 1.00, 1.51).

CONCLUSION: In the absence of randomized clinical trial data comparing pemetrexed-cisplatin to commonly used doublets in advanced NSCLC other than gemcitabine-cisplatin, this combined analysis of multiple trials provides estimates for such comparisons.

Resistance to EGFR targeting therapies in lung cancer.

The treatment of advanced non-small cell lung cancer (NSCLC) by therapies targeting the epidermal growth factor receptor (EGFR) pathway represents one of the most important advances in thoracic oncology. Reversible EGFR tyrosine kinase inhibitors (TKIs), like gefitinib and erlotinib, are able to achieve dramatic responses in a subset of patients.

However, most patients treated with TKIs eventually develop resistance against these drugs. Here we review the physiology and pathology of EGFR activation in NSCLC, the clinical experience with TKIs, the mechanisms of resistance against TKIs, and discuss various approaches to treat resistance against TKIs.

Survival Benefits from Follow-Up of Patients with Lung Cancer: A Systematic Review and Meta-Analysis

Introduction: The burden of lung cancer is high for patients and carers. Care after treatment may have the potential to impact on this. We reviewed the published literature on follow-up strategies intended to improve survival and quality of life.

Methods: We systematically reviewed studies comparing follow-up regimes in lung cancer. Primary outcomes were overall survival (comparing more intensive versus less intensive follow-up) and survival comparing symptomatic with asymptomatic recurrence. Quality of life was identified as a secondary outcome measure. Hazard ratios (HRs) and 95% confidence intervals from eligible studies were synthesized.

Results: Nine studies that examined the role of more intensive follow-up for patients with lung cancer were included (eight observational studies and one randomized controlled trial). The studies of curative resection included patients with non-small cell lung cancer Stages I to III disease, and studies of palliative treatment follow-up included limited and extensive stage patients with small cell lung cancer. A total of 1669 patients were included in the studies. Follow-up programs were heterogeneous and multifaceted. A nonsignificant trend for intensive follow-up to improve survival was identified, for the curative intent treatment subgroup (HR: 0.83; 95% confidence interval: 0.66–1.05). Asymptomatic recurrence was associated with increased survival, which was statistically significant HR: 0.61 (0.50–0.74) (p < 0.01); quality of life was only assessed in one study.

Conclusions: This meta-analysis must be interpreted with caution due to the potential for bias in the included studies: observed benefit may be due to systematic differences in outcomes rather than intervention effects. Some benefit was noted from intensive follow-up strategies. More robust data, in the form of randomized controlled trials, are needed to confirm these findings as the review is based primarily on observational studies. Future research should also include patient-centered outcomes to investigate the impact of follow-up regimes on living with lung cancer and psychosocial well-being.

VTE common in hospitalized COPD patients

Approximately one in 100 patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease develops venous thromboembolism during their hospital stay, Spanish study data show.

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