Patients with advanced non-squamous type non-small cell lung cancer (NSCLC) benefit from nivolumab after failed platinum-containing chemotherapy. This is the conclusion of the CheckMate 057 study. The tested substance was superior to docetaxel not only in terms of efficacy but also in terms of safety.
The results of the phase III CheckMate 057 trial were awaited with great interest, as current therapeutic options for patients no longer responding to platinum-containing chemotherapy and a tyrosine kinase inhibitor are limited and provide only minimal improvements in overall survival. This is precisely the population that could benefit from immunotherapy with nivolumab, a checkpoint inhibitor that increases T-cell activity and stimulates the body’s immune response. In CheckMate 057, 292 patients received nivolumab 3 mg/kg every two weeks and 290 received docetaxel 75 mg/m2 every three weeks until progression or unsustainable toxicities. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate.
Mortality risk reduced by 27
1-year survival was 51% with nivolumab compared with 39% with docetaxel, reflected in a 27% risk reduction (HR=0.73; 96% CI 0.59-0.89; p=0.00155). The risk of progression reduced non-significantly by 8%. The response rate was significantly higher under the test compound: 19.2% vs. 12.4% (p=0.0235). The response also lasted much longer.
Tumor PD-1 ligand (PD-L1) expression was associated with nivolumab efficacy, meaning these patients showed greater benefit in all endpoints. By binding to the PD-1 receptor on activated T cells, nivolumab prevents natural ligands such as PD-L1 and PD-L2 from interacting with the receptor. When these ligands are overexpressed, they cause T cells to be limited in their activation and proliferation. Thus, expression of the ligand predicted treatment success with nivolumab to some degree in CheckMate 057. However, the authors emphasized that expression is not very suitable as a predictive factor, as some (albeit few) patients also responded well without this ligand.
Better safety profile
With nivolumab, grade 3-5 adverse events occurred in 10.5% of patients; no deaths occurred. On docetaxel, however, there was one drug-associated death and grade 3-5 adverse events in 53.7% of patients.
Complementing these promising results, another study showed that nivolumab also provided benefit in pretreated NSCLC patients with squamous cell carcinoma (CheckMate 017). Specifically, the risk of mortality was reduced here by a significant 41%, and progression-free survival and response rates were also significantly improved under the drug. In contrast, PD-L1 expression status had no relevance to any of the endpoints.
Overall, the data suggest that nivolumab should be preferred to docetaxel after failed platinum-containing therapy.
Source: ASCO Congress, May 29-June 2, 2015, Chicago.
InFo ONCOLOGY & HEMATOLOGY 2015; 3(7): 5.
