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ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer:
Jordi Remon1, Benjamin Lacas2, Roy Herbst3
1Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France.
Background:
Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT.
Methods:
Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible. Fixed-effect models were used to compute pooled hazard ratios (HRs) for overall survival (OS, main end-point), progression-free survival (PFS) and subgroup analyses.
Results:
Sixteen trials were available (8,629 patients, 64% adenocarcinoma). AA significantly prolonged OS (HR = 0.93 [95% confidence interval {CI}: 0.89; 0.98], p = 0.005) and PFS (0.80 [0.77; 0.84], p < 0.0001) compared with 2LT alone. Absolute 1-year OS and PFS benefit for AA were +1.8% [-0.4; +4.0] and +3.5% [+1.9; +5.1], respectively. The OS benefit of AA was higher in younger patients (HR = 0.87 [95% CI: 0.76; 1.00], 0.89 [0.81; 0.97], 0.94 [0.87; 1.02] and 1,04 [0.93; 1.17] for patients <50, 50-59, 60-69 and ≥ 70 years old, respectively; trend test: p = 0.02) and in patients who started AA within 9 months after starting the first-line therapy (0.88 [0.82; 0.99]) than in patients who started AA later (0.99 [0.91; 1.08]) (interaction: p = 0.03). Results were similar for PFS. AA increased the risk of hypertension (p < 0.0001), but not the risk of pulmonary thromboembolic events (p = 0.21).
Conclusions:
In the 2LT of advanced NSCLC, adding AA significantly prolongs OS and PFS, but the benefit is clinically limited, mainly observed in younger patients and after shorter time since the start of first-line therapy.
Insights
Adding antiangiogenics (AA) to second-line chemotherapy (CT) in advanced non-small cell lung cancer (NSCLC) improves survival, but benefits are modest and concentrated in younger patients. Further research is needed to optimize treatment strategies.
Area of Science:
- Oncology
- Clinical Trials
- Pharmacology
Background:
- First-line immunotherapy plus chemotherapy (CT) is standard for advanced non-small cell lung cancer (NSCLC).
- A need exists to evaluate antiangiogenics (AA) as second-line treatments (2LT) in advanced NSCLC.
- This meta-analysis validates the efficacy of AA combined with 2LT.
Purpose of the Study:
- To assess the efficacy of antiangiogenics (AA) plus standard second-line therapy (2LT) compared to 2LT alone in advanced non-small cell lung cancer (NSCLC).
- To validate the efficacy of these combinations as 2LT in advanced NSCLC.
Main Methods:
- Individual patient data meta-analysis of randomized trials comparing AA plus 2LT to 2LT alone.
- Trials included had to end accrual before 2015.
- Fixed-effect models were used to calculate pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS).
Main Results:
- Antiangiogenics (AA) significantly prolonged OS (HR=0.93) and PFS (HR=0.80) compared to 2LT alone.
- Absolute 1-year OS and PFS benefits for AA were +1.8% and +3.5%, respectively.
- OS benefit was greater in younger patients (<50 years) and those starting AA within 9 months of first-line therapy. AA increased hypertension risk but not thromboembolic events.
Conclusions:
- Adding antiangiogenics (AA) to second-line therapy (2LT) in advanced non-small cell lung cancer (NSCLC) significantly improves OS and PFS.
- The clinical benefit of AA is limited and primarily observed in younger patients and those treated earlier after first-line therapy.
- While AA improves survival outcomes, careful consideration of patient selection and potential side effects like hypertension is warranted.
