Adding antiangiogenics to second-line treatment of NSCLC may improve survival

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Results from a meta-analysis suggest that adding anti-angiogenics to second-line treatment for non-small cell lung cancer (NSCLC) may improve survival outcomes, particularly in younger patients.

In the second-line (2LT) treatment of advanced non-small cell lung cancer (NSCLC), the addition of antiangiogenic (AA) drugs significantly prolongs overall survival (OS) and progression-free survival (PFS), according to the meta-analysis results Posted in European Journal of Cancer.

However, the benefit of this addition is clinically limited and is mainly observed in younger patients and after a shorter time from the start of first-line treatment, the authors cautioned, while the introduction of AA also significantly increased the risk of grade 3 or higher toxicities.

Previous research has shown that overexpression of vascular endothelial growth factor is associated with a poor prognosis of NSCLC; Angiogenic factors act to inhibit immune cells and induce immune suppression at multiple levels, the researchers explained.

Monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) have AA effects. Although several trials have investigated adding AA drugs to chemotherapy or other treatments like 2LT, the results have been inconsistent.

To further elucidate this practice as 2LT, the researchers conducted a meta-analysis of individual patient data using information from clinical trials completed before December 31, 2014. All trials compared AA plus the standard 2LT with the 2LT alone.

OS, defined as time from randomization to death from any cause or last follow-up, was the primary endpoint of the study, and PFS, defined as time from randomization and disease progression, death from any cause, or last follow-up served as a secondary endpoint.

Sixteen trials were included; of the 8629 patients, 64% had adenocarcinoma. More than half of the patients included had started a 2LT with AA drugs within 9 months of starting first-line treatment.

The analyzes revealed:

  • AA drugs significantly prolong OS (HR, 0.93; 95% CI, 0.89-0.98; P = 0.005) and PFS (HR, 0.80; 95% CI, 0.77-0.84; P
  • The absolute OS and PFS benefit at 1 year for AA was 1.8% and 3.5%, respectively
  • The OS benefit of AA drugs was greater in younger patients (HR, 0.87; 95% CI, 0.76-1.00; HR, 0.89; 95% CI, 0.81 -0.97; HR, 0.94; 95% CI, 0.87-1.02; HR, 1.04; 95% CI, 0.93-1.17) for patients younger than 50 years, 50 to 59 years, 60 to 69 years and at least 70 years, respectively (trend test: P = .02)
  • The benefit of OS from AA was greater in patients who started AA within 9 months of starting first-line therapy (RR = 0.88 [95% CI, 0.82-0.99]) than in patients who started AA later (HR = 0.99 [95% CI, 0.91-1.08]) (interaction: P= .03)

The results were similar for PFS. However, “this positive effect was significantly different between the 3 types of combinations (interaction test: P = .0004). The strongest effect was in the combination “mAb (or TKI) added to erlotinib (HR, 0.70; 95% CI, 0.63-0.77), whereas the effect of mAb or of TKI added to chemotherapy was HR=0.79 (95% CI, 0.73-0.86) and HR=0.85 (95% CI, 0.90-0.91), respectively,” wrote the authors.

Additionally, 66.2% of those who had AA plus 2LT had grade 3 or greater toxicity, compared to 55% with 2LT alone. AA drugs confer a higher risk of asthenia, neutropenia, hypertension and proteinuria, whereas their addition does not increase the risk of deep vein thrombosis, gastrointestinal bleeding, embolism or pulmonary hemorrhage or central nervous system ischemic events.

Overall, the data showed that adding AA medications to standard 2LT in people with advanced NSCLC reduced the risk of progression by 20% and death by 7%, regardless of subgroup. type of drug. However, these benefits need to be confirmed in clinical trials.

The potential heterogeneity among patients and the lack of analysis on specific subgroups of patients mark the limitations of meta-analysis. In addition, data on subsequent lines of treatment after the introduction of AA were not available in all trials.

“This meta-analysis clearly confirms that in the second-line setting of advanced NSCLC, the addition of AA [drugs] to the second standard treatment modestly but significantly prolongs the outcome,” the authors said.

“This benefit appears to be independent of AA drug type, but the observed benefit may be greater in younger patients and in patients with refractory tumors with a good and manageable safety profile,” they concluded.

Reference

Remon J, Lacas B, Herbst R, et al. Second-line lung cancer anti-angiogenic meta-analysis on individual patient data in non-small cell lung cancer: ANSELMA. Eur J Cancer. Published online March 11, 2022. doi:10.1016/j.ejca.2022.02.002

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