The European Commission has approved Nivolumab BMS ( Opdivo ) for the treatment of locally advanced or metastatic squamous ( SQ ) non-small cell lung cancer ( NSCLC ) after prior chemotherapy.
This approval marks the first major treatment advance in SQ NSCLC in more than a decade in the European Union ( EU ).
Nivolumab is also the first and only PD-1 immune checkpoint inhibitor to demonstrate overall survival in previously-treated metastatic SQ NSCLC.
Approval is based on the results of CheckMate -017 and -063. In the Phase III CheckMate -017 study, Nivolumab has demonstrated superior clinical benefit across all endpoints versus Docetaxel [ Taxotere ], the standard of care, regardless of PD-L1 ( programmed death ligand-1 ) expression status, including a 41% reduction in the risk of death, significantly superior overall surival rate of 42% versus 24% for Docetaxel at one-year and superior durable antitumor activity.
In the Phase II CheckMate -063 study, Nivolumab has shown an estimated 41% one-year survival rate and a median overall survival of 8.2 months.
The safety profile of Nivolumab is consistent with previously-reported trials, and in Checkmate -017, is also favorable compared to Docetaxel.
In Europe, incidence and mortality rates for lung cancer are on the rise, currently accounting for 20% of all cancer deaths. NSCLC is one of the most common types of the disease and accounts for approximately 85% of lung cancer cases.
SQ NSCLC accounts for approximately 25% to 30% of all lung cancers.
For patients with NSCLC, whose disease reoccurs or progresses despite chemotherapy, the treatment options are limited and the prognosis is poor, with a five-year survival rate of approximately 2%, globally.
The European Commission’s approval is based on data from two studies ( phase III CheckMate -017 and phase II CheckMate -063 ). Together, the trials investigated Nivolumab at a dose of 3 mg/kg every two weeks, which has been well-established across the phase III nivolumab clinical development program for various tumors.
CheckMate -017 is a phase III, open-label, randomized clinical trial that evaluated Nivolumab 3 mg/kg intravenously over 60 minutes every two weeks versus standard of care, Docetaxel 75 mg/m2 intravenously administered every three weeks in patients with advanced SQ NSCLC who had progressed during or after one prior Platinum doublet-based chemotherapy regimen.
The study’s primary endpoint was overall survival and secondary endpoints included progression-free survival and overall response rate ( ORR ).
The trial included patients regardless of their PD-L1 expression status.
Results from CheckMate -017 showed a 41% reduction in the risk of death with a one-year survival rate of 42% for Nivolumab ( 42.1% [ 95% CI: 33.7, 50.3 ] ) versus 24% ( 23.7% [ 95% CI: 16.9, 31.1 ] ) for Docetaxel ( hazard ratio, HR=0.59, 96.8% CI: 0.43, 0.81; p=0.0002 ).
Median overall survival was 9.2 months versus 6 months for Nivolumab and Docetaxel, respectively.
Nivolumab also demonstrated consistent, statistically significant and clinically meaningful improvements across secondary endpoints, ORR and progression-free survival, versus Docetaxel in patients with previously treated advanced SQ NSCLC.
Survival benefit was observed independent of PD-L1 expression across all pre-specified expression levels ( 1%, 5% and 10% ).
The safety profile of Nivolumab in CheckMate -017 was consistent with prior studies and favorable versus Docetaxel.
Treatment-related adverse events occurred less frequently with Nivolumab ( any grade, 58%; grade 3-4, 6.9%; no grade 5 events ) than Docetaxel ( any grade, 86%; grade 3-5, 55%; grade 5, 2.3% ), including both hematology and non-hematology toxicities. Treatment-related adverse effects led to discontinuation in 3.1% of patients in the Nivolumab arm compared to 10.1% for Docetaxel.
Pneumonitis ( 1.5% ) was the most common treatment-related adverse effect leading to discontinuation in the Nivolumab arm and peripheral neuropathy ( 3.1% ) for the Docetaxel arm.
CheckMate -063 is a phase II, single-arm, open-label trial that included patients with metastatic SQ NSCLC who had progressed after two or more lines of therapy.
In this trial, the confirmed objective response rate by an independent radiology review committee, the study’s primary endpoint, was 14.5% ( 95% CI: 8.47, 22.2 ) with an estimated one-year survival rate of 41% and median overall survival of 8.21 months ( 95% CI: 6.05, 10.9 ).
The safety profile of Nivolumab in CheckMate -063 was consistent with prior clinical studies and managed using established treatment algorithms. ( Xagena )
Source: BMS, 2015