Nivolumab Plus Chemotherapy Extends EFS in Non–Small Cell Lung Cancer

The CheckMate 816 trial, which is comparing the efficacy of neoadjuvant nivolumab (Opdivo) plus chemotherapy to chemotherapy alone in patients with resectable non-small cell lung cancer (NCSLC), has met its primary end point of event-free survival (EFS), according to a press release by Bristol Myers Squibb.¹ 

“While the intent of surgery is curative in resectable non-small cell lung cancer, between 30% to 55% of patients experience recurrence after surgery and ultimately succumb to the disease, presenting a strong need for additional options that can disrupt this cycle,” said Nicolas Girard, MD, PhD, professor of respiratory medicine at Paris Saclay University and head of the Thorax Institute Curie Montsouris in Paris, in a press release. “The positive event-free survival data seen with neoadjuvant nivolumab plus chemotherapy is groundbreaking and can have important implications for how we treat resectable non-small cell lung cancer.”

The CheckMate 816 trial (NCT02998528) has an estimated enrollment of 350 participants and an estimated study completion date of November 2028. The duel primary end points of the study are EFS up to 69 months, and pathological complete response at the time of surgery. Secondary end points include overall survival up to 193 months, major pathological response at the time of surgery, and time to death or distant metastases up to 69 months.²

During the study, patients were randomized into 1 of 3 arms. In arm 1, patients received platinum doublet chemotherapy. In arm 2, patients received nivolumab plus platinum doublet chemotherapy. In arm 3, patients received nivolumab plus ipilimumab (Yervoy).

In April, the study met its other primary end point of pathological complete response. In patients treated with the nivolumab/chemotherapy combination, the pathological complete response rate was 24%, compared with the 2.2% of patients treated with chemotherapy alone (OR 13.94, 99% CI, 3.49–55.75; P <.0001). Additionally, the major pathological response rate of patients in the nivolumab/chemotherapy arm was 36.9%, compared with the 8.9% of patients in the chemotherapy alone arm (OR, 5.70; 95% CI, 3.16-10.26).³

The combination was also found to not impede the feasibility and timing of surgery. Additionally, the combination of nivolumab and chemotherapy was found to deepen pathological response compared with chemotherapy monotherapy. In the nivolumab plus chemotherapy arm, the definitive surgery rate was 83% versus 75% in the chemotherapy alone arm. Additionally, the minimally invasive surgery rate was higher in the combination arm versus the monotherapy arm (30% vs 22%, respectively).⁴

In order to participate in the study, patients must have early stage IB-IIIA, operable NSCLC, lung capacity capable of tolerating the proposed lung surgery, an ECOG performance status of 0 or 1, and available tissue of primary lung tumor. Patients with locally advanced, inoperable or metastatic disease, participants with active known or suspected autoimmune disease, and prior treatment with any drug that targets T cell co-stimulations pathways are not eligible to participate.²

A full evaluation of the CheckMate 816 results is ongoing, and data will be shared at an upcoming medical conference.

“CheckMate -816 is the first phase 3 trial with an immunotherapy-based combination to demonstrate a statistically significant and clinically meaningful benefit as a neoadjuvant treatment for patients with non-metastatic non-small cell lung cancer. The combination of Opdivo plus chemotherapy first showed a statistically significant improvement in pathologic complete response rate without impacting surgical outcomes and has now extended the time patients live free of disease progression, recurrence or death,” said Abderrahim Oukessou, MD, vice president, thoracic cancers development lead, Bristol Myers Squibb, in a press release. “The event-free survival data from CheckMate -816 strengthen the evidence for the potential of Opdivo-based therapies to improve long-term clinical outcomes when used in the earlier stages of non-metastatic cancers.”

_REFERENCES:

_{1.Neoadjuvant Opdivo (nivolumab) plus chemotherapy significantly improves event-free survival in patients with resectable non-small cell lung cancer in phase 3 CheckMate -816 trial. News release. Bristol Myers Squibb. November 8, 2021. Accessed November 8, 2021. https://bit.ly/3kje4ob}

_{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. Accessed November 8, 2021. https://bit.ly/2YrMEF7}

_{3.Neoadjuvant Opdivo (nivolumab) plus chemotherapy significantly improves pathologic complete response in patients with resectable non-small cell lung cancer in phase 3 CheckMate -816 Trial. News release. Bristol Myers Squibb. April 4, 2021. Accessed November 8, 2021. https://bit.ly/3ki3Zbd}

_{4.Surgical outcomes from the phase 3 CheckMate 816 trial: Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo alone as neoadjuvant treatment for patients with resectable non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39(15):8503. doi: 10.1200/JCO.2021.39.15_suppl.8503}