medwireNews: Neoadjuvant treatment with nivolumab plus chemotherapy achieves significantly better event-free survival (EFS) than chemotherapy alone, suggests the CheckMate 816 trial of patients with resectable non-small-cell lung cancer (NSCLC).
These findings back earlier results from the phase 3 trial showing that nivolumab addition significantly improved pathologic complete response (pCR) rates, but not at the cost of surgical delays or complications.
“On the basis of this trial, nivolumab in combination with chemotherapy has been approved in the United States as neoadjuvant treatment for adult patients with resectable NSCLC (tumors ≥4 cm or node positive),” write the researchers in The New England Journal of Medicine.
In the phase 3 study, 358 patients with resectable stage IB (≥4 cm) to IIIA NSCLC lacking EGFR or ALK alterations were randomly assigned to receive three cycles of platinum-doublet chemotherapy with or without nivolumab 360 mg every 3 weeks.
At a minimum follow-up of 21 months, the co-primary endpoint of EFS (the other being pCR) was a median of 31.6 months for the nivolumab plus chemotherapy group and 20.8 months for the chemotherapy alone group. This corresponded to a significant reduction in the risk for disease progression, recurrence, or death of 37% in favor of the PD-1 inhibitor.
The estimated 1-year EFS rates were 76.1% with nivolumab and 63.4% without nivolumab, while the respective 2-year rates were 63.8% and 45.3%.
Patrick Forde (Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA) and co-investigators highlight that the EFS benefit afforded by nivolumab was observed “across most key subgroups.”
But “the magnitude of benefit was greater in patients with stage IIIA disease than in those with stage IB or II disease […], in patients with a tumor PD-L1 expression level of 1% or more than in those with a level of less than 1%, and in patients with a nonsquamous histologic type than in those with a squamous histologic type,” they continue.
At the first interim analysis for overall survival, the median was not reached in either treatment group but there was “a potential trend in favor of nivolumab plus chemotherapy,” say the researchers, adding that “[c]ontinued follow-up is required for data on overall survival to mature.”
Reporting on the safety profile, they say that “[t]reatment with nivolumab plus chemotherapy did not result in a higher incidence or greater severity of adverse events [AEs] than chemotherapy alone,” nor did the addition of nivolumab lead to an increase in “surgery-related adverse events or impede the feasibility of surgery.”
The author of a related editorial says that the “[r]esults from this trial are expected to be practice changing, as evidenced by the FDA approval of neoadjuvant nivolumab plus chemotherapy.”
But she highlights several issues such as whether pCR is predictive of EFS and whether EFS is a valid surrogate for overall survival, as well as the need for a multidisciplinary approach to administer neoadjuvant therapy, “which may be challenging in some centers.”
Nevertheless, Christine Lovly (Vanderbilt University Medical Center, Nashville, Tennessee, USA) concludes: “[A]lthough challenges remain, broad implementation of neoadjuvant therapy is expected to herald a new era for lung cancer, coupling innovative treatments supported by a strong biologic rationale with timely assessment of antitumor responses in order to deliver on the promise of a decreased incidence of lung cancer–related death among patients with early-stage disease.”
These results were presented simultaneously at the AACR Annual Meeting 2022 in New Orleans, Louisiana, USA.
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AACR Annual Meeting 2022; New Orleans, Louisiana, USA: 8–13 April
N Engl J Med 2022; doi:10.1056/NEJMoa2202170
N Engl J Med 2022; doi:10.1056/NEJMe2203330