As of November 30, 2015, nivolumab (Opdivo®) has been approved for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy (regardless of histological subtype). This takes into account the positive results from the two phase III studies CheckMate-057 and -017, which attracted attention at last year’s ASCO congress, among others.
Lung cancer incidence and mortality rates are increasing. In Switzerland, approximately 2460 men and 1440 women develop new cancer each year, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Limited treatment options and thus a particularly poor prognosis are faced by those NSCLC patients whose disease recurs or progresses despite chemotherapy. It is precisely this population that benefits from immunotherapy with the checkpoint inhibitor nivolumab. Specifically, nivolumab binds to the PD-1 checkpoint, which is used by cancer cells to override the cancer-specific immune response. By blocking PD-1, nivolumab activates the immune system or increases T-cell activity.
CheckMate-057 and -017
Two phase III studies were decisive for Swissmedic’s decision. In CheckMate-057, 292 pretreated patients with advanced nonsquamous-type NSCLC received nivolumab 3 mg/kg every two weeks and 290 docetaxel 75 mg/m2 every three weeks. In the primary endpoint, overall survival, there was a significant risk reduction of 27% with nivolumab (at one year: 51% vs. 39%; HR=0.73; 96% CI 0.59-0.89; p=0.00155). In addition, the response rate was significantly increased under the new compound and the overall safety profile was better than under docetaxel. The extended follow-up, which included presentations at ECCO/ESMO 2015, determined survival rates of 39% vs. 23% at 18 months.
Complementing this, CheckMate-017 showed that nivolumab also provided benefit in pretreated NSCLC patients with squamous cell carcinoma. The mortality risk here was reduced by a significant 41%. Progression-free survival and response rates were also significantly improved with the drug. Both studies were published in the New England Journal of Medicine [1,2].
Extension of indication likely
In addition to NSCLC, nivolumab is being intensively investigated in unresectable or metastatic melanoma. In several countries, including the EU, it is approved in this indication in the first or second line.
In the area of combining different immunotherapeutics, research is currently advancing strongly. It therefore remains to be seen which additional indications will be added in Switzerland in the future.
Source: Media release, December 3, 2015
Literature:
- Borghaei H, et al: Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015 Oct 22; 373(17): 1627-1639.
- Brahmer J, et al: Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015 Jul 9; 373(2): 123-135.
