From the Journals

Nivolumab yields long-term survival benefit in advanced NSCLC

View on the News

Survival greatly improved, commentators report.

Recent advances in the treatment of metastatic non–small cell lung cancer are largely attributable to the arrival of checkpoint inhibitor therapy. As the body of evidence continues to grow, the long-term survival advantages seen with these agents are becoming increasingly apparent.

The findings of a combined analysis of four trials evaluating second-line nivolumab in patients with non–small cell lung cancer were recently reported. In comparison with historical data, which estimated 5-year overall survival rates to be less than 5%, the 4-year overall survival of 14% found by Dr. Antonia and colleagues is significant. The results suggest a plateau in overall survival of approximately 15% for patients in this setting.

With respect to safety, recent findings confirm that patients maintained on checkpoint inhibitor therapy should be closely monitored for the complete duration of exposure. In contrast to chemotherapy, there has been no evidence suggesting cumulative toxicity is related to immunotherapy treatment.

One question that remains from the current study is the ideal duration of checkpoint inhibitor therapy for patients who achieve an objective response. In addition, whether therapy should be maintained until adverse events or disease progression are seen also remains unclear. Various trials are presently ongoing in an attempt to help answer these remaining questions.

Pierre-Jean Souquet, MD, is affiliated with the University Hospital of Lyon (France). Sébastien Couraud, MD, PhD, is affiliated with the Université de Lyon (France). The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Dohme, Merck, and Roche. These comments are adapted from their editorial (Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30508-X ).


 

FROM THE LANCET ONCOLOGY

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

Recommended Reading

Bevacizumab or pemetrexed, but not both, efficacious for NSCLC maintenance
MDedge Hematology and Oncology
Immune-related toxicities, hospitalization common with checkpoint inhibitor therapy
MDedge Hematology and Oncology
Bevacizumab-erlotinib combo falls short in EGFR-mutant advanced NSCLC
MDedge Hematology and Oncology
Center’s experience casts doubt on clinical utility of NGS
MDedge Hematology and Oncology
Survey: PCI use has declined in ES-SCLC
MDedge Hematology and Oncology
Rozlytrek approved for ROS1-positive metastatic NSCLC, cancers with NTRK gene fusion defects
MDedge Hematology and Oncology
Screening for pancreatic and lung cancers
MDedge Hematology and Oncology
EHR-derived data on tumor progression may predict survival
MDedge Hematology and Oncology
Adding chemo beats standard gefitinib for EGFR-mutated lung cancer
MDedge Hematology and Oncology
Local treatment boosts survival for some with oligometastatic lung cancer
MDedge Hematology and Oncology