Neoadjuvant Nivolumab/Chemo Combo Significantly Improves pCR in Resectable NSCLC

Mark Awad, MD, PhD

The combination of nivolumab (Opdivo) plus chemotherapy resulted in a statistically significant improvement in pathologic complete response (pCR) when used as neoadjuvant treatment in patients with resectable non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 CheckMate-816 trial (NCT02998528).¹

Results from the trial demonstrated that more patients who received nivolumab in combination with chemotherapy prior to surgery had no evidence of cancer cells in their resected tissue versus those who received chemotherapy alone. Additionally, the safety profile of the combination proved to be consistent with what has been observed in prior studies conducted in NSCLC.

Notably, this phase 3 trial is the first to show a benefit with an immune checkpoint inhibitor/chemotherapy combination as neoadjuvant treatment in patients with nonmetastatic NSCLC, according to Bristol Myers Squibb.

The company announced plans to complete a full assessment of the data from CheckMate-816 and will collaborate with investigators to present the findings at an upcoming medical meeting. Plans to discuss potential regulatory options with health authorities are also underway. The trial will continue to evaluate the other primary end point of event-free survival (EFS), along with other key secondary end points.

“Up to half of patients who undergo surgery for nonmetastatic lung cancer will experience disease recurrence,” Mark Awad, MD, PhD, clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, stated in a press release. “Nivolumab has shown benefit as an adjuvant, or post-surgical, treatment option in other cancer types, and the positive results from CheckMate-816 speak to its potential in the neoadjuvant setting of resectable NSCLC. We look forward to following patients in this trial of nivolumab plus chemotherapy as a new way of treating resectable NSCLC, with the potential that an improvement in pCR will lead to EFS and, ultimately, overall survival (OS).”

In the open-label, multicenter phase 3 trial, investigators set out to examine neoadjuvant nivolumab in combination with chemotherapy versus chemotherapy alone in patients with resectable NSCLC.

To be eligible for participation, patients had to have early stage IB-IIIA, operable NSCLC confirmed in the tissue, lung function capacity capable of tolerating the proposed lung surgery, an ECOG performance status of 0 t o1, and available tissue in the primary tumor.²

If patients had locally advanced, inoperable, or metastatic disease, they were excluded. Additionally, patients with active, known, or suspected autoimmune disease could not participate. Previous treatment with any drug designed to target T-cell co-stimulations pathways was not permitted.

For the primary analysis of the trial, a total of 358 patients were randomized to receive nivolumab at a dose of 360 mg in combination with histology-based, platinum-doublet chemotherapy every 3 weeks for up to 3 doses, or platinum-doublet chemotherapy every 3 weeks for up to 3 doses, followed by surgery.

The primary end points of the trial are pCR and EFS, while key secondary end points include OS, major pathologic response, and time to death or distant metastases.

“The CheckMate-816 results build on Bristol Myers Squibb’s heritage in the treatment of thoracic cancers, where [nivolumab]-based regimens have demonstrated superior OS in patients with metastatic NSCLC and unresectable malignant pleural mesothelioma,” Abderrahim Oukessou, MD, vice president and thoracic cancers development lead at Bristol Myers Squibb, added in the release. “In addition, these data add to our growing scientific understanding of the potential of immunotherapy approaches to transform outcomes in earlier stages of different cancer types, when the immune system may be more responsive.”

To date, nivolumab has been shown to be effective in both the neoadjuvant and adjuvant settings spanning 4 tumor types: lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer, and melanoma, according to Bristol Myers Squibb.

References:

1. Opdivo (nivolumab) plus chemotherapy shows statistically significant improvement in pathologic complete response as neoadjuvant treatment of resectable non-small cell lung cancer in phase 3 CheckMate -816 trial. News release. Bristol Myers Squibb. October 7, 2020. Accessed October 7, 2020. https://bit.ly/3iDKRAW.
2. A neoadjuvant study of nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy alone in early stage non-small cell lung cancer (NSCLC) (CheckMate 816). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02998528.