Suresh S. Ramalingam, MD
Treatment with the PD-1 inhibitor nivolumab (Opdivo) reduced the risk of death by 32% compared with docetaxel for patients with previously treated squamous non–small cell lung cancer (NSCLC), according to an updated analysis of the phase III CheckMate-017 trial presented at the 2015 World Conference on Lung Cancer.1
At an 18-month analysis, the overall survival (OS) rate with nivolumab was 28% versus 13% with docetaxel in previously treated patients with squamous NSCLC. The median OS with nivolumab was 9.2 versus 6.0 months for docetaxel (HR, 0.62; 95% CI, 0.48-0.81; P
= .0004). In a second study presented at the meeting, a similar 18-month OS rate of 27% was seen for pretreated patients with squamous NSCLC.2
In this smaller single-arm phase II trial, labeled CheckMate-063, the median OS was 8.1 months (95% CI, 6.1-10.9).
Based on an earlier assessment of these two trials, the FDA approved nivolumab in March 2015 as a treatment for patients with metastatic squamous NSCLC following a platinum-based chemotherapy. Additionally, the two studies were pivotal in the approval of nivolumab for patients with squamous NSCLC in Europe.
“Immuno-oncology agents like Opdivo provide a novel approach to treating cancer. The improvement in survival observed in advanced squamous non-small cell lung cancer represents an important step forward for our patients,” senior author of the CheckMate-063 study Suresh S. Ramalingam, MD, director, Division of Medical Oncology, Winship Cancer Institute of Emory University, said in a statement. “These updated results demonstrate the ability to achieve longer term survival outcomes in this patient population. In fact, the Kaplan-Meier curve from this study suggests a prolonged survival benefit for a subset of patients.”
In the phase III open-label CheckMate-017 study, 272 pretreated patients with squamous NSCLC were randomized to receive nivolumab at 3 mg/kg every 2 weeks (n = 135) or docetaxel at 75 mg/m2
every 3 weeks (n = 137). The primary endpoint of the trial was OS. Secondary outcome measures included objective response rates (ORR; RECIST v1.1), progression-free survival (PFS), safety, and outcomes by PD-L1 expression.
At the 18-month analysis, the PFS rate with nivolumab was 17% versus 2.7% for docetaxel. The median PFS was 3.5 months with nivolumab compared with 2.8 months for docetaxel (HR, 0.63; 95% CI, 0.48-0.83; P
= .0008). The ORR with nivolumab was 20% versus 9% for docetaxel (estimated odds ratio = 2.6; 95% CI, 1.3-5.5; P
At the analysis, responses remained ongoing for 63% of patients treated with nivolumab. Additionally, to compensate for pseudoprogression, which is commonly seen with PD-1 inhibition, 28 patients continued to receive nivolumab after demonstrating classical signs of progression. Of these patients, 9 displayed a non-conventional response (7%).
All-grade treatment-related adverse events (AEs) were less frequent with nivolumab (59%) compared with docetaxel (87%). Grade 3/4 AEs occurred in 8% of nivolumab-treated patients. Grade 5 AEs were not reported with nivolumab. Grade 3-5 AEs occurred in 58% of patients treated with docetaxel, which included 3 grade 5 events.
Findings from the CheckMate-063 study were similar to those from the larger CheckMate-017 trial. In this single-arm, open-label phase II study, 117 patients with squamous NSCLC received nivolumab at 3 mg/kg every 2 weeks until disease progression or treatment discontinuation. Patients had received prior treatment with a platinum-based therapy and at least one additional systemic regimen.
The 18-month confirmed ORR was 15% (95% CI, 9-22). All-grade AEs occurred in 75% of patients in the trial. Grade 3/4 AEs were apparent in 17% of patients, including fatigue (4%), diarrhea (3%), and pneumonitis (3%).
“Our approach to immuno-oncology research is intended to show meaningful improvement over the traditional standard of care on the benchmark endpoint of overall survival,” Michael Giordano, MD, senior vice president, head of Development, Oncology, Bristol-Myers Squibb, the company developing the drug, said in a statement. “With the data presented today, we remain confident in our immuno-oncology strategy, including fulfilling our goal in showing the survival benefit for Opdivo, not only in non-small cell lung cancer, but similar to the data already observed in advanced melanoma and other tumor types.”
In addition the squamous NSCLC approval, on September 2, 2015, the FDA granted nivolumab both a breakthrough therapy designation and a priority review for patients with previously treated nonsquamous NSCLC. Both designations were based on a 27% reduction in the risk of death with second-line nivolumab versus docetaxel in the phase III CheckMate-057 trial. Under this expedited review process, the FDA’s decision deadline is January 2, 2016.