EMA Recommends Approval of Neoadjuvant Nivolumab/Chemotherapy in Resectable NSCLC

May 26, 2023

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of nivolumab as neoadjuvant therapy in combination with platinum-based chemotherapy for patients with resectable non–small cell lung cancer at high risk of recurrence and tumor cell PD-L1 expression of at least 1%.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of nivolumab (Opdivo) as neoadjuvant therapy in combination with platinum-based chemotherapy for patients with resectable non–small cell lung cancer (NSCLC) at high risk of recurrence and tumor cell PD-L1 expression of at least 1%.¹

The positive opinion is based on data from the pivotal, phase 3 CheckMate-816 trial (NCT02998528), in which the addition of nivolumab (n = 179) led to a median event-free survival of 31.6 months (95% CI, 30.2–not reached) vs 20.8 months (95% CI, 14.0-26.7) with chemotherapy alone (n = 179; HR, 0.63; 97.38% CI, 0.43-0.91; P =.005). In addition, the combination induced pathologic complete response (pCR) rate of 24% (95% CI, 18.0%-31.0%) vs 2.2% (95% CI, 0.6%-5.6%) with chemotherapy alone, meeting the co-primary end points of the study (odds ratio, 13.94; 99% CI, 3.49-55.75; P < .001).²

“The devastating reality is that despite progress in lung cancer treatment, many patients still ultimately end up relapsing and potentially dying of their disease,” Abderrahim Oukessou, MD, vice president, thoracic cancers development lead, Bristol Myers Squibb, said in a news release. “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. 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.”

In March 2022, the FDA approved nivolumab plus platinum-based chemotherapy in the neoadjuvant setting for patients with resectable NSCLC based on findings from CheckMate-816.³

The randomized, open-label, multicenter phase 3 study enrolled patients with resectable stage IB to IIIA NSCLC per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control staging criteria. In addition to the co-primary end points of EFS and pCR, secondary end points included overall survival, major pathologic response, and time to death or distant metastases.

In March 2023, updated 3-year findings from the study were presented at the European Lung Cancer Congress.⁴ At a median follow up of 41.4 months, the 3-year EFS rate was 57% with the combination vs 43% with chemotherapy alone (HR, 0.68; 95% CI, 0.49-0.93). Additionally, time to distant metastasis or death (TTDM), defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis, continued to support the addition of nivolumab to chemotherapy compared with chemotherapy alone (HR, 0.55; 95% CI, 0.39-0.78), with 3-year TTDM rates of 71% vs 50%, respectively.

Although OS data have yet to mature, there was a continued trend in favor of the combination compared with chemotherapy alone (HR, 0.62; 99.34% CI, 0.36-1.05). The 3-year OS rate with the combination and chemotherapy alone was 78% and 64%, respectively.

Exploratory analyses were also conducted to evaluate EFS by surgical approach, EFS by extent or completeness of resection, and EFS and pCR by a four-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score. Results showed that the combination continued to elicit improved EFS at 3 years compared with chemotherapy in patients who had surgery, regardless of surgical approach or extent of resection, and in patients with R0 resection.

Additionally, baseline four-gene inflammatory signature scores were numerically higher in the combination arm in patients with pCR vs patients without pCR. Moreover, higher baseline inflammatory scores were associated with improved EFS with the combination compared with those who had lower scores.

Continued follow-up confirmed that the safety profile of the combination was consistent with the primary analysis, with no new safety signals. Grade 3/4 treatment-related and surgery-related adverse effects occurred in 36% and 11% of patients in the combination arm, respectively, vs 38% and 15% in the chemotherapy arm, respectively.

References

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 26, 2023. https://news.bms.com/news/details/2023
Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973-1985. doi:10.1056/NEJMoa2202170
US 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 26, 2023. https://news.bms.com/news/details/2022/
Neoadjuvant Opdivo (nivolumab) with chemotherapy demonstrates long-term durable clinical benefits for patients with resectable non-small cell lung cancer at three years in the CheckMate-816 trial. News release. Bristol Myers Squibb. March 30, 2023. Accessed May 26, 2023. https://news.bms.com/news/corporate-financial/2023