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Nivolumab improves rate of 5-year OS for patients with advanced NSCLC
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Nivolumab led to a 5-year survival rate much higher than historical rates in patients with advanced non–small cell lung cancer, according to long-term survival data presented at the American Association for Cancer Research Annual Meeting.
Nivolumab (Opdivo, Bristol-Myers Squibb) was associated with minimal adverse events, results also showed.
“This study has the longest follow-up survival for an immune checkpoint inhibitor in non–small cell lung cancer,” Julie R. Brahmer, MD, MSc, director of the thoracic oncology program and associate professor of oncology at the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine, said during a press conference.
Prior to the use of immunotherapies, 5-year survival was approximately 1% for patients with NSCLC, and therapy was limited. SEER data show 5-year survival for patients with NSCLC is 4.9%.
Therefore, Brahmer and colleagues reported updated results after 5-year follow-up among patients from the CA209-003 trial. Previous data from the trial showed promising clinical activity, and nivolumab was subsequently approved based on data from other trials for the second-line treatment of advanced NSCLC. However, long-term survival and efficacy data are sparse.
The study included 129 heavily pretreated patients with advanced NSCLC who researchers randomly assigned to receive 1 mg/kg, 3 mg/kg or 10 mg/kg of nivolumab every 2 weeks in 8-week cycles for up to 2 years.
Long-term safety and tolerability served as the primary objective. Response rate and duration of response served as secondary objectives.
Updated Kaplan-Meier analysis from the current study showed a 5-year OS of 16% (95% CI, 10-23) among all patients. Five-year OS appeared similar among patients with squamous NSCLC and nonsquamous NSCLC (15%; 95% CI, 8-25).
Sixteen patients (9 men; median age, 61.5 years; range: 44-80) survived more than 5 years. Of these, 12 were current smokers at baseline. Twelve of the 16 survivors had a partial response, and two patients each had stable and progressive disease as best overall response to treatment with nivolumab. Two patients in the survivor group had unique mutations.
“The long-term survivors had diverse baseline characteristics,” Brahmer said. “We don’t expect patients with these mutations to do well with immunotherapy, so that was interesting.”
Among all treated patients, grade 3 and 4 adverse events appeared similar between the groups.
At 5 years, 12 patients were not assigned further therapy with nivolumab after having previously stopped, all of whom showed no evidence of progressive disease after stopping treatment.
Four patients received subsequent therapy, one of whom stopped therapy after 2 years and showed signed of progressive disease.
“He was then treated with nivolumab and had another response that lasted another year. Then his disease progressed again,” Brahmer said. Another patient who experienced local regression began and stopped therapy.
Brahmer provided another example of a 61-year old man diagnosed in 2008 with locally advanced disease.
“He progressed a year later while on chemotherapy, and then began nivolumab treatment in 2011,” Brahmer said. “[A few months later,] he landed a partial response. He went on to receive 2 years of nivolumab treatment, and at this time — 6 years after initiation — he remains live and well, without any sign of progressive disease.”
Patients in the trial received 2 years of therapy and will continue to receive standard of care indefinitely. Other trials are ongoing that investigate if the time of immunotherapy can be decreased.
“My personal feeling is I don’t think these patients need to be treated [with immunotherapy] indefinitely,” Brahmer said. “We want to be able to better personalize this therapy and know ... the best time to stop therapy.”
The initial results of the CA209-003 trial represent a “landmark” in the history of immunotherapy for cancer, according to Suzanne L. Topalian, MD, director of the melanoma program and associate director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine.
“It showed for the first time that immunotherapy could be used to treat common cancers, not just melanoma and kidney cancer,” Topalian, who was not involved with the study, said during the press conference. “This [study] is the longest follow-up to date on patients with lung cancer. It should be noted that the 5-year OS really quadrupled the survival we would otherwise expect if the same patients received chemotherapy.” – by Melinda Stevens
Reference:
Brahmer JR, et al. Abstract CT077. Presented at: American Association for Cancer Research Annual Meeting; April 1-5, 2017; Washington, D.C.
Disclosure: The study was funded by Bristol-Myers Squibb. Brahmer reports research funding from and an advisor role with Bristol-Myers Squibb. Topalian reports research grants from Bristol-Myers Squibb.
Perspective
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Jorge Nieva, MD
Long-term survival for patients with advanced lung cancer has largely eluded oncologists since the advent of chemotherapy. The report from Brahmer and colleagues indicates that, at least for a subset of patients with advanced lung cancer, that goal has been achieved.
The researchers examined 129 patients who had been enrolled in a phase 1 study of nivolumab (Opdivo, Bristol-Myers Squibb). That study included patients with advanced or recurrent malignancies enrolled without regard to tumor PD-L1 status who researchers compared with SEER data. Researchers followed patients for a minimum of 58 months. The key finding is that 5-year OS was 16% among study patients compared with 4.9% in the reference SEER data for patients with non–small cell lung cancer.
For most oncologists, the goals of care for patients with advanced lung cancer focus on palliation and not cure. These findings — which show that long-term survival is not only possible, but available even to those patients who are heavily pretreated, without regard to smoking or PD-L1 status — should change the conversation to one that includes long-term survival as a goal of care. Similar analysis from early-phase clinical trials with other checkpoint inhibitors will be needed to confirm that the long-term survival findings are generalizable to other immuno-oncology therapeutics.
Focusing efforts on raising the height of the tail of the Kaplan-Meier survival plots for our patients with advanced NSCLC should be the new goal for oncologists, not merely improving the median survival statistic. Patients want to be cured, and 16% is not high enough. Identification of rational strategies with attention to combination and sequenced new agents should be the focus of thoracic oncologists and drug developers. However, single-agent treatment is already expensive, and combination therapy will be more so. In the report, no predictors prospectively identified the long-term survivors. Knowing which patients can be successfully treated with single-agent checkpoint inhibitors — as opposed to combinations — will deliver value health systems that struggle with the already high costs of these agents. However, for the 16% of patients who survived long term, the costs of therapy were certainly worth it.
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