Patients with stage 3 N2 and stage 3 non-N2 non-small cell lung cancer (NSCLC) treated with presurgical Opdivo (nivolumab) plus chemotherapy, followed by surgery and then postsurgical Opdivo, experienced a significant improvement in event-free survival (EFS; the time a patient lives without complications from their disease), according to exploratory results from the phase 3 CheckMate 77T trial presented at the 2024 ASCO Annual Meeting.
Data showed that in patients with stage 3 N2 disease (cancer that has spread to nearby lymph nodes), the median EFS was 30.2 months with Opdivo (91 patients) compared with 10 months with placebo (inactive treatment; 90 patients), leading to a 54% improvement in EFS with the Opdivo regimen. The 12-month EFS rates were 70% and 45%, respectively.
For those with stage 3 non-N2 disease, the median EFS from randomization was not reached, meaning more than half of the patients in that population hadn’t experienced complications from their disease, with Opdivo (55 patients) versus 17 months with placebo (57 patients). The 12-month EFS rates were 74% and 62%, respectively.
Landmark EFS was also analyzed from the time point of definitive surgery. The median EFS in patients with stage 3 N2 disease was not reached with Opdivo (70 patients) compared with 8.9 months with placebo (66 patients). For patients with stage 3 non-N2 disease, the median EFS was not reached with Opdivo (45 patients) compared with 25 months with placebo (45 patients).
Additional results showed that the pathologic complete response (pCR; disappearance of cancer) rate in patients with stage 3 N2 disease was 22% compared with 5.6% in the placebo group. In those with stage 3 non-N2 disease, the pCR rates were 25.5% and 5.3%, respectively.
Findings also showed that patients with stage 3 N2 disease had similar rates of surgical feasibility as patients with non-N2 disease following neoadjuvant (presurgical) Opdivo and chemotherapy. In the stage 3 N2 subgroup, 77% of Opdivo-treated patients underwent surgery versus 73% of those on placebo. pCR rates in this group were 28.6% versus 7.6% with Opdivo versus placebo, respectively. Resection (surgical removal of cancer) results were similar in the stage 3 non-N2 subgroup; 82% of those on Opdivo and 79% of those on placebo underwent resection, with pCR rates of 31.1% and 6.7%, respectively.
“These findings, along with previously reported results from the CheckMate 77T study, further support perioperative [Opdivo] as a potential new treatment for patients with resectable NSCLC, including those with poor prognosis such as stage 3 N2,” said senior study author Dr. Tina Cascone, of The University of Texas MD Anderson Cancer Center in Houston, in an oral presentation of the data.
In February 2024, the Food and Drug Administration accepted a supplemental biologics license application seeking the approval of neoadjuvant Opdivo plus chemotherapy followed by surgery and adjuvant (postsurgical) Opdivo as a perioperative treatment of patients with resectable stage 2A to 3B NSCLC, based on earlier CheckMate 77T results.
Previous findings from CheckMate 77T showed that perioperative (around the time of surgery) Opdivo led to a significant improvement in EFS versus placebo in patients with stage 2 to 3B resectable NSCLC. At 12 and 18 months, the EFS rates with Opdivo were 73% and 70% versus 59% and 50% with placebo. Additionally, the pCR rates were 25.3% with Opdivo and 4.7% with placebo.
At the 2024 ASCO Annual Meeting, Cascone reported on the clinical outcomes from CheckMate 77T for patients with baseline stage 3 N2 and non-N2 NSCLC. Stage 3A to B resectable NSCLC is generally linked with poor survival outcomes, with five-year overall survival (OS; the time a patient lives, regardless of disease status) rates ranging from 24% to 41%.
A total 461 patients were randomized to receive Opdivo or placebo every three weeks plus chemotherapy every three weeks. Upon radiologic restaging, both groups went on to surgery within six weeks of post-neoadjuvant treatment. In the experimental group, Opdivo was then given at 480 milligrams every four weeks for 13 cycles and those in the placebo group received placebo for the same number of cycles and duration.
The median follow-up was 25.4 months, with a database lock date of Sept. 6, 2023.
Regarding safety, most patients in both groups and subgroups experienced side effects. In the stage 3 N2 subgroup, all-grade and grade 3 (severe) to 4 (life-threatening) treatment-related side effects occurred in 90% and 34%, respectively, of Opdivo-treated patients versus 87% and 26% of placebo-treated patients. All-grade and grade 3 to 4 side effects leading to discontinuation occurred in 31% and 18% of patients versus 9% and 4%, respectively. All-grade and grade 3 to 4 treatment-related side effects that led to discontinuation were reported in 25% and 15% of patients on Opdivo and 7% and 4% of those on placebo. All-grade and grade 3 to 4 serious side effects occurred in 44% and 28% on Opdivo and 27% and 16% on placebo. Finally, all-grade and grade 3 to 4 treatment-related serious side effects were reported in 26% and 15%, respectively, of those on Opdivo compared with 11% and 7% of those on placebo.
In the stage 3 non-N2 subgroup, all-grade and grade 3 to 4 treatment-related side effects occurred in 87% and 29%, respectively, of Opdivo-treated patients versus 84% and 21% of placebo-treated patients. All-grade and grade 3 to 4 side effects leading to discontinuation occurred in 20% and 7% versus 10% and 7%, respectively. All-grade and grade 3 to 4 treatment-related side effects that led to discontinuation were reported in 14% and 6% of patients on Opdivo and 7% and 5% of those on placebo. All-grade and grade 3 to 4 serious side effects occurred in 38% and 22% of those on Opdivo and 35% and 21% of those on placebo. Finally, all-grade and grade 3 to 4 treatment-related serious side effects were reported in 9% and 6%, respectively, of those on Opdivo compared with 10% and 7% of those on placebo.
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