Spicer J, et al. Abstract 8503. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
Bristol Myers Squibb supported this study. Spicer reports consultant/advisory roles with AstraZeneca and Bristol Myers Squibb; research funding from AstraZeneca, Merck and Roche; and honoraria from AstraZeneca, Bristol Myers Squibb and Merck. Please see the abstract for all other researchers’ relevant financial disclosures.
The addition of nivolumab to neoadjuvant chemotherapy appeared safe and did not impact timing or feasibility of surgery among patients with resectable non-small cell lung cancer, according to results of the phase 3 CheckMate 816 trial.
The results, presented during the virtual ASCO Annual Meeting, also showed improvements in pathologic complete response regardless of disease stage with the addition of nivolumab (Opdivo, Bristol Myers Squibb) to chemotherapy.
“Single-arm, phase 2 trials incorporating neoadjuvant checkpoint blockade have shown encouraging efficacy outcomes in terms of pathologic complete response, EFS and OS without compromising the feasibility of surgery for patients with resectable NSCLC,” Jonathan Spicer, MD, assistant professor of surgery at McGill University and attending surgeon in the division of thoracic and upper gastrointestinal surgery at Montreal General Hospital in Canada, said during his presentation. “During the 2021 virtual American Association for Cancer Research Annual Meeting, Patrick M. Forde, MD, presented the first positive, independent primary endpoint from CheckMate 816 demonstrating significantly improved pathologic complete response after neoadjuvant nivolumab plus chemotherapy. Here, we present additional efficacy data segregated by disease stage, as well as key surgical outcomes from CheckMate 816.”
The randomized trial included 358 patients with clinical stage IB to stage IIIA resectable NSCLC, an ECOG performance status of 0 to 1 and no known EGFR/ALK alterations. Researchers randomly assigned patients to platinum-doublet chemotherapy every 3 weeks for three cycles with (n = 179) or without (n = 179) 360 mg nivolumab every 3 weeks, followed by surgical resection within 6 weeks after treatment.
The combination and chemotherapy groups had similar baseline characteristics, including median age (64 years vs. 65 years), sex (women, 28% vs. 29%), smoking status (current/former, 89% vs. 88%) and histology (squamous, 49% vs. 53%). Most patients in each group had stage IIIA disease (63% vs. 64%), and half had tumor PD-L1 expression of at least 1%.
Pathologic complete response, defined as the absence of viable tumor cells in lung and lymph nodes, and EFS served as co-primary endpoints. Secondary endpoints include major pathological response and OS. Exploratory endpoints included feasibility of surgery and surgery-related adverse events.
“We previously showed the pathologic complete response rates were 24% with nivolumab plus chemotherapy vs. 2.2% with chemotherapy alone in the intent-to-treat population,” Spicer said. “Results of the current study showed an improvement in pathologic complete response rates regardless of disease stage compared with chemotherapy alone.”
These included rates of 40% vs. zero among patients with stage IB disease, 23% vs. 3% among those with stage IIA disease, 24% vs. 9% among those with stage IIB disease and 23% vs. 1% among those with stage IIIA disease.
Most patients (83%) in the nivolumab group completed surgery, compared with 75% in the chemotherapy-alone group. Median surgery duration was 184 minutes vs. 217 minutes.
“This half-hour difference in procedure time may indicate surgical complexity was not increased by virtue of the addition of the nivolumab preoperative treatment regimen,” Spicer said.
Common reasons for surgery cancellation included disease progression (nivolumab group, n = 12; chemotherapy group, n = 17), adverse events (n = 2 vs. 2) or other reasons (n = 14 vs. 19), which included patient refusal, unresectable disease and poor lung function.
“However, cancellation of surgery due to neoadjuvant therapy toxicity was rare, with only 1% incidence in each arm,” Spicer said.
Moreover, a greater proportion of patients in the nivolumab group had minimally invasive surgery (30% vs. 22%), with a lower conversion rate from minimally invasive to open surgery than the chemotherapy-alone group (11% and 16%). About three-quarters (77%) of patients in the nivolumab group underwent lobectomy vs. 61% of patients in the chemotherapy-alone group, and 17% vs. 25% underwent pneumonectomy.
Researchers did not observe clinically meaningful differences in delays in time to surgery, with a median time to definitive surgery of 5.3 weeks with the nivolumab regimen and 5 weeks with chemotherapy alone, which is within excepted standards for a neoadjuvant therapeutic approach, Spicer said.
Overall, 83% of patients assigned the nivolumab regimen and 78% of patients assigned chemotherapy alone achieved R0 resection, with 10% vs. 74% median residual viable tumor cells in the primary tumor bed.
Fewer patients assigned nivolumab experienced adverse events that caused delays in surgery (n = 6 vs. 9) and a smaller proportion experienced any-grade surgery-associated adverse events (41% vs. 47%) and grade 3 to grade 4 surgery-associated adverse events (11% vs. 15%). Two patients assigned nivolumab experienced grade 5 surgery-associated adverse events compared with no patients assigned chemotherapy alone. However, no patients in the nivolumab group died due to treatment-related adverse events compared with three in the chemotherapy-alone group.
Data continue to mature for EFS, Spicer noted.
“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathologic complete response, support nivolumab in combination with chemotherapy as a potential neoadjuvant option for patients with resectable NSCLC,” Spicer said.