Promising data on a Phase III trial (NCT01673867) to assess the safety and efficacy of nivolumab in the treatment of non-squamous non-small cell lung cancer (NSCLC) was recently presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, May 29 to June 2. The abstract was presented by Dr. Luis Paz-Ares from Hospital Universitario Virgen Del Rocio in Spain and was entitled “Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC)” (Abstract No. LBA109).
NSCLC is the most common type of lung cancer, accounting for approximately 85% of all the lung cancers diagnosed. Patients with non-squamous NSCLC who fail to respond to standard platinum-based doublet chemotherapy only have a few therapeutic options, and usually have a poor overall survival outcome. “Treatment opportunities are clearly needed [for lung cancer],” noted Dr. Paz-Ares according to a news release. “In the context of patients with non-squamous NSCLC, when they have failed platinum-based chemotherapy, the typical response rate with available treatments and standard-of-care docetaxel is in the range of 10%, and expected survival is between 8 and 10 months.”
Nivolumab (Opdivo, Bristol-Myers Squibb) is an antibody against the programmed death 1 (PD-1) receptor, an immune checkpoint that if inhibited results in the stimulation of the body’s antitumor immunity.
This Phase III trial enrolled 582 non-squamous NSCLC patients who received 3 mg/kg nivolumab every 2 weeks (292 patients) or 75 mg/m2 standard-of-care docetaxel every 3 weeks (290 patients) until there were signs of disease progression or discontinuation due to issues like toxicity. The study’s primary endpoint was the overall survival, while the secondary endpoints included efficacy, safety, objective response rate (ORR) and quality of life.
Researchers found that NSCLC patients who received nivolumab had a median overall survival of 12.2 months, while patients given docetaxel treatment had a median survival of 9.4 months. In total, 50.5% of the patients under nivolumab treatment were found to achieve 1-year overall survival in comparison to 39% in the cohort of patients receiving docetaxel. The ORR was found to be significantly higher in the nivolumab group (19.2%) and with a longer median duration of response (17.2 months) in comparison to the docetaxel group (ORR of 12.4%; median duration of response of 5.6 months).
NSCLC patients with programmed cell death-1 (PD-L1, which binds to the PD-1 receptor) expression in 1% or more of the cancer cells had a median overall survival of 17.2 months in the nivolumab group and of 9 months in the docetaxel group. Patients with 10% or higher PD-L1 expression were found to have even greater benefit from treatment with nivolumab. “The median survival of the nivolumab arm was unprecedented in this context, ranging from 17.2 months to 19.4 months,” said Dr. Paz-Ares. Among PD-L1 negative patients, the survival rate did not differ between the two treatments.
Regarding adverse events, patients who received docetaxel experienced more severe events (53.7% vs 10.5%) and 14.9% had to discontinue treatment due to drug-related adverse effects (4.9% in the nivolumab group). One drug-related death was reported in the docetaxel cohort.
The team concluded that in patients with non-squamous NSCLC who have failed platinum-based chemotherapy, nivolumab is a safer treatment and offers a longer median overall survival rate in comparison to docetaxel chemotherapy.
“This is the first phase 3 study to show that immunotherapy is effective against non-squamous cell NSCLC and appears to be particularly active in patients with PD-L1 positive tumors,” concluded Dr. Paz-Ares. “While nivolumab appears to be more potent against this most common lung cancer, it is important to note that it is also far easier on patients compared to the standard second-line treatment, docetaxel.”