Opdivo-Chemo Combo Before Surgery Improves Long-Term Lung Cancer Survival, Pivotal Trial Finds

Adding Opdivo (nivolumab) to chemotherapy before surgery significantly improves long-term overall survival compared to chemotherapy alone in patients with operable non-small cell lung cancer (NSCLC), according to a five-year analysis of a phase 3 trial. The results were published June 2 in The New England Journal of Medicineand presented at the annual meeting of the American Society of Clinical Oncology (ASCO). The research, led by Patrick M. Forde, Ph.D., was conducted by clinicians at the Johns Hopkins Kimmel Cancer Center and colleagues across the US and around the world.

NSCLC remains the leading cause of cancer deaths globally. About one in four patients with NSCLC have tumors that can be surgically removed, offering a chance for cure. But even after surgery, 30 to 55% of patients experience cancer recurrence and ultimately die from the disease. Although adding medications before surgery — known as neoadjuvant treatment — has shown promise, questions have remained about how much it helps in the long run.

Earlier results from the CheckMate 816 trial showed that combining Opdivo (nivolumab) with chemotherapy before surgery led to better tumor response and longer time without disease recurrence compared with chemotherapy alone. These benefits were seen across most patient groups, especially among those with stage IIIA disease, who made up the majority of the study population and typically have a poorer prognosis. While earlier data suggested a possible survival advantage with the combination treatment, longer follow-up was needed for confirmation, which is now provided by the 5-year analysis.

A total of 358 patients took part in the phase 3, randomized, open-label trial conducted across multiple countries. Participants were randomly assigned to receive either Opdivo plus platinum-based chemotherapy, or platinum-based chemotherapy alone. Treatments were given every three weeks for three cycles. Surgery was scheduled within six weeks after the final dose of neoadjuvant therapy. After surgery, patients could receive additional treatment such as chemotherapy, radiation, or both.

After a median follow-up of about 68 months, two-thirds (65.4%) of patients in the Opdivo group were alive at five years compared with 55% in the chemotherapy group. No new safety concerns were reported.

These findings mark the first time a neoadjuvant immunotherapy regimen has demonstrated a statistically significant survival benefit in a randomized phase 3 trial of any solid tumor.

“Just three doses of immunotherapy and chemotherapy showing a survival advantage is a big step forward for patients,” said Julie Brahmer, M.D., director of thoracic oncology at the Kimmel Cancer Center, in a news release.

In the group that received immunotherapy plus chemotherapy, 24% of patients achieved complete remission, meaning no tumor was found in the lungs or lymph nodes at the time of surgery. Among those patients, the five-year overall survival rate was 95.3%, compared with 55.7% in patients who did not achieve complete remission. In exploratory analyses, patients whose circulating tumor DNA (ctDNA) was cleared before surgery had a five-year survival rate of 75%, while survival was 52.6% in those without ctDNA clearance. The updated analysis also showed sustained event-free survival benefit and a reduced incidence of disease recurrence, including distant metastases.

In their paper, the investigators noted that these long-term results support the use of pathological complete response and ctDNA clearance as potential surrogate markers for overall survival, although further research is needed to validate their routine clinical use. They also emphasized the need to identify more effective treatment options for patients who do not achieve a complete pathological response, who had a higher risk of cancer-related death.

The trial was supported by Bristol Myers Squibb and Ono Pharmaceutical Company Ltd.