Perioperative Nivolumab Boosts NSCLC Survival: CheckMate 77T Trial

Perioperative administration of nivolumab plus chemotherapy bests chemotherapy alone in producing longer event-free survival (EFS) among adult patients who have resectable stage II/IIIb non–small cell lung cancer (NSCLC), according to new findings from an interim analysis of the CheckMate 77T trial published in The New England Journal of Medicine.¹ Perioperative administration means that nivolumab is administered as neoadjuvant and adjuvant treatment.

The phase 3 CheckMate 77T trial is currently investigating—the projected completion date is September 30, 2024—neoadjuvant chemotherapy with either nivolumab immunotherapy or placebo followed with surgical resection and adjuvant nivolumab or placebo treatment. Neoadjuvant treatment was administered every 3 weeks for 4 cycles, at a dose of 360 mg, and adjuvant for every 4 weeks for 1 year, at a dose of 480 mg.² EFS is the primary outcome, and pathological complete response (PCR) and major pathological response (mPR), secondary outcomes. Patients were randomized 1:1, and then stratified by disease stage (II or III), tumor histology (squamous cell or nonsquamous cell), and PD-L1 expression (< 1%, ≥1%, not evaluable or indeterminate).

Among those receiving nivolumab and chemotherapy (m = 229), 18-month EFS was 70.2% vs 50% of those receiving placebo and chemotherapy (n = 232), for a 42% reduced risk of disease progression or recurrence, abandoned surgery, or death (HR, 0.58; 95% CI, 0.42-0.81; P < .001). There also was close to a 6-fold higher chance of PCR with nivolumab compared with chemotherapy (25.5% vs 4.7%; OR, 6.64; 95% CI, 3.40-12.97), and a 3-fold higher chance of mPR (35.4% vs 12.1%; OR, 4.01; 95% CI, 2.48-6.49).

The median follow-up was 25.4 months (range, 15.7-44.2), median patient age was 66 years, and most patients in each group were male patients (72.9%, nivolumab; 69%, chemotherapy alone) and White (67.7% and 75.4%, respectively) or Asian (28.8% and 21.6%).

The study authors highlight that a perioperative treatment approach for cancer that includes immunotherapy can help to reduce relapse risk beyond the benefits of adjuvant alone and best supportive care.

Most patients in each group received neoadjuvant treatment: 99.6% of the nivolumab cohort and 99.1% of the chemotherapy-alone group; 84.7% and 88.5%, respectively, completed the 4 cycles. Definitive surgery, or surgery with curative intent, was then performed in 77.7% and 76.7%, with lobectomy being the most common in both (79.8% and 71.9%, respectively).

The following results were also seen:

• Those with tumor PD-L1 expression of 1% or more had a 48% (HR, 0.52; 95% CI, 0.35-0.78) reduced chance of EFS vs 27% (HR, 0.73; 95% CI, 0.47-1.15) in those with tumor PD-L1 expression less than 1%
• PCR occurred in 25.3% of the nivolumab group and 4.7% of the chemotherapy-alone group
• mPR occurred in 35.4% and 12.1%, respectively
• Treatment-related adverse events (TRAEs)of any grade occurred in 89% and 87%
• Grade 3/4 TRAEs occurred in 32.5% and 25.2%, and the most common was decreased neutrophil count
• Most common surgery-related AEs were incision-site pain (6.2% and 6.7%), procedural pain (5.6% and 1.7%), and dyspnea (5.1% and 6.2%)
• Four patients overall died, 3 who receive nivolumab and 1 who received chemptherapy alone

“This study builds on the standard-of-care neoadjuvant chemoimmunotherapy treatment and supports perioperative nivolumab as an effective approach that reduces the risk of lung cancer relapse,” principal investigator Tina Cascone, MD, PhD, associate professor of thoracic/head & neck medical oncology, MD Anderson, said in a statement. “These findings add to evidence that the perioperative immunotherapy path gives patients with operable lung cancer an opportunity to live longer without their cancer returning.”3

The biggest limitation on these findings is that few patients of a Black race/ethnicity were included, just 1.7% of each patient cohort.

Neoadjuvant nivolumab is a standard treatment for resectable NSCLS, backed by data from several phase 2 trials and the phase 3 CheckMate 816 trial.⁴ Together with an interim analysis of CheckMate 816, these data led to the approval of neoadjuvant nivolumab plus chemotherapy in the US, the European Union, Canada, China, and Japan.^5-9

References

1. Cascone T, Awad MM, Spicer JD, et al. Perioperative nivolumab in resectable lung cancer. N Engl J Med. 2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926 https://www.nejm.org/media/doi/pdf/10.1056/NEJMoa2311926

2. A study of neoadjuvant chemotherapy plus nivolumab versus neoadjuvant chemotherapy plus placebo, followed by surgical removal and adjuvant treatment with nivolumab or placebo for participants with surgically removable early stage non-small cell lung cancer. ClinicalTrials.gov. Updated April 8, 2024. Accessed May 16, 2024. https://clinicaltrials.gov/study/NCT04025879

3. Pre- and post-surgical immunotherapy improves outcomes for patients with operable lung cancer. News release. MD Anderson. May 15, 2024. Accessed May 16, 2024. https://www.mdanderson.org/newsroom/esmo-pre-post-surgical-immunotherapy-improves-outcomes-patients-operable-lung-cancer.h00-159622590.html

4. Forde PN, 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/NEJMoa220217

5. Opdivo (nivolumab). Prescribing information. Bristol Myers Squibb; 2024. Accessed May 16, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125554s128lbl.pdf

6. Opdivo (nivolumab). Summary of product characteristics. Bristol Myers Squibb Pharma EEIG; 2023. Accessed May 16, 2024. https://www.ema.europa.eu/en/documents/product-information/opdivo-epar-product-information_en.pdf

7. Opdivo: nivolumab for injection. Product monograph. Bristol Myers Squibb Canada; 2023. Accessed May 16, 2024. https://pdf.hres.ca/dpd_pm/00073986.PDF

8. Instructions for Opdivo (nivolumab) injection. In Chinese. Bristol Myers Squibb; 2023. https://www.bms.com/assets/bms/china/restricted/pi/OPDIVO_20230727.pdf

9. Opdivo (nivolumab) package insert. Pharmaceuticals and Medical Devices Agency; 2023. (In Japanese) https://www.pmda.go.jp/PmdaSearch/iyakuDetail/180188_4291427A1024_1_65