Luis Paz-Ares, MD
The European Commission has approved nivolumab (Opdivo) for the treatment of patients with nonsquamous non–small cell lung cancer (NSCLC), regardless of PD-L1 levels, according to Bristol-Myers Squibb (BMS), the developer of the PD-1 inhibitor.
The approval is based on data from the phase III CheckMate-057 trial, in which second-line nivolumab reduced the risk of death by 27% versus docetaxel in patients with nonsquamous NSCLC, including a 60% risk reduction among patients with the highest levels of PD-L1 expression.
Nivolumab was previously approved in Europe for the second-line treatment of NCSLC patients with squamous cell carcinoma.
“Today’s approval expands the availability of Opdivo as a treatment option for a broader range of lung cancer patients—previously treated metastatic squamous and now nonsquamous non–small cell lung cancer—which represents the majority of diagnosed lung cancer cases,” Luis Paz-Ares, MD, Hospital Universitario Doce de Octubre, in Madrid, Spain, said in statement.
“As the only approved PD-1 inhibitor proven to have demonstrated a survival benefit versus a standard of care, regardless of PD-L1 expression, healthcare providers can offer treatment with Opdivo to appropriate patients who have received prior chemotherapy without the need to first conduct biomarker testing to determine PD-L1 expression. This approval is meaningful news for patients and their families who are in need of new treatment options.”
The phase III open-label CheckMate-057 trial randomized 582 patients with advanced nonsquamous NSCLC after the failure of platinum-based doublet chemotherapy to nivolumab at 3 mg/kg IV every 2 weeks (n = 292) or docetaxel at 75 mg/m2
IV every 3 weeks (n = 290). The treatments were administered until disease progression or unacceptable toxicity.
Patients received a median of 6 and 4 doses in the nivolumab and docetaxel arms, respectively. The median patient age was 61 years in the nivolumab arm and 64 years in the docetaxel cohort, and all patients had an ECOG performance status of 0 or 1.
Prior maintenance with bevacizumab (Avastin), pemetrexed (Alimta), or erlotinib (Tarceva) was allowed, as was TKI therapy for known EGFR
mutations or ALK
translocation. Forty-percent and 38% of patients in the nivolumab and docetaxel arms, respectively, had received prior maintenance therapy. In the nivolumab arm, 15% of patients were EGFR-positive and 4% were ALK-positive, with comparable rates of 13% and 3%, respectively, in the docetaxel group.
Overall survival (OS) was the primary endpoint, with secondary objectives focused on progression-free survival (PFS), objective response rate (ORR) per RECIST v1.1, efficacy by PD-L1 expression, and safety.
The study was stopped early after an independent monitoring panel determined the primary endpoint of improved OS had been reached. Eligible patients were allowed to continue treatment or cross over to the nivolumab arm in an open-label extension of the study.
Data from an interim analysis presented at the 2015 ASCO Annual Meeting showed a median OS of 12.2 months with nivolumab versus 9.4 months with docetaxel (HR, 0.73; 96% CI, 0.59-0.89; P
= .0015), with a 1-year OS of 50.5% versus 39.0%, respectively.1
Updated long-term OS data for CheckMate-057 were recently presented at the 2015 European Cancer Congress2
and simultaneously published in The New England Journal of Medicine
. At a minimum follow-up of 17.2 months, the OS rate with nivolumab was 39% compared with 23% for docetaxel. There remained a 2.8-month OS benefit with nivolumab versus docetaxel (HR, 0.72; 95% CI, 0.60-0.88; P
ORR was 19% with the PD-1 inhibitor compared with 12% with chemotherapy (Odds Ratio = 1.72; 95% CI, 1.1-2.6; P
= .0246). Complete and partial response rates were 1% and 18% in the nivolumab arm and <1% and 12% in the docetaxel group, respectively. The stable disease rate was 25% and 42% with PD-1 inhibition and chemotherapy, respectively.
Median time to response was 2.1 months with nivolumab versus 2.6 months with docetaxel. Median duration of response was 17.2 months versus 5.6 months in the nivolumab and control arms, respectively. Fifty-two percent of the nivolumab responses are still ongoing compared with 14% of the docetaxel responses.
Median PFS was comparable between the cohorts at 2.3 months in the nivolumab arm compared with 4.2 months in the docetaxel group (HR, 0.92; 95% CI, 0.77-1.11; P
= .393). One-year PFS favored nivolumab at 18.5% versus 8.1% for the control arm.
The researchers measured PD-L1 levels in pretreatment tumor biopsies with the PD-L1 IHC 28-8 PharmDx test, which is now Conformité Européene (CE) marked in Europe and can be used by physicians to obtain additional clinical information.