Neoadjuvant/Adjuvant Nivolumab/Chemo Approved by FDA in Resectable NSCLC

The FDA has approved nivolumab plus platinum-doublet chemotherapy for neoadjuvant treatment followed by single-agent nivolumab after surgery for patients with resectable non–small cell lung cancer with EGFR mutations or ALK rearrangement

The FDA has approved nivolumab (Opdivo) plus platinum-doublet chemotherapy for neoadjuvant treatment followed by single-agent nivolumab after surgery for patients with resectable non–small cell lung cancer with EGFR mutations or ALK rearrangement, according to a press release from the FDA.¹

The approval is based on results from the phase 3 CheckMate 77T trial (NCT04025879), which were presented at the 2023 European Society of Medical Oncology Congress.² The median event-free survival was not reached (95% CI, 28.9-not estimable [NE]) in the nivolumab arm vs 18.4 months (95% CI, 13.6-28.1) in the chemotherapy arm (HR, 0.58; 95% CI, 0.43-0.78; P = .00025). According to data from a prespecified interim analysis, nivolumab-based treatment yielded no detriment to overall survival (OS), although investigators did not formally evaluate this end point for statistical significance.

"Checkmate 77T is the first phase 3 perioperative study to build on the standard-of-care neoadjuvant nivolumab plus chemo and supports perioperative nivolumab as a potential new treatment option for patients with resectable non-small cell lung cancer,” Tina Cascone, MD, PhD, an associate professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, said in a presentation of these data at the 2023 ESMO Congress.²

Investigators presented other updated findings from CheckMate 77T at the 2024 ESMO Congress.³ These data showed a 12-month EFS rate of 73% (95% CI, 67%-79%) in the nivolumab arm vs 59% (95% CI, 52%-65%) in the placebo arm. At 24 months, the EFS rates in each respective arm were 65% (95% CI, 58%-71%) and 44% (95% CI, 38%-51%).

Patients who achieved a pathologic complete response (pCR) in the nivolumab arm (n = 58) also had a significant EFS benefit compared with those in the placebo arm (n = 11; HR, 0.59; 95% CI, 0.12-2.91). Even among those without a pCR, improvements in EFS occurred in the nivolumab arm (n = 98) vs the placebo arm (n = 148; HR, 0.75; 95% CI, 0.51-1.09).

Safety findings from CheckMate 77T were comparable with prior reports of nivolumab plus chemotherapy. Data showed that 5.3% in the nivolumab arm were unable to undergo surgery due to adverse effects (AEs) during neoadvjuant therapy vs 3.5% in the placebo arm. Among patients who received neoadjuvant treatment plus surgery, 4.5% and 3.9% of patients experienced delays in surgery due to AEs in the nivolumab and placebo arms, respectively.

The recommended dosing included 360 mg every 3 weeks as neoadjuvant treatment and 480 mg every 4 weeks as adjuvant treatment. Of note, nivolumab should be given prior to chemotherapy when administered on the same day.

In the CheckMate 77T trial, patients were randomly assigned 1:1 to receive nivolumab at 360 mg or matched placebo every 3 weeks followed by chemotherapy every 3 weeks for up to 4 cycles. Patients in both groups then underwent surgery before receiving adjuvant nivolumab at 480 mg every 4 weeks or placebo for a maximum of 13 cycles.

The trial's primary end point was EFS by blinded independent central review. Secondary end points included pCR and major pathologic response rates by blinded independent pathologic review, overall survival, and safety.

References

1. FDA approves neoadjuvant/adjuvant nivolumab for resectable non-small cell lung cancer. News release. FDA. October 3, 2024. Accessed October 3, 2024. https://shorturl.at/QGmg
2. Cascone T, Awad MM, Spicer J, et al. CheckMate 77T: Phase 3 study comparing neoadjuvant nivolumab plus chemotherapy with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant nivolumab or placebo for previously untreated, resectable stage II–IIIB NSCLC. Presented at: ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA1.
3. Pulla MP, Awad MM, Cascone T, et al. Perioperative nivolumab vs placebo in patients with resectable NSCLC: clinical update from the phase 3 CheckMate 77T study. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA50.