At an 18-month analysis, the overall survival rate with the PD-1 inhibitor was 28 percent versus 13 percent with docetaxel in previously treated patients with squamous NSCLC.
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.
Findings from the CheckMate-063 study were similar to those from the larger CheckMate-017 trial. In this single-arm, open-label phase 2 study, 117 patients with squamous NSCLC received Opdivo at 3 mg/kg every two 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 percent. All-grade AEs occurred in 75 percent of patients in the trial. Grade 3/4 AEs were apparent in 17 percent of patients, including fatigue (4 percent), diarrhea (3 percent), and pneumonitis (3 percent).
“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, 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, the FDA granted Opdivo both a breakthrough therapy designation and a priority review for patients with previously treated nonsquamous NSCLC on September 2. Both designations were based on a 27 percent reduction in the risk of death with second-line Opdivo versus docetaxel in the phase 3 CheckMate-057 trial. Under this expedited review process, the FDA’s decision deadline is January 2, 2016.
Prior to lung cancer indications, the FDA for the treatment of patients approved Opdivo with unresectable or metastatic melanoma following treatment with Yervoy (ipilimumab) or a BRAF inhibitor. Numerous clinical trials continue to assess the medication across clinical indications.