The European Commission has approved new indications for the immunotherapy nivolumab (Opdivo, Bristol-Myers Squibb), expanding its use in the treatment of non-small-cell lung cancer (NSCLC), and adding the indication of renal cell carcinoma (RCC).
The drug is already approved in Europe for use in previously treated patients with metastatic squamous NSCLC. Now the indication has been expanded to include non-squamous NSCLC, which represents 85% of the cases of lung cancer, and monotherapy in locally advanced or metastatic disease.
Nivolumab is the only PD-1 inhibitor that has been approved for a broad range of patients with previously treated metastatic NSCLC, regardless of PD-L1 expression, and nivolumab is the only approved PD-1 inhibitor to demonstrate a better overall survival rate than docetaxel in previously treated metastatic NSCLC, the manufacturer pointed out in a press release.
"As the only approved PD-1 inhibitor proven to have demonstrated a survival benefit, compared with a standard of care, regardless of PD-L1 expression, healthcare providers can offer treatment with nivolumab to appropriate patients who have received previous chemotherapy without the need to first conduct biomarker testing to determine PD-L1 expression," Luis Paz-Ares, MD, from Hospital Universitario Doce de Octubre in Madrid, said in the press release.
The approval is based on results from the phase 3 CheckMate-057 trial, an open-label randomized study that compared nivolumab with docetaxel in patients with metastatic non-squamous NSCLC.
Patients were randomized to receive nivolumab 3 mg/kg administered intravenously every 2 weeks or docetaxel 75 mg/m² administered intravenously every 3 weeks. A prespecified interim analysis was conducted when 413 events were observed (93% of the planned number of events for final analysis).
Nivolumab demonstrated better overall survival than docetaxel, with a 27% reduction in the risk for death (hazard ratio [HR], 0.73; P = .0015). The 1-year survival rate was 51% for nivolumab and 39% for docetaxel.
The median overall survival was 12.2 months with nivolumab and 9.4 months with docetaxel. The objective response rate was 19% with nivolumab (56/292; four complete responses, 52 partial responses) and 12% with docetaxel (36/290; one complete response, 35 partial responses; P = .0246).
The median duration of response was 17.2 months with nivolumab and 5.6 months with docetaxel, and median progression-free survival was 2.3 months and 4.2 months, respectively (HR, 0.92; P = .3932).
New Indication of Kidney Cancer
The European Commission has also granted approval for the use of nivolumab in adults with advanced RCC after previous therapy, making it the first and only PD-1 inhibitor with this indication.
This approval is based on results from the phase 3 CheckMate-025 study, which were presented last year and published simultaneously in the New England Journal of Medicine (2015;373:1803-181).
This trial compared nivolumab with everolimus in patients with advanced clear-cell RCC who had received previous antiangiogenic therapy. Patients treated with nivolumab achieved a median overall survival of 25.0 months, compared with 19.6 months with everolimus (HR, 0.73; 98.5% confidence interval, 0.57 - 0.93; P = .0018), representing a greater than 5 month improvement over a current standard of care.
"In addition to the clinical efficacy results, patients treated with nivolumab experienced an improvement in their health-related quality of life and had a significantly lower symptom burden throughout treatment, compared with patients receiving everolimus," trial investigator Bernard Escudier, MD, chair of the Genitourinary Oncology Committee, Institut Gustave Roussy, in Villejuif, France, said in a press release. "Combined, these data support the use of nivolumab in clinical practice and represent important progress toward establishing a new standard of care in Europe," he added.
The safety profile of nivolumab in CheckMate-025 was consistent with previous studies, according to the manufacturer. Serious adverse events occurred in 47% of patients receiving nivolumab. The most frequent serious adverse reactions reported in at least 2% of patients receiving nivolumab were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In the study, the most common adverse reactions (≥20%) reported in patients receiving nivolumab (vs everolimus) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%).
Both CheckMate studies were funded by Bristol-Myers Squibb, the manufacture of nivolumab
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