Madrid, Spain—A perioperative regimen of neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by surgery and adjuvant nivolumab demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS) versus neoadjuvant chemotherapy plus placebo followed by surgery and adjuvant placebo in patients with resectable non–small cell lung cancer (NSCLC). The benefit of nivolumab on EFS observed in the phase 3 CheckMate 77T clinical trial was present across most subgroups, according to Tina Cascone, MD, PhD, Associate Professor, Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, and lead investigator of the study, who presented the findings during the European Society for Medical Oncology Congress 2023.1
The rates of pathologic complete response (pCR) and major pathologic response rates were also improved with nivolumab.
“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care, neoadjuvant nivolumab plus chemotherapy, and supports perioperative nivolumab as a potential new treatment option for patients with resectable NSCLC,” said Dr Cascone. “Perioperative nivolumab demonstrated a statistically significant and clinically meaningful improvement in EFS versus chemotherapy,” she added.
The data presented were based on a September 6, 2023, database lock, with a median follow-up of 25.4 months. As of the database lock, overall survival (OS) has not yet been formally tested and continues to mature.
Study Details
The phase 3, double-blind, placebo-controlled, multicenter CheckMate 77T study randomized 461 patients with resectable stage IIA to IIIB NSCLC in a 1:1 ratio to neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab/chemotherapy arm) versus neoadjuvant chemotherapy plus placebo followed by surgery and adjuvant placebo (placebo/chemotherapy arm). At the time of enrollment, patients had no previous systemic anticancer therapy and no EGFR mutations or known ALK alterations. Following their last neoadjuvant treatment and radiologic restaging, patients had surgery within 6 weeks followed by nivolumab or placebo administered for 1 year.
The primary end point of the trial was EFS according to blinded independent central review. Secondary end points included OS, pCR, major pathologic response, and safety.
Baseline characteristics were well-balanced between the treatment arms. The median patient age was approximately 66 years. More than 50% of patients were from Europe and more than 20% from Asia. Approximately two-thirds of patients had stage III disease at presentation, and approximately 90% were either current smokers or had smoked in the past. More than 50% of patients in each arm had tumor PD-L1 expression ≥1%, and approximately 40% in each arm had tumor PD-L1 expression <1%. Most patients in both arms received carboplatin-based chemotherapy, and almost all patients in both arms received neoadjuvant treatment, with at least 35% completing 4 treatment cycles. Study drug toxicity was the most common reason for a neoadjuvant treatment discontinuation in both arms.
Some 78% of patients in the nivolumab arm and 77% of patients in the chemotherapy arm underwent definitive surgery. Nearly two-thirds of patients across both arms received adjuvant treatment, with a median number of 13 doses administered. Toxicity was the most common reason for not receiving adjuvant therapy in the nivolumab/chemotherapy arm, whereas disease progression was the most common reason in the placebo/chemotherapy arm. Lobectomy was the most common type of surgery, performed in 80% of patients in the nivolumab/chemotherapy arm and 72% of those in the placebo/chemotherapy arm.
Tina Cascone, MD, PhD
The University of Texas MD Anderson Cancer Center
CheckMate 77T is the first phase 3 perioperative study to build on the standard of care,…and supports perioperative nivolumab as a potential new treatment option for patients with resectable NSCLC.—Tina Cascone, MD, PhD
Results
Median EFS was not reached in the nivolumab/chemotherapy arm and was 18.4 months in the placebo/chemotherapy arm (hazard ratio [HR], 0.58; P=.00025). The 12-month EFS rates were 73% in the nivolumab/chemotherapy arm versus 59% in the placebo/chemotherapy arm; the 18-month EFS rates were 70% versus 50%, respectively, “suggesting greater benefit for patients over time,” Dr Cascone noted. EFS per investigative assessment also favored nivolumab versus chemotherapy (HR, 0.56).
“Nivolumab appeared to improve EFS versus chemotherapy regardless of the disease stage and in particular in patients with stage III disease,” said Dr Cascone. “Patients with nodal disease, including those with both single and multistation N2 status, had an improved EFS with nivolumab compared with chemotherapy. And the EFS favored nivolumab versus chemotherapy regardless of tumor histology, with a particularly clear benefit in patients with squamous disease.”
In patients with tumor PD-L1 expression <1%, the median EFS was 29 months in the nivolumab/chemotherapy arm and 19.8 months in the placebo/chemotherapy arm (HR, 0.73; 95% confidence interval [CI], 0.46-1.15). The magnitude of EFS benefit with nivolumab versus chemotherapy was numerically greater in those patients with tumor PD-L1 expression ≥1%, with a median EFS not reached in the nivolumab/chemotherapy arm versus 15.8 months in the placebo/chemotherapy arm (HR, 0.52; 95% CI, 0.35-0.78).
“Very importantly, a pCR was observed in 25.3% of patients in the nivolumab arm versus 4.7% of patients in the chemotherapy arm in the intention to treat population, representing more than a fourfold increase,” Dr Cascone said. A major pathologic response was observed in 35.4% of patients in the nivolumab arm versus 12.1% of those in the chemotherapy arm, representing nearly a threefold increase.
Neoadjuvant nivolumab plus chemotherapy continued to provide benefit over chemotherapy alone in patients who were not able to receive adjuvant therapy.
The perioperative nivolumab-based regimen showed no new safety signals. A similar percentage of patients in the nivolumab/chemotherapy and placebo/chemotherapy arms experienced grade 3/4 treatment-related adverse events (AEs). Any-grade treatment-related AEs were observed in 50% of patients treated with adjuvant nivolumab/chemotherapy and 30% of those treated with adjuvant placebo/chemotherapy. Any-grade surgery-related AEs were reported in 41% and 39% of patients, respectively.
Reference
- Cascone T, Awad MM, Spicer JD, et al. CheckMate 77T: phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant nivolumab or placebo for previously untreated, resectable stage II–IIIb NSCLC. Ann Oncol. 2023;34(suppl 2):S1295. Abstract book of the ESMO Congress 2023. doi:10.1016/j.annonc.2023.10.050