Treatment with the immunotherapy Opdivo (nivolumab) reduced the risk of death by 32 percent compared with docetaxel for patients with previously treated squamous non–small cell lung cancer (NSCLC), according to an updated analysis of the phase 3 CheckMate-017 trial presented at the 2015 World Conference on Lung Cancer, a meeting of 7,000 oncology professionals.1
At an 18-month analysis, the overall survival (OS) rate with the PD-1 inhibitor was 28 percent versus 13 percent with docetaxel in previously treated patients with squamous NSCLC. The median OS with Opdivo was 9.2 versus 6.0 months for docetaxel. In a second study presented at the meeting, a similar 18-month OS rate of 27 percent was seen for pretreated patients with squamous NSCLC.2 In this smaller single-arm phase 2 trial, labeled CheckMate-063, the median OS was 8.1 months.
Based on an earlier assessment of these two trials, the FDA approved Opdivo 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 Opdivo 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, 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 3 open-label CheckMate-017 study, 272 pretreated patients with squamous NSCLC were randomized to receive Opdivo at 3 mg/kg every two weeks (135 patients) or docetaxel at 75 mg/m2 every three weeks (137 patients). The primary endpoint of the trial was OS. Secondary outcome measures included objective response rates, progression-free survival, safety and outcomes by PD-L1 expression.
At the 18-month analysis, the PFS rate with Opdivo was 17 percent versus 2.7 percent for docetaxel. The median PFS was 3.5 months with Opdivo compared with 2.8 months for docetaxel. The ORR with Opdivo was 20 percent versus 9 percent for docetaxel.
At the analysis, responses remained ongoing for 63 percent of patients treated with Opdivo. Additionally, to compensate for pseudoprogression, which is commonly seen with PD-1 inhibition, 28 patients continued to receive Opdivo after demonstrating classical signs of progression. Of these patients, nine displayed a non-conventional response (7 percent).
All-grade treatment-related adverse events (AEs) were less frequent with Opdivo (59 percent) compared with docetaxel (87 percent). Grade 3/4 AEs occurred in 8 percent of Opdivo-treated patients. Grade 5 AEs were not reported with Opdivo. Grade 3-5 AEs occurred in 58 percent of patients treated with docetaxel, which included 3 grade 5 events.