Nivolumab regimen improves outcomes in resectable non-small cell lung cancer
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Key takeaways:
- Use of nivolumab in the neoadjuvant and adjuvant settings significantly extended EFS.
- A higher percentage of nivolumab-treated patients achieved complete response and major pathologic response.
MADRID — The addition of nivolumab to neoadjuvant chemotherapy, followed by adjuvant nivolumab, improved outcomes for patients with untreated resectable non-small cell lung cancer, randomized phase 3 study results showed.
The combination conferred a statistically significant and clinically meaningful improvement in EFS, according to Tina Cascone, MD, PhD, associate professor in the department of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center.
The findings support perioperative nivolumab as a potential new treatment option for patients with resectable NSCLC, said Cascone, who presented the results at ESMO Congress.
Nivolumab and chemotherapy is the standard neoadjuvant treatment for eligible patients with resectable NSCLC. However, no phase 3 studies had evaluated the efficacy of perioperative nivolumab-chemotherapy treatment.
The double-blind CheckMate 77T trial included 461 adults with resectable stage II to stage IIIB NSCLC. All patients had EGFR/ALK wild-type disease and ECOG performance status of 0 or 1.
Researchers randomly assigned 229 patients to neoadjuvant treatment with 360 mg nivolumab every 3 weeks plus platinum doublet chemotherapy for four cycles, followed by surgery, followed by adjuvant therapy with 480 mg nivolumab every 4 weeks for up to 1 year. They assigned the other 232 patients to placebo plus neoadjuvant chemotherapy, followed by surgery, followed by placebo.
The groups appeared balanced with regard to baseline characteristics.
EFS served as the primary endpoint. Secondary endpoints included pathologic complete response and major pathologic response — both assessed by blinded independent review — as well as OS and safety.
A prespecified interim analysis performed after minimum follow-up of 15.7 months showed the study met its primary endpoint, demonstrating improved EFS in the nivolumab group (median, not reached vs. 18.4 months; HR = 0.58; 97.36% CI, 0.42-0.81).
The EFS benefit persisted regardless of disease stage, nodal status and tumor histology. Nivolumab improved EFS among patients with PD-L1 expression less than 1%, with a more profound benefit among those with PD-L1 expression of 1% or more, Cascone said.
Researchers also reported higher rates of pathologic complete response (25.3% vs. 4.7%; OR = 6.64; 95% CI, 3.4-12.97) and major pathologic response (35.4% vs. 12.1%; OR = 4.01; 95% CI, 2.48-6.49) in the nivolumab group.
A comparable percentage of patients in the nivolumab and placebo groups underwent definitive surgery (78% vs. 77%) and had R0 resection (89% vs. 90%).
Researchers observed no new safety signals with the nivolumab regimen.
A similar percentage of patients in the nivolumab and placebo groups experienced grade 3/grade 4 treatment-related adverse events (32% vs. 25%) and surgery-related adverse events (12% each).
Perspective
Back to TopMarina C. Garassino, MD
The HR of 0.58 is impressive and the result is highly statistically significant.However, there are still some open questions.
Are all the perioperative combinations similar in terms of efficacy? The answer, I think, is yes.
Should we give perioperative therapy to patients with stage II disease? These patients can be potentially be resectable from the beginning, and we know across all trials that about 20% of patients are not resectable after chemotherapy or after chemoimmunotherapy. An analysis of results of prior trials that included information about disease stage suggest we should treat patients with stage II disease, with a pooled HR of 0.68 (95% CI, 0.51-0.9).
Should we treat patients with PD-L1-negative status? Data from prior trials suggest the answer is yes, with a pooled HR of 0.72 (95% CI, 0.58-0.89).
The big question is whether perioperative therapy is superior to neoadjuvant only. I don’t think we really know.
We do know patients who achieved a complete pathologic response do very well. For those who do not achieve a complete pathologic response, we have to work with new biomarkers, circulating tumor DNA and new drugs, and we have to run proper trials to raise the bar for these patients which, unfortunately, is still very low.
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Cascone T, et al. Abstract LBA1. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
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