CHICAGO — Nivolumab conferred a 3-month median OS advantage in patients with non-squamous non–small cell lung cancer who progressed on platinum-based doublet chemotherapy compared with docetaxel chemotherapy, according to phase 3 study results presented at the ASCO Annual Meeting.
Patients with high levels of programmed cell death-1 (PD-L1) expression demonstrated the greatest benefit from nivolumab (Opdivo, Bristol-Myers Squibb), results showed.
Patients with non-squamous NSCLC who fail on platinum-based doublet chemotherapy have few other treatment options and poor OS outcomes, according to study background.
“Treatment opportunities are clearly needed [for lung cancer],” Luis Paz-Ares, MD, PhD, professor of medicine at Hospital Universitario 12 de Octubre in Madrid, Spain, said during a press conference. 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.”
Paz-Ares and colleagues assigned 582 patients with stage IIIB/IV non-squamous NSCLC 3 mg/kg nivolumab every 2 weeks (n = 292) or 75 mg/m2 docetaxel every 3 weeks (n = 290) until disease progression or unacceptable toxicity.
OS served as the primary endpoint. Secondary endpoints included objective response rate (ORR), PFS, efficacy by PD-L1 expression, quality of life, and safety.
Patients assigned nivolumab demonstrated a median OS of 12.2 months, whereas patients assigned docetaxel demonstrated a 9.4-month median OS. More patients assigned nivolumab achieved 1-year OS (50.5% vs. 39%). The HR for OS in favor of nivolumab was 0.73 (95% CI, 0.59-0.89).
The ORR was significantly higher in the nivolumab arm (19.2% vs. 12.4%; P = .0235), and the median duration of response was 17.2 months in the nivolumab arm vs. 5.6 months in the docetaxel arm.
However, nivolumab did not yield significantly improved PFS (2.3 months vs. 4.2 months; HR = 0.92; 95% CI, 0.77-1.11).
PD-L1 positivity at all cutoffs — which included 1%, 5% and 10% expression levels in tumor cells — was associated with benefit from nivolumab. Among patients with PD-L1 expression in 1% or more of tumor cells, those who received nivolumab demonstrated a median OS that exceeded 17 months, whereas patients who received docetaxel demonstrated a median OS of 9 months.
“The median survival of the nivolumab arm was unprecedented in this context, ranging from 17.2 months to 19.4 months” Paz-Ares said.
Patients with 10% or greater PD-L1 expression demonstrated the greatest OS benefit with nivolumab (HR = 0.4; 95% CI, 0.27-0.59).
Survival outcomes among PD-L1 negative patients did not differ between the treatment arms.
More patients assigned docetaxel experienced a grade 3 to grade 5 adverse event (53.7% vs. 10.5%) and discontinued treatment due to a drug-related adverse event (14.9% vs. 4.9%). One drug-related death occurred in the docetaxel cohort.
Nearly half of patients in each cohort (nivolumab, 42.1%; docetaxel, 49.7%) received subsequent systemic therapy after study drug discontinuation.
“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,” Paz-Ares said in a press release. “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.” — by Alexandra Todak
Paz-Ares LG, et al. Abstract LBA109. Presented at: ASCO Annual Meeting. May 29-June 2, 2015; Chicago.
Disclosure: The study was funded by Bristol-Myers Squibb. Paz-Ares reports honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Lilly, Pfizer, Merck and Roche/Genentech. Please see the study for a full list of all other researchers’ relevant financial disclosures.