Neoadjuvant Nivolumab/Chemotherapy Achieves Promising Responses in Resectable NSCLC

The combination of nivolumab (Opdivo) plus chemotherapy induced a statistically significant improvement in pathologic complete response (pCR) as neoadjuvant treatment prior to surgery in patients with resectable non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 CheckMate-816 (NCT02998528) clinical trial, according to a press release from Bristol Myers Squibb.

CheckMate-816 is the first and only phase 3 study to demonstrate benefit with immune checkpoint inhibition therapy in combination with chemotherapy as neoadjuvant treatment in nonmetastatic NSCLC.

“Up to half of patients who undergo surgery for non-metastatic lung cancer will experience disease recurrence,” said Mark Awad, MD, PhD, clinical director, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, in a statement. “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 non-small cell lung cancer. We look forward to following patients in this trial of nivolumab plus chemotherapy as a new way of treating resectable non-small cell lung cancer, with the potential that an improvement in pathologic complete response will lead to extended event-free survival and, ultimately, overall survival.”

A significant number more of patients in the nivolumab arm demonstrated no evidence of cancer cells in resected tissue compared with those who were treated with chemotherapy alone.

A full evaluation will be conducted on the CheckMate-816 study, and investigators plan to present the full data at an upcoming medical meeting. Although no longer recruiting, the trial remains ongoing to assess the co-primary end point of event-free survival and other key secondary end points, which include overall survival, major pathological response, and time to death or distant metastases.

For the primary analysis, a total of 358 patients were randomized to receive either 360 mg of nivolumab plus histology-based platinum chemotherapy doublet every 3 weeks for up to 3 doses or a platinum-based chemotherapy doublet along every 3 weeks for up to 3 doses, followed by surgery. The chemotherapy agents used in this study include cisplatin, vinorelbine, gemcitabine, docetaxel, pemetrexed, carboplatin, and paclitaxel.

The randomized, open-label study aimed to compare the nivolumab regimen to chemotherapy alone in terms of safety and effectiveness as treatment of patients with resectable NSCLC. To be included in the study, patients had to have early-stage IB-IIIA operable NSCLC, lung function capacity capable of tolerating surgery, an ECOG performance status of 0 or 1, and available tissue of primary lung tumor. Patients were excluded from enrolling if they had a locally advanced, inoperable, or metastatic disease; active, known, or suspected autoimmune disease; or prior treatment with any drug targeting T cell co-stimulation pathways, such as immune checkpoint inhibitors.

“The CheckMate-816 results build on Bristol Myers Squibb’s heritage in the treatment of thoracic cancers, where Opdivo-based regimens have demonstrated superior overall survival in patients with metastatic non-small cell lung cancer and unresectable malignant pleural mesothelioma,” said Abderrahim Oukessou, MD, vice president, thoracic cancers development lead, Bristol Myers Squibb, in a statement. “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."

Nivolumab is a PD-1 immune checkpoint inhibitor designed to harness the body’s immune system to restore anti-tumor immune response. The agent has received regulatory approval in July 2014 for anywhere in the world and is currently approved in over 65 different countries, including the United States, European Union, Japan, and China.

In October 2015, the combination of nivolumab plus ipilimumab (Yervoy) was the first immunotherapy combination to receive regulatory approval for the treatment of patients with metastatic melanoma. The combination has since been approved in more than 50 countries, including the United States and European Union. Phase 3 studies have also demonstrated benefit with nivolumab-based regimens as treatment of patients with early-stage cancers, including lung, bladder, esophageal/gastroesophageal junction cancer, and melanoma.

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_{Opdvio (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/3lg1rIC}