EU’s CHMP Recommends Nivolumab/Chemo for Approval in Resectable NSCLC

The safety profile of nivolumab in the Checkmate 816 trial was consistent with prior reports of the agent in the management of NSCLC.

The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has recommended approving nivolumab (Opdivo) plus platinum-containing chemotherapy as a neoadjuvant treatment for patients with resectable, PD-L1–positive non–small cell lung cancer (NSCLC) at a high risk of recurrence, according to a press release from Bristol Myers Squibb.¹

The CHMP based its recommendation on findings from the phase 3 Checkmate 816 trial (NCT02998528). According to data from the trial that were published in The New England Journal of Medicine, the median event-free survival (EFS) was 31.6 months (95% CI, 30.2-not reached [NR]) with nivolumab plus chemotherapy vs 20.8 months (95% CI, 14.0-26.7) with chemotherapy alone (Hazard ratio, 0.63; 97.38% CI, 0.43-0.91; P = .005)². The estimated percentage of patients without disease progression or disease recurrence was 76.1% vs 63.4% at 1 year and 63.8% vs 45.3% at 2 years in each respective treatment group.

Investigators also identified benefit with nivolumab plus chemotherapy with respect to pathological complete response (pCR) across PD-L1 subgroups, as well as greater EFS benefit in those with a PD-L1 tumor expression of 1% or more compared with those with a level of less than 1%.

The safety profile of nivolumab in the Checkmate 816 trial was consistent with prior reports of the agent in the management of NSCLC.

“Based on the results of the CheckMate 816 trial, [nivolumab] with chemotherapy is the first immunotherapy-based regimen to reduce the risk of disease recurrence, progression and death in resectable NSCLC when given before surgery,” Abderrahim Oukessou, MD, vice president and Thoracic Cancers Development lead at Bristol Myers Squibb, said in the press release.

“The CHMP’s recommendation moves us another step closer to addressing the pressing need to offer certain patients in the European Union a chance to change the course of their disease with an effective and tolerable pre-surgical option that may help reduce the risk of relapse.”

Investigators of the open-label, multi-center phase 3 CheckMate 816 trial assessed nivolumab in combination with chemotherapy vs chemotherapy alone in the neoadjuvant treatment of patients with resectable stage IB to IIIA NSCLC. In the primary analysis, 358 patients were randomly assigned to receive 360 mg of nivolumab plus platinum-doublet chemotherapy every 3 weeks for 3 cycles or chemotherapy on its own followed by surgery.

The primary end points of the trial were EFS and pCR. Secondary end points included major pathologic response rate, overall survival, and time to death or distant metastases.

Patients 18 years and older with operable NSCLC confirmed in tissue and lung function capacity capable of tolerating the proposed lung surgery were eligible for enrollment on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 and available tissue of primary lung tumor.

Patients with locally advanced, inoperable, or metastatic disease or active, known, or suspected autoimmune disease were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had received prior treatment with any agent that targets T-cell co-stimulation pathways including checkpoint inhibitors.

The FDA previously approved neoadjuvant nivolumab plus chemotherapy for certain patients with resectable NSCLC in March 2022.³ The agency based its approval on results from the CheckMate 816 study.

“The approval of nivolumab with platinum-doublet chemotherapy marks a turning point in how we treat resectable NSCLC, and it enables us to use immunotherapy and chemotherapy as neoadjuvant treatment for patients before surgery,” study investigator Mark Awad, MD, PhD, associate professor of Medicine at Harvard Medical School and clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said in a press release at the time of the FDA approval.

References

1. Bristol Myers Squibb receives positive CHMP opinion recommending approval for Opdivo (nivolumab) with chemotherapy as neoadjuvant treatment of resectable non-small cell lung cancer at high risk of recurrence in patients with tumor cell PD-L1 expre... News release. Bristol Myers Squibb. May 26, 2023. Accessed May 31, 2023. bit.ly/3N1Y7Sf
2. Forde PM, Spicer J, Lu S, Provencio-Pulla M, et al; CheckMate 816 Investigators. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973-1985. doi:10.1056/NEJMoa2202170.
3. U.S. Food and Drug Administration approves Opdivo (nivolumab) with chemotherapy as neoadjuvant treatment for certain adult patients with resectable non-small cell lung cancer. News release. Bristol Myers Squibb. March 4, 2022. Accessed May 31, 2023. https://bit.ly/3INrdQA