Patients with resectable (surgically unremovable) non-small cell lung cancer (NSCLC) undergoing treatment with perioperative Opdivo (nivolumab) demonstrated extended event-free survival (EFS; living without complications or disease worsening) versus placebo, according to findings from a phase 3 trial.
Updated data from the phase 3 CheckMate 77T trial presented during the 2024 ESMO Congressdemonstrated that, at a median follow-up of 33.3 months, 229 patients who received perioperative Opdivo achieved a median EFS of 40.1 months compared with 17 months among 232 patients who received placebo. The 12-month EFS rates were 73% versus 59%, and the 24-month rates were 65% versus 44%, respectively.
In the trial, patients had resectable stage 2A to 3B NSCLC and had not previously received systemic anti-cancer treatment. Eligible patients also had an ECOG performance of 0 or 1, meaning they could perform daily tasks independently, and also did not have EGFR mutations or known ALK translocations.
Patients were randomly assigned to receive either Opdivo plus chemotherapy (229 patients) or placebo plus chemotherapy (232 patients). Both groups of patients received surgery and then adjuvant (postsurgical) Opdivo, according to the study.
The primary goal of the trial was EFS and secondary goals included pCR and major pathologic response rates, as well as overall survival (OS; time patients live, regardless of their disease status) and safety.
EFS Findings from the Phase 3 Study
Among 58 patients who received Opdivo and experienced a pathologic complete response (pCR; disappearance of the tumor) also experienced a significant EFS benefit versus 11 patients who received placebo. Similarly, 98 patients without a pCR in the Opdivo group also experienced an EFS benefit compared with 148 patients who received placebo and did not achieve a pCR.
During the postoperative period, evaluable patients in the Opdivo group (48 patients) and the placebo group (44 patients) experienced circulating tumor DNA (ctDNA; remaining tumor cells present in the bloodstream) recurrence at rates of 8% versus 20%, respectively. Evaluable patients with a pCR in the Opdivo (26 patients) and placebo groups (5 patients) experienced ctDNA recurrence at rates of 4% versus 20%, respectively. Evaluable patients without a pCR in the Opdivo (22 patients) and placebo groups (39 patients) experienced ctDNA recurrence at rates of 14% versus 21%, respectively.
“[The EFS data] show an improvement that is both statistically and clinically significant with the addition of perioperative [Opdivo], with an increase in median EFS from 17 months to 40.1 months with the addition of perioperative [Opdivo],” Dr. Jonathan D. Spicer, said during the presentation. “The addition of perioperative [Opdivo] provided some benefit, both in the pCR and the non-pCR patients with HRs that are commensurate to the degree of pathological response. … These data support the use of perioperative [Opdivo] as an efficacious regimen for patients with resectable NSCLC.”
Spicer is the Dr. Ray Chiu Distinguished Scientist in Surgical Research, the Advanced Thoracic and Upper GI Surgical Oncology Fellowship program director, the Rossy Cancer Network Lung Cancer Disease Site Lead, and an attending surgeon in the Division of Thoracic and Upper Gastrointestinal Surgery at McGill University Health Centre in Montreal, Canada.
Safety Outcomes for Patients With Unresectable NSCLC
In terms of safety, a total of 58 patients in the Opdivo and 11 patients in the placebo groups who achieved a pCR experienced an any-grade side effect. Patients in both groups also experienced grade 3 (severe) to 4 (life-threatening) side effects (48% versus 46%), any-grade treatment-related side effects (97% versus 82%), any-grade serious side effects (43% versus 36%) and grade 3 to 4 serious side effects (28% versus 36%).
In the Opdivo group, grade 3 to 4 treatment-related side effects (31%), any-grade side effects leading to treatment discontinuation (34%), grade 3 to 4 side effects leading to treatment discontinuation (17%), any-grade treatment-related side effects leading to discontinuation (29%), any-grade treatment-related serious side effects (24%) and grade 3 to 4 treatment-related serious side effects (14%) were also reported; no patients in the placebo group experienced these events.
Patients without a pCR in the Opdivo (170 patients) and placebo (219 patients) groups experienced any-grade side effects (96% versus 98%), grade 3 to 4 side effects (46% versus 42%), any-grade treatment-related side effects (86% versus 87%), grade 3 to 4 treatment-related side effects (32% versus 26%), any-grade side effects leading to treatment discontinuation (22% versus 11%), grade 3 to 4 side effects leading to treatment discontinuation (13% versus 6%), any-grade treatment-related side effects leading to treatment discontinuation (16% versus 8%), and grade 3 to 4 treatment-related side effects leading to treatment discontinuation (10% versus 5%). Additionally, any-grade serious side effects (42% versus 31%), grade 3 to 4 serious side effects (29% versus 19%), any-grade treatment-related serious side effects (17% versus 10%) and grade 3 to 4 treatment-related serious side effects (14% versus 6%) also occurred.
Overall, two treatment-related deaths were reported in the Opdivo group, both because of pneumonitis (inflammation in the lung tissue).
“Low-grade [side effects] and [treatment-related side effects] are a bit more common in the pCR group versus the non-pCR group,” Spicer noted. “In total, these data are consistent with prior reports showing a significant improvement in EFS in the [Opdivo] cohort versus placebo. ... Exploratory ctDNA analyses indicate that ctDNA clearance is indicative of a higher likelihood of pCR and, perhaps more importantly, the lack of clearance is associated with residual disease.”
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