Low baseline endoglin levels suggest trend toward better survival with nintedanib in MPM
Low baseline levels of the biomarker endoglin may signal improved progression-free survival (PFS) and/or overall survival (OS) in chemotherapy-naïve patients with unresectable epithelioid malignant pleural mesothelioma (MPM) who received the triple angiokinase inhibitor nintedanib in addition to a doublet combination regimen comprising pemetrexed and cisplatin, according to results from the LUME Meso* trial presented at ELCC 2018.
Data from 77 chemotherapy-naïve MPM patients were obtained to determine potential biomarker associations with the treatment outcome. Of these, 71 had data for plasma angiogenic factors while 67 had genomic data available for biomarker analysis. Participants were receiving either nintedanib 200 mg twice daily or placebo for up to 6 cycles in conjunction with pemetrexed/cisplatin, followed by maintenance therapy with nintedanib or placebo, respectively. [ELCC 2018, abstract 213O]
Among the evaluated angiogenic factors, greater PFS and OS benefit was observed in participants with low baseline plasma levels of endoglin.
A potential PFS benefit was also associated with the VEGFR**1 SNP*** rs9582036 A/A genotype, while a weak OS effect was observed with major homozygous genotypes for the VEGFR3 SNPs rs307821 G/G and rs307826 A/A.
These findings supplement the study’s initial results showing improved PFS (median, 9.4 vs 5.7 months, hazard ratio [HR], 0.54, 95 percent confidence interval [CI], 0.33–0.87; p=0.010) and a trend for improved OS (median, 18.3 vs 14.2 months, HR, 0.77, 95 percent CI, 0.46–1.29; p=0.319) with nintedanib vs placebo.
The researchers underlined that all biomarker treatment associations could have been limited by the small subgroup population especially for the minor genotypes, as well as the nonsignificant FDR#-adjusted interaction tests.
Despite the small sample size and the lack of clear association between biomarkers and treatment benefit, the potential survival benefit represents the first biomarker effects for nintedanib-treated patients with MPM, said the researchers.
Although pemetrexed/cisplatin has been established as the standard first-line treatment for unresectable MPM, improvements in first-line treatment alternatives are warranted, given the aggressive nature of MPM. [Clin Lung Cancer 2017;18:589-593]
Nintedanib targets multiple signalling pathways associated with the pathogenesis of MPM, including VEGFR, noted the researchers. Given the favourable survival outcomes associated with the anti-VEGF agent bevacizumab combined with pemetrexed/cisplatin, the current findings further elucidate the potential of VEGF pathway inhibition as a suitable treatment approach for MPM, they added. [Lancet 2016;387:1405-1414]