Treatment with nivolumab (Opdivo) was associated with a 5-year overall survival rate of 13.4% compared with 2.6% with docetaxel in patients with previously treated non–small cell lung cancer.
Scott Gettinger, MD
Treatment with nivolumab (Opdivo) was associated with a 5-year overall survival (OS) rate of 13.4% compared with 2.6% with docetaxel in patients with previously treated non—small cell lung cancer (NSCLC), according to long-term pooled efficacy and safety data from the phase III CheckMate-017 and CheckMate-057 trials that were presented at the 2019 World Conference on Lung Cancer (WCLC).1
The OS benefit with nivolumab was observed across all patient subgroups, including those with PD-L1 expression on <1% of tumor cells, stated Bristol-Myers Squibb (BMS), the developer of the PD-1 inhibitor, in a press release. Additionally, the safety profile for nivolumab was consistent with prior findings of the agent in the second-line setting, and no new safety signals were observed with the longer follow-up.
The pooled 5-year analysis is the longest follow-up reported from randomized phase III trials of a checkpoint inhibitor in this setting, the company stated.
“CheckMate-017 and -057 are the first phase III trials to report 5-year outcomes for a PD-1 inhibitor in previously treated advanced NSCLC, demonstrating a greater than five-fold increase in 5-year OS rates with nivolumab (13.4%) compared with docetaxel (2.6%). Nivolumab remained well tolerated with no new safety signals,” Scott Gettinger, MD, professor of internal medicine (medical oncology) at Yale Cancer Center, who presented the findings at the WCLC, stated in another press release.2
Historical outcomes for patients with advanced NSCLC have been poor, wit 5-year OS rates of <5% with standard chemotherapy.
Nivolumab was FDA approved in 2015 for the treatment of patients with metastatic NSCLC following progression on or after platinum-based chemotherapy. Patients with EGFR or ALK alterations should experience disease progression on a targeted therapy for these molecular abnormalities prior to receiving therapy with the PD-1 inhibitor.
The approval of nivolumab in this setting was based on earlier data from CheckMate-017 and CheckMate-057, both of which demonstrated an improved OS with nivolumab compared with docetaxel in this patient population. All patients had an ECOG performance status of 0 to 1.
The pooled analysis of the 2 randomized phase III CheckMate-017 and CheckMate-057 studies were designed to determine the long-term efficacy and safety of nivolumab in a larger population of patients (n = 854) with previously treated NSCLC across both squamous and nonsquamous histologies.
In both studies, patients who experienced disease progression during or after first-line platinum-based chemotherapy were randomized 1:1 to receive nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m2 once every 3 weeks until progression or unacceptable toxicity. After completion of the primary analysis, patients in the docetaxel arm who were no longer experiencing benefit from the treatment were permitted to cross over to receive nivolumab. The primary endpoint in both studies was OS.
At 5 years of follow-up, 50 patients on the nivolumab arm and 9 patients receiving docetaxel were alive. The baseline characteristics of the 5-year survivors in both arms were similar to the overall population as well as those who survived <1 year, except for a higher percentage of patients with an ECOG performance status of 0 or had PD-L1 expression <1% on nivolumab, and an ECOG performance status of 0 and stage IIIB NSCLC on docetaxel.
Results showed that among the patients who achieved an objective response to nivolumab, 32.2% of patients continued to have a response at 5 years compared with 0% of patients who received treatment with docetaxel. The median duration of response was 19.9 months and 5.6 months for the nivolumab and docetaxel arms, respectively. The 5-year progression-free survival rates were 8.0% with nivolumab compared with 0% for those who received docetaxel.
Between 3- and 5-years of follow-up, 8 of the 31 (26%) nivolumab-treated patients reported a treatment-related adverse event, one (3%) of which was of grade 3/4. The most common adverse event (AE) with a potential immunological cause—also known as a select AE—were related to skin, in 4 (13%) patients, none of which were of grade 3/4.
“Since the US Food and Drug Administration approval in second-line non—small cell lung cancer in 2015, Opdivo has become an important treatment option for this population of patients, who historically faced 5-year survival rates of less than 5% when treated with standard chemotherapy,” Sabine Maier, MD, development lead, Thoracic Cancers, BMS, stated in the press release. “The long-term survival outcomes from these two studies in a large patient population add to the body of evidence supporting the durability of Opdivo-based regimens, which has now been demonstrated across multiple tumor types and lines of therapy.”