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Isolating the Role of Bevacizumab in Elderly Patients With Previously Untreated Nonsquamous Non – Small Cell Lung Cancer

View Article: PubMed Central - PubMed

ABSTRACT

Patient-level data from 2 phase III studies in patients with previously untreated, advanced-stage, nonsquamous non–small cell lung cancer (NSCLC) were pooled to examine outcomes with bevacizumab and chemotherapy based on age.

Methods:: Data from patients randomized to paclitaxel–carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 (E4599) and PointBreak studies were pooled and compared with E4599 patients randomized to PC alone. Patients were grouped by age: below 65, 65 to 74, 70 to 74, below 75, and 75 years or above. A multivariable model was used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using time-to-event outcomes. Adverse events (AEs) were assessed by age group in each study.

Results:: The PC+bevacizumab and PC arms comprised 901 and 444 patients, respectively. PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.89), 65 to 74 years (HR, 0.80; 95% CI, 0.64-1.00), 70 to 74 years (HR, 0.68; 95% CI, 0.48-0.96), and below 75 years (HR, 0.78; 95% CI, 0.68-0.89) but not in those aged 75 years or above (HR, 1.05; 95% CI, 0.70-1.57). Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years (63% vs. 48%; P<0.05) and 75 years or above (81% vs. 56%; P <0.05) in E4599.

Conclusions:: This analysis suggests that the survival benefits associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC; no benefit, however, was observed for bevacizumab-eligible patients who were 75 years or above.

No MeSH data available.


Forest plots of overall survival (OS) (A and B) and progression-free survival (PFS) (C and D) for patients treated with paclitaxel–carboplatin+bevacizumab versus paclitaxel–carboplatin alone, by age subgroup. CI indicates confidence interval; HR, hazard ratio.
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Figure 1: Forest plots of overall survival (OS) (A and B) and progression-free survival (PFS) (C and D) for patients treated with paclitaxel–carboplatin+bevacizumab versus paclitaxel–carboplatin alone, by age subgroup. CI indicates confidence interval; HR, hazard ratio.

Mentions: The use of bevacizumab was associated with a significant reduction in the risk of death for patients aged below 65 years (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.89), 65 to 74 years (HR, 0.80; 95% CI, 0.64-1.00), 70 to 74 years (HR, 0.68; 95% CI, 0.48-0.96), and below 75 years (HR, 0.78; 95% CI, 0.68-0.89) in the pooled population (Fig. 1A). Among the 157 patients aged 75 years or above, the difference in OS was not statistically significant between treatment arms (HR, 1.05; 95% CI, 0.70-1.57). A similar pattern of OS benefit with PC+bevacizumab compared with PC alone was seen across age subgroups when comparing outcomes exclusively in the E4599 trial (Fig. 1B). The unadjusted Kaplan-Meier estimates for OS in the pooled analysis are shown for patients aged below 75 years and 75 years or above in Figure 2.


Isolating the Role of Bevacizumab in Elderly Patients With Previously Untreated Nonsquamous Non – Small Cell Lung Cancer
Forest plots of overall survival (OS) (A and B) and progression-free survival (PFS) (C and D) for patients treated with paclitaxel–carboplatin+bevacizumab versus paclitaxel–carboplatin alone, by age subgroup. CI indicates confidence interval; HR, hazard ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5016219&req=5

Figure 1: Forest plots of overall survival (OS) (A and B) and progression-free survival (PFS) (C and D) for patients treated with paclitaxel–carboplatin+bevacizumab versus paclitaxel–carboplatin alone, by age subgroup. CI indicates confidence interval; HR, hazard ratio.
Mentions: The use of bevacizumab was associated with a significant reduction in the risk of death for patients aged below 65 years (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.89), 65 to 74 years (HR, 0.80; 95% CI, 0.64-1.00), 70 to 74 years (HR, 0.68; 95% CI, 0.48-0.96), and below 75 years (HR, 0.78; 95% CI, 0.68-0.89) in the pooled population (Fig. 1A). Among the 157 patients aged 75 years or above, the difference in OS was not statistically significant between treatment arms (HR, 1.05; 95% CI, 0.70-1.57). A similar pattern of OS benefit with PC+bevacizumab compared with PC alone was seen across age subgroups when comparing outcomes exclusively in the E4599 trial (Fig. 1B). The unadjusted Kaplan-Meier estimates for OS in the pooled analysis are shown for patients aged below 75 years and 75 years or above in Figure 2.

View Article: PubMed Central - PubMed

ABSTRACT

Patient-level data from 2 phase III studies in patients with previously untreated, advanced-stage, nonsquamous non–small cell lung cancer (NSCLC) were pooled to examine outcomes with bevacizumab and chemotherapy based on age.

Methods:: Data from patients randomized to paclitaxel–carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 (E4599) and PointBreak studies were pooled and compared with E4599 patients randomized to PC alone. Patients were grouped by age: below 65, 65 to 74, 70 to 74, below 75, and 75 years or above. A multivariable model was used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using time-to-event outcomes. Adverse events (AEs) were assessed by age group in each study.

Results:: The PC+bevacizumab and PC arms comprised 901 and 444 patients, respectively. PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.89), 65 to 74 years (HR, 0.80; 95% CI, 0.64-1.00), 70 to 74 years (HR, 0.68; 95% CI, 0.48-0.96), and below 75 years (HR, 0.78; 95% CI, 0.68-0.89) but not in those aged 75 years or above (HR, 1.05; 95% CI, 0.70-1.57). Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years (63% vs. 48%; P<0.05) and 75 years or above (81% vs. 56%; P <0.05) in E4599.

Conclusions:: This analysis suggests that the survival benefits associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC; no benefit, however, was observed for bevacizumab-eligible patients who were 75 years or above.

No MeSH data available.