ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA.

Abstract

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.

• Authors: Jordi Remon, Benjamin Lacas, Roy Herbst, Martin Reck, Edward B Garon, Giorgio V Scagliotti, Rodryg Ramlau, Nasser Hanna, Johan Vansteenkiste, Kiyotaka Yoh, Harry J M Groen, John V Heymach, Sumithra J Mandrekar, Isamu Okamoto, Joel W Neal, Rebecca S Heist, David Planchard, Jean-Pierre Pignon, Benjamin Besse, ANSELMA collaborative group
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 166 Pg. 112-125 (05 2022) ISSN: 1879-0852 [Electronic] England
• PMID: 35286903 (Publication Type: Journal Article, Meta-Analysis, Review)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors

Topics

• Aged
• Angiogenesis Inhibitors (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Humans
• Lung Neoplasms (drug therapy)
• Progression-Free Survival