Nivolumab Improves Survival in Phase III NSCLC Study

Nivolumab (Opdivo) improved survival versus docetaxel in patients with pretreated squamous cell non—small cell lung cancer (NSCLC) in the phase III CheckMate-017 trial, according to Bristol-Myers Squibb (BMS), which manufactures the drug.

The study was stopped early after an independent monitoring panel determined the primary endpoint of improved overall survival (OS) with the anti—PD-1 agent had been reached. Eligible patients will now be allowed to continue treatment or cross over to the nivolumab arm in an open-label extension of CheckMate-017.

In a statement, BMS noted that this is the first time an anti—PD-1 immune checkpoint inhibitor has demonstrated a survival advantage in lung cancer.

The phase III open-label CheckMate-017 trial involved 272 previously treated patients with advanced or metastatic squamous cell NSCLC. Participants were randomized to the fully human IgG4 monoclonal antibody nivolumab at 3 mg/kg intravenously every 2 weeks or docetaxel at 75 mg/m² intravenously every 3 weeks.

Beyond the primary OS endpoint, secondary endpoints included progression-free survival and objective response rate (ORR).

BMS is working with the researchers on a timetable for publication and presentation of the study data.

Previously, data from the open-label, single-arm, phase II CheckMate-063 study of nivolumab in NSCLC were presented at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.

The study included 117 heavily pretreated patients with advanced squamous cell NSCLC. All patients had failed two or more systemic treatments and 65% of participants (n = 76) had previously failed three or more treatments. Seventy-six percent of patients were within 3 months of completion of their most recent therapy.

Nivolumab was administered at 3 mg/kg intravenously every 2 weeks until disease progression or treatment discontinuation.

At 11 months’ follow-up ORR, as assessed by an independent panel, was 15% (95% CI, 8.7-22.2), with a median duration of response that was not yet reached.

The estimated 1-year survival rate was 41% (95% CI, 31.6-49.7) and the median OS was 8.2 months (95% CI, 6.05-0.91).

An additional 26% of patients had stable disease for a median duration of 6 months (95% CI, 4.73-10.91), producing a disease control rate (ORR plus stable disease) of 41%. Responses were observed independent of PD-L1 status for patients with quantifiable PD-L1 expression.

“There are currently no effective treatment options for patients with refractory squamous cell lung cancer after their disease has progressed through two prior therapies. Historically, these patients have had ORRs of 2% to 8% and median overall survival of about 5 months, so even though we have not yet reached the median duration of response [in this study], the signs are very promising,” said lead author Suresh S. Ramalingam, MD, when he presented the data in Chicago.

Ramalingam, who is a professor and director of medical oncology at Winship Cancer Institute of Emory University, added that the 41% 1-year OS rate compares favorably with previously demonstrated 1-year survival rates of 5.5% to 18% for patients with third-line squamous cell NSCLC.

Adverse events (AEs) of all types and grades occurred in 74% of patients; however, 85% of patients were able to receive at least 90% of their planned dose intensity.

Grade 3/4 drug-related AEs were reported in 17% of patients. The most common (≥2%) grade 3/4 AEs were fatigue (4.3%), pneumonitis (3.4%), and diarrhea (2.6%).

Discontinuations due to drug-related AEs of any grade occurred in 12% of patients.

Two drug-related deaths (1 hypoxic pneumonia, 1 ischemic stroke) occurred in patients with multiple comorbidities and progressive disease.

In an interview with OncLive at the Chicago symposium, Vassiliki Papadimitrakopoulou, MD, a professor at MD Anderson Cancer Center, expressed her enthusiasm for the Checkmate-063 nivolumab NSCLC data.

“The study looking at nivolumab monotherapy for squamous NSCLC is quite unprecedented. It shows promise for a group of patients who are not able to be served by any existing therapies. And it gives us a signal where to focus our further studies in this important area.”

In December 2014, nivolumab was approved by the FDA for patients with unresectable or metastatic melanoma following treatment with ipilimumab (Yervoy) or a BRAF inhibitor.