Perioperative nivolumab improves NSCLC survival: CheckMate 77T study

Perioperative administration of nivolumab and chemotherapy is superior to chemotherapy alone in prolonging event-free survival (EFS) in adult patients with resectable stage II/IIIb disease. Non-small cell lung cancer (NSCLC)According to new findings from an interim analysis of the CheckMate 77T exam, published in New England Medical Journal.¹ Perioperative administration means that nivolumab is administered as neoadjuvant and adjuvant therapy.

Main interim analysis data

• Patients were randomized 1:1 to nivolumab plus chemotherapy (n = 229) or chemotherapy alone (n = 232).
• Among patients who received neoadjuvant therapy, 84.7% of patients who received nivolumab and 88.5% of patients who received chemotherapy alone completed all four treatment cycles.
• Lobectomy was the most common form of curative surgery (79.8% and 71.9%, respectively)
• Overall, four patients died, three in the nivolumab group and one in the chemotherapy alone group.

The Phase 3 CheckMate 77T trial is currently under investigation with an expected completion date of September 30, 2024. Neoadjuvant chemotherapy with nivolumab immunotherapy or placebo followed by surgical resection and adjuvant nivolumab or placebo treatment is performed. Neoadjuvant treatment was administered at a dose of 360 mg every 3 weeks for 4 cycles, and adjuvant was administered at a dose of 480 mg every 4 weeks for 1 year.² EFS is the primary outcome, and pathological complete response (PCR) and major pathological response (mPR) are secondary outcomes. Patients were randomized 1:1 and then evaluated for stage (II or III), tumor histology (squamous or non-squamous), PD-L1 expression (<1%, ≥1%, stratified by (incapacitated or indeterminate).

The 18-month EFS for patients receiving nivolumab and chemotherapy (m = 229) was 70.2%, compared with 50% for patients receiving placebo and chemotherapy (n = 232) with no disease progression or recurrence; The risk of abandonment, or abandonment of surgery, was reduced by 42%. Death (HR, 0.58; 95% CI, 0.42-0.81; P < .001). Nivolumab was also nearly 6 times more likely to have PCR compared to chemotherapy (25.5% vs 4.7%; OR, 6.64; 95% CI, 3.40-12.97) and 3 times more likely to have mPR (35.4%). vs. 12.1%, OR, 4.01, 95% CI, 2.48-6.49).

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 (72.9% in the nivolumab group, 69% on chemotherapy alone) and Caucasian patients (in the nivolumab group). 67.7%, chemotherapy alone 69%). 75.4%) or Asian (28.8% and 21.6%, respectively).

The study authors highlight that perioperative treatment approaches for cancer, including immunotherapy, may help reduce the risk of recurrence beyond the benefits of adjuvant alone or best supportive care.

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

The following results were also observed:

• Patients with tumor PD-L1 expression ≥1% had a decreased odds of EFS of 48% (HR, 0.52; 95% CI, 0.35-0.78) compared with 27% (HR, 0.73; 95% CI, 0.47-1.15) decreased.Tumor PD-L1 expression is 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%, with decreased neutrophil count being the most common
• The 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%).
• Overall 4 patients died, 3 received nivolumab and 1 received chemotherapy only

“This study builds on the standard of care neoadjuvant chemoimmunotherapy and supports perioperative nivolumab as an effective approach to reduce the risk of lung cancer recurrence,” said the principal investigator. said Tina Cascone, MD, associate professor of thoracic/head and neck medicine. Oncology, MD Anderson; stated in a statement. “These findings add to the evidence that perioperative immunotherapy gives patients with operable lung cancer the chance to live longer without cancer recurrence.”3

The biggest limitation of these findings is that they rarely included patients of black race/ethnicity, representing only 1.7% of each patient cohort.

Neoadjuvant nivolumab is the standard treatment for resectable NSCLS, supported by data from several phase 2 and phase 3 CheckMate 816 trials.^Four Together with the interim analysis of CheckMate 816, these data led to the approval of neoadjuvant nivolumab and chemotherapy in the United States, European Union, Canada, China, and Japan.^5-9

References

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

2. Neoadjuvant chemotherapy plus nivolumab versus neoadjuvant chemotherapy plus placebo, followed by surgical resection and adjuvant treatment with nivolumab or placebo in participants with surgically resectable early-stage non-small cell lung cancer. the study. ClinicalTrials.gov. Updated on April 8, 2024. Accessed May 16, 2024. https://clinicaltrials.gov/study/NCT04025879

3. Pre- and Post-Surgery 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 and chemotherapy for resectable lung cancer. N English J Medicine. 2022;386(21):1973-1985. doi:10.1056/NEJMoa220217

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

6. Opdivo (nivolumab). We have summarized the product features. 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: Injectable nivolumab. Product monograph. Bristol-Myers Squibb Canada; 2023. Accessed May 16, 2024. https://pdf.hres.ca/dpd_pm/00073986.PDF

8. Opdivo (nivolumab) injection instructions. 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. https://www.pmda.go.jp/PmdaSearch/iakuDetail/180188_4291427A1024_1_65