Nivolumab exceeds standard 5-year survival in NSCLC in CheckMate 003
Non-small cell lung cancer (NSCLC) patients treated with the immune checkpoint inhibitor nivolumab showed a 16 percent 5-year overall survival (OS) rate, according to long-term follow-up data of the CheckMate 003* study presented at the American Association for Cancer Research Annual Meeting 2017 (AACR 2017) held recently in Washington, DC, US.
“The 5-year overall survival rate reported in this study is much higher than what is reported for this population of patients receiving standard-of-care treatment,” according to Dr Julie Brahmer from Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, US. “Statistics show that most patients with advanced disease die within a year of diagnosis, and the [historical] 5-year survival rate for metastatic NSCLC is about 4 percent.”
The phase Ib dose-escalation expansion study randomized 129 advanced NSCLC patients, who were previously treated with one to five lines of systemic regimens, to receive nivolumab at either 1, 3, or 10 mg/kg Q2W in 8-week cycles for up to 96 weeks of treatment or until disease progression or intolerance to toxicity. They were followed for at least 58 months. [AACR 2017, abstract CT077]
The Kaplan-Meier analysis estimated the 5-year OS rate to be 16 percent (95 percent confidence interval [CI], 10–23) in the overall study population. Specifically, similar OS rates were seen in patients with squamous (n=54; 16 percent, 95 percent CI, 8–28) and nonsquamous (n=74; 15 percent, 95 percent CI, 8–25) NSCLC.
Of the 16 patients (median age 61.5 years, nine males) who survived for at least 5 years, 12 patients did not require further therapy after stopping nivolumab at 96 weeks and remained progression-free for at least 5 years.
“A small subset of NSCLC patients appear to respond to nivolumab and have beaten the odds that most patients with this cancer face,” said Brahmer. “Our study results show that for a small subset of patients, immunotherapy can work for a very long time.”
Sixty-eight patients whose tumour samples were available for PD-L1 staining showed varying survival rates with different PD-L1 expression levels: the estimated 5-year OS was 20 percent for those with <1 percent PD-L1 expression (n=30), 23 percent for those with ≥1 percent expression (n=38), and 43 percent among those with ≥50 percent PD-L1 expression (n=13).
“We saw improved survival across all PD-L1 staining,” said Brahmer, who attributed the nonsignificant difference between the three groups to the small patient number in each subgroup.
“It’s clear that the patients who beat the survival odds are in some ways truly unique biologically, and the goal now is to discover exactly how immunotherapy is keeping their disease in check,” said Brahmer.
Thus far, the researchers were unable to identify any factors linked to long-term survival within the 16 survivors, who did not appear to differ from the overall study population in terms of clinical, demographic, and biological features.
“Now, we need to figure out how to make more patients responsive to immunotherapy by exploring combinations of immunotherapy drugs and other treatment agents,” Brahmer suggested.