Lung cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, causing nearly 2 million deaths a year. Although treatment advances in late-stage non–small lung cancer (NSCLC) are extending survival in some patients, breakthroughs for early-stage disease are just emerging.

The results from a 5-year follow-up analysis of a small clinical trial of patients with stage I to IIIA NSCLC who were treated with nivolumab for 4 weeks before surgery showed that the recurrence-free and overall survival rates were 60% and 80%, respectively. While major pathologic responses and PD-L1 positivity trended toward improved 5-year recurrence-free survival, definitive conclusions were limited by the small cohort size. Analysis from ongoing, larger-scale trials will be needed to definitively answer the questions raised in this study, according to the study abstract. The study by Samuel Rosner, MD, and colleagues was published in Clinical Cancer Research.

Samuel Rosner, MD

Study Methodology

Previously reported findings from a phase I/II clinical trial by the study authors in which patients with stage I to III resectable NSCLC were treated with two doses of neoadjuvant anti–PD-1 nivolumab showed that the treatment was safe and feasible, with encouraging major pathologic responses. In this final analysis from the trial, the researchers presented 5-year clinical outcomes, including 5-year recurrence-free and overall survival rates for the 20 patients who underwent surgical resection.

The patients received two preoperative doses of nivolumab at 3 mg/kg every 2 weeks. Surgical resection was planned approximately 4 weeks after the first dose.

Results

With a median follow-up of 63 months, 5-year recurrence-free survival and overall survival rates were 60% and 80%, respectively. The presence of major pathologic responses and pretreatment tumor PD-L1 positivity (TPS ≥ 1%) each trended toward favorable recurrence-free survival (hazard ratio (HR = 0.61, 95% confidence interval [CI] = 0.15–2.44 and HR = 0.36, 95% CI = 0.07–1.85, respectively). At 5-year follow-up, eight of nine (89%) patients with major pathologic response were alive and disease-free.

There were no cancer-related deaths among the patients with major pathologic response. In contrast, 6 of 11 patients without major pathologic response experienced tumor relapse, and 3 patients died.

“Five-year clinical outcomes for neoadjuvant nivolumab in resectable NSCLC compare favorably with historical outcomes. Major [pathologic] response and PD-L1 positivity trended toward improved recurrence-free survival, though definitive conclusions are limited by cohort size,” concluded the study authors.

Clinical Significance

“An interesting finding from the analysis was the difference in outcomes between patients with and without a major [pathologic] response,” said Dr. Rosner, co-first author of this study and a medical oncology fellow at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, in a public statement. “Although the sample size was small, the results illustrate the potential power of [pathologic] response as a predictive biomarker.”

Disclosure: Funding for this study was provided by Stand Up To Cancer, Bristol Myers Squibb, the International Immuno-Oncology Network, the LUNGevity Foundation, the International Association for the Study of Lung Cancer, the Prevent Cancer Foundation, the Lung Cancer Foundation of America, the MacMillan Foundation, the ECOG-ACRIN Cancer Research Group, the National Institutes of Health, Johns Hopkins University Cancer Center, and Memorial Sloan Kettering Cancer Center. For full disclosures of the study authors, visit aacrjournals.org/clincancerres.