Using Angiogenesis Inhibitors With EGFR-TKIs in NSCLC Has Limited Survival Benefit

Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations had longer progression-free survival (PFS) but did not significantly improve their overall survival (OS) using angiogenesis inhibitors and EGFR-tyrosine kinase inhibitors (TKIs) concurrently vs EGFR-TKIs alone. This was among the findings of a systematic review and meta-analysis published in BMC Pulmonary Medicine.

Researchers sought to compare the effects of EGFR-TKIs with angiogenesis inhibitors vs EGFR-TKIs alone in EGFR-mutated NSCLC through a meta-analysis of existing research. The reviewers searched for studies of patients with biopsy-confirmed NSCLC that assessed the efficacy of combining EGFR-TKIs with angiogenesis inhibitors, with a primary endpoint of progression-free survival or overall survival (OS) as well as secondary endpoints.

Reviewers identified 9 randomized controlled trials with a combined total of 1821 participants. Patients with advanced EGFR-mutated NSCLC patients who received combined angiogenesis inhibitor therapy (n=911) had a statistically significant prolonged PFS compared with those who received EGFR-TKI monotherapy (n=910; hazard ratio [HR], 0.65; 95% CI, 0.59-0.73; P <.00001).

Similar results indicating longer PFS with combination therapy vs monotherapy were seen in patients with 19Del mutation (n=918; HR, 0.62; 95% CI, 0.53-0.73, P <.00001) and 21L858 mutation (n=803; HR, 0.64; 95% CI, 0.56-0.72; P <.00001).

With respect to overall survival, no statistically significant difference was identified between the combination therapy vs monotherapy groups (HR, 0.90; 95% CI, 0.76-1.06; P =.20).

Patients who received combined therapy vs monotherapy were more likely to experience adverse events (HR, 2.43; 95% CI, 2.02-2.92, P <.00001), including rash (P =.05), diarrhea (P =.003), proteinuria (P <.00001), and hypertension (P<.0001).

Study limitations include the limited number of included studies, lack of analysis of publication bias, and the differing stratification factors used in each study, which limited subgroup analysis.

“The combination of EGFR-TKIs and angiogenesis inhibitors prolonged PFS in patients with EGFR-mutant advanced NSCLC, but the OS and ORR benefit was not significant, and the risk of adverse events was higher, more pronounced with hypertension and proteinuria,” the study authors concluded. They added that subgroup analysis results indicated that combination therapy “was associated with better PFS in the smoking, liver metastasis, and no brain metastasis groups,” and may have a potential OS benefit for patients who smoke and who have liver or brain metastasis.